Klebsiella species (K. pneumoniae, K. oxytoca, K. ozaenae and K. rhinoscleromatis)
Table 1. Susceptibility of K. pneumoniae to Antimicrobial Agents.
0.5 - >12
Penicillins plus beta-lactamase inhibitors
0.25 - 8
1 - 256
2 - >16
≤8 – >64
First generation cephalosporins
8 - 64
4 - 32
4 - 128
Second generation cephalosporins
2 - >32
0.5 - 128
0.5 - 64
0.12 - 32
1 - 32
1 - 16
0.12 - >32
0.5 - 16
Third generation cephalosporins
0.016 - >128
0.25 - >32
0.016 - 0.5
0.12 - 32
0.06 - 1
< 0.06 - >32
0.06 - >32
< 0.015 - >32
0.5 - >32
Table 1a. Susceptibility of K. pneumoniae to Antimicrobial Agents (continued)
<4 - >8
≤1 to >8
0.06 - 32
0.12 - 2
0.12 - .500
0.008 - 0.03
0.06 - 2
0.03 - 2
0.03 - 2
≤0.5 - >4
0.03 - 2
0.06 - 2
0.03 - >32
0.016 - 1
<0.03 - >16
0.03 - >16
0.005 - >25
0.12 - 500
0.125 - 16
NS = Not specified
Collated from the references 21, 26, 29, 30, 48, 92, 95, 96, 103, 127, 128,148, 175, 239, 279,
Table 2. Susceptibility of ESBL Producing K. pneumoniae to Antimicrobial Agents.
16 – 256
Penicillins plus beta-lactamase inhibitors
Amoxicillin - Clavulanate
Ticarcillin - Clavulanate
Ampicillin - Sulbactam
Piperacillin - Tazobactam
Cefotaxime - Clavulanate
Ceftazidime - Clavulanate
Cefotaxime - Sulbactam
16 - >64
8 - >128
0.5 - >128
0.25 - 2
0.06 - 2
0.25 – 32
First generation cephalosporins
16 – 512
Second generation cephalosporins
16 - 512
4 - 64
0.03 – 64
Third generation cephalosporins
0.03 - 256
4 - 64
0.25 - 512
0.25 - >128
0.25 – 128
Table 2a. Susceptibility of ESBL Producing K. pneumoniae to Antimicrobial Agents (continued)
Other beta lactams
0.06 – >8
0.016 - 2
0.25 - 512
0.05 - >16
0.12 - >8
Molecular epidemiology of Klebsiella variicola obtained from different sources
Klebsiella variicola is considered an emerging pathogen in humans and has been described in different environments. K. variicola belongs to Klebsiella pneumoniae complex, which has expanded the taxonomic classification and hindered epidemiological and evolutionary studies. The present work describes the molecular epidemiology of K. variicola based on MultiLocus Sequence Typing (MLST) developed for this purpose. In total, 226 genomes obtained from public data bases and 28 isolates were evaluated, which were mainly obtained from humans, followed by plants, various animals, the environment and insects. A total 166 distinct sequence types (STs) were identified, with 39 STs comprising at least two isolates. The molecular epidemiology of K. variicola showed a global distribution for some STs was observed, and in some cases, isolates obtained from different sources belong to the same ST. Several examples of isolates corresponding to kingdom-crossing bacteria from plants to humans were identified, establishing this as a possible route of transmission. goeBURST analysis identified Clonal Complex 1 (CC1) as the clone with the greatest distribution. Whole-genome sequencing of K. variicola isolates revealed extended-spectrum β-lactamase- and carbapenemase-producing strains with an increase in pathogenicity. MLST of K. variicola is a strong molecular epidemiological tool that allows following the evolution of this bacterial species obtained from different environments.
The Klebsiella genus, a member of the family Enterobacteriaceae, comprises species found in diverse environmental niches. In fact, using phylogenetic reconstruction methods, Klebsiella pneumoniae has been divided into five distinct species. Klebsiella variicola was first described in 20041, followed by the identification Klebsiella quasipneumoniae in 2014 (with two subspecies; K. quasipneumoniae subsp. quasipneumoniae and K. quasipneumoniae subsp. similipneumoniae)2, Klebsiella quasivariicola (which remains to be validated) in 20173. Finally in 2019 Klebsiella africanensis a new bacterial species and a subspecies of K. variicola; named, Klebsiella variicola subsp. tropicalensis were described4. The description of these new bacterial species has expanded the taxonomic classification of the genus Klebsiella, which are described as the Klebsiella pneumoniae complex5. Since K. variicola was described several international reports have discussed its importance6; indeed, it is considered an emerging pathogen in humans7. Similar to other Klebsiella species, K. variicola is a gram-negative, facultative anaerobic, nonspore-forming, nonmotile rod-shaped bacteria that forms circular, convex, and smooth colonies8. K. variicola was initially identified as an endophyte in plants and as a pathogen in humans1. In addition, K. variicola is considered a symbiont in insects, a pathogen in animals and plants. Moreover, K. variicola has been identified in several environmental sources6,9,10,11. As a human pathogen, K. variicola has been isolated from diverse clinical samples, including the blood, tracheal aspirates, several types of secretions, the respiratory and urinary tract infections, and surgical wounds7. The estimated prevalence of K. variicola is highly variable: initially, a prevalence of 8% was reported1, which has varied over time from 1.8% to 24.4% in clinical settings12,13,14. The highest percentage reported to date is 24.4%, which were obtained from bloodstream infections in a University Hospital in Solna, Sweden14. The prevalence of the species complex is variable, mainly due to misclassification problems13.
Members of the K. pneumoniae complex share biochemical and phenotypic features. This has led to misclassification by conventional methods and several cases of K. variicola misidentified as K. pneumoniae and in a few cases as K. quasipneumoniae; K. quasipneumoniae has also been misidentified as K. variicola15,16. K. pneumoniae being the most prevalent species within the complex4,13,17, however, regarding urinary tract infections, K. variicola has been isolated more frequently unlike K. pnuemoniae and K. quasipneumoniae18.
Phylogenetic analysis of the Klebsiella genus, the rpoB gene has been recommended for the proper differentiation of this genus19, even though both the 16S rRNA and rpoB genes have been used for this purpose14,20. The K. variicola strain DX120E was identified using these genes, with rpoB showing a higher level of accuracy21. As correct identification of K. variicola using phylogenetic analysis requires time and trained personnel, thus, several biochemical and basic molecular methods have been explored. The biochemical method using adonitol was not effective, generating false positives22. Nonetheless, several PCR methods have been developed to differentiate certain species of the Klebsiella genus12,23,24,25. In addition, the use of Matrix-Assisted Laser Desorption/Ionization-Time of Flight (MALDI-TOF) mass spectrometry to identify microorganisms has frequently been reported26. Despite initial difficulty in differentiating among members of this genus13,23, the MALDI-TOF approach has been recently optimized, particularly for the K. pneumoniae complex5.
Using PCR screening, phylogenetic analyses and whole-genome sequencing (WGS) methods, K. variicola has recently been identified in diverse niches with clinical and environmental importance6,7,15. These efforts to identify and characterize a significant number of K. variicola isolates have prompted studies of their molecular characterization and epidemiology. The present study describes the molecular epidemiology of K. variicola using Multilocus Sequence Typing (MLST), developed for this purpose. This study identified broad dissemination of K. variicola isolates obtained from different regions of the world and a considerable number of ESBL- and carbapenemase-producing isolates were identified. Likewise, a possible pandemic clone was identified and the notion of kingdom-crossing bacteria from plants to humans, establishing this as a route of transmission for K. variicola.
Results and Discussion
The K. variicola genomes were acquired from public databases, which were collected from various sources in several countries of the five continents. The isolates include from plants, insects, the environment, animals, and a significant number of isolates were obtained from human samples (Supplementary Dataset). Based on 33 K. variicola genomes, the AMPHORA program identified a set of 31 phylogenetic marker genes. Among these genes, rpoB, phoE, nifH, mdh, and infB were previously considered for phylogenetic analysis in K. variicola1, and six genes (phoE, tonB, rpoB, mdh, infB, and gapA) are included in the K. pneumoniae MLST27. In addition, concatenation of fusA, gapA, gyrA, leuS and rpoB has been proposed for the proper phylogenetic differentiation of K. pneumoniae, K. variicola and K. quasipneumoniae2. The genes gyrA, nifH and tonB were eliminate due to they may be subjected to selection bias either by the use of antimicrobial agents28, nitrogen fixation1,29,30 or binding and transport of ferric chelates31, respectively. Finally, leuS (leucyl-tRNA synthetase), pgi (phosphoglucose isomerase), pgk (phosphoglycerate kinase), phoE (phosphoporine E), pyrG (CTP synthase), rpoB (β-subunit of RNA polymerase B) and fusA (elongation factor G) were selected for K. variicola MLST scheme (Table 1) (http://mlstkv.insp.mx) and for the assignation of sequence types (ST) (Supplementary Dataset). Of note, the pyrG (CTP synthase class I) gene is not present in K. pneumoniae genomes, which was verified using a BLASTn genome search and confirmed by PCR of several K. pneumoniae clinical isolates in our collection (data not shown). The primer sequences, amplified fragments, number of alleles, nucleotide diversity and polymorphic sites of each of the seven genes are described in Table 1.
Considering K. variicola isolate 801 obtained from a pediatric outbreak in Mexico32 as ST1 (Supplementary Dataset), and the MLST was applied arbitrarily to K. variicola genomes and isolates include in the study. A total of 166 distinct sequence types (STs) were identified among 254 K. variicola genomes and isolates obtained from different sources, such as humans, plants, insects, the environment and animals. From 166 STs, 39 STs were shared by at least two isolates (Fig. 1 and Supplementary Dataset).
The global distribution of STs is shown in Fig. 1. The major number of isolates assigned to an ST were from the USA, followed by Mexico, China and Europe (mainly Germany). In the case of the USA, numerous isolates with the same ST were also identified in other regions of the world (Supplementary Dataset). In particular, Klebsiella WGS projects have been performed in the USA, the first was carried out by the Houston Methodist Hospital, Texas13 and the second from the Barnes-Jewish Hospital microbiology laboratory in Missouri18. In both cases, numerous K. variicola isolates were identified, with ST49, ST51, ST73, ST75 and ST77 described in both works (Fig. 1 and Supplementary Dataset).
With respect to Mexico, ST1 corresponds to the first pediatric outbreak of K. variicola32 and other isolates obtained from the USA (WUSM_KV_09)18. In addition, this country contributed the most isolates obtained from different plants (Fig. 1). Overall, human isolates are heterogeneous regarding STs, and only ST32 was identified for two human isolates. Nevertheless, the ST37 and ST41 contains isolates from Mexico, USA and Singapore. In China, isolates from both humans and plants have been described, with ST65 and ST92 corresponding to human isolates described in different reports (Fig. 1 and Supplementary Dataset). The BioProject-PRJEB10018 includes Klebsiella isolates from European countries and identified numerous K. variicola human isolates. These isolates showed heterogeneous STs, with only ST144 (Hungary and Portugal) and ST146 (Ireland and United Kingdom) having the same ST. However, countries in different regions of the world harbor the same STs (ST3, -20, -32, -37, -68, -77, -86, -105 and -125) of isolates described in Europe.
In particular, some STs are highlighted, such as ST10 identified in Denmark, China, Tanzania and the USA. ST11 isolates obtained from plants originate from Mexico and China. Nine human isolates obtained from Germany, Belgium and the USA were identified as ST2018, and ST56 and ST57 were found on distant continents such as North America, Europe and Australia, all from human samples. ST60 corresponds to the second pediatric outbreak of K. variicola described in Bangladesh33 and ST64 to K. variicola obtained from the environment in South Korea10.
Interestingly, three cases of kingdom-crossing bacteria (KCB) were identified by MLST. ST3 was identified in a plant (banana roots) isolate in Mexico and human isolates from Italy and Serbia. ST16 was identified in isolates obtained from a chili plant in Malaysia and humans in the USA. ST62 corresponds to a well-characterized K. variicola D5A isolate obtained from plants in China34 and ID_24 isolates obtained from humans in Germany. The proposal of KCB from plants to humans, which may indicate a process of transfer known as phytonosis, has been described previously29. K. variicola clinical isolate X39 is considered a KCB because it contains genes involved in plant colonization, nitrogen fixation, and defense against oxidative stress; this isolate is also considered an endophytic bacterium based on its capacity to colonize maize35.
K. variicola MLST allowed us to analyze the allelic profile of the K. variicola isolates included in this study using the goeBURST algorithm. Figure 2 shows the sequence types of major isolates and ST relatedness. A total of 166 STs were identified from among the 254 isolates included in this study, and 127 are unique. The founder ST10 and ST23, ST38 and ST130 with a single locus variants (SLVs) comprise Clonal Complex 1 (CC1). ST10 corresponds to one of the most predominant STs, representing 70% of all strains in CC1 (7/10). Moreover, all CC1 strains have a human origin, and they were obtained from five different countries (China, Denmark, Mexico, Tanzania and the USA). In addition to CC1, other 12 SLVs (42 isolates) were identified by goeBURST analysis and only three SLV were from the same country. Approximately 85% of the SLVs were isolated from humans, 9% from the environment and 5% from plants. None of these SLVs from plants or the environment share a relationship. All STs described above present an SLV relationship, without sharing a clear common origin or country. The same heterogeneity was observed for 17 double locus variants (DLVs) (40 isolates) (Fig. 2).
K. variicola isolates obtained from different sources are suggested to be derived from a common genetic pool, without segregation between isolates from these sources13,36. In addition, Potter et al.18 reveal two distant lineages among K. variicola genomes using phylogenetic analysis of the core genome. In this study, the phylogenetic analysis was carried out using the seven concatenated genes from K. variicola MLST (Fig. 3). Similarity to previous works, showed not segregate isolates with regard to origin of the sample and the distant lineage was formed by the same K. variicola KvMx2 and YH43 isolates obtained from sugarcane and potato plants, respectively. In addition, in this distant lineage also grouped the K. variicola 11446 isolate obtained from humans (Fig. 3). The YH43 isolate is another case of misclassification of K. variicola, which was described as K. pneumoniae37.
The isolates obtained from public data bases were mostly obtained from humans (84.6%), followed by plants (7.0%), animals (3.5%), the environment (3.1%), insects (0.7%) and unknown or missing origin (0.7%). Clusters that corresponds to isolates of the same ST and KCB were revealed by phylogenetic analysis (only the most representatives are indicated in the Fig. 3). Isolates from human and plants phylogenetically related and that may be correspond KCBs are showed; these isolates are as follows: 11226 and CFN2006; L18, EuSCAPE_SI024, BIDMC90 and KvMx18; EuSCAPE_IT309 and KV321; AJ292 and B1; 342, 1565/2503 and KvMx4; WUSM_KV_02 and T29A and YH43 and 11446. Moreover, the At-2231 and KP5-138 isolates obtained from insects, together with the VI isolates from plants1, are phylogenetically related. However, MB351 obtained from the environment (industrial effluent), EuSCAPE_DE060 and EuSCAPE_GR014 from humans and QMP_B2_288 from an animal (bovine) are phylogenetic related. Interestingly, isolates 11248 and LMG23571 obtained from humans and the environment in Mexico and Singapore, respectively, belong to ST41 (Supplementary Dataset and Fig. 1).
The molecular epidemiology of ESBL- and carbapenemase-producing K. variicola isolates were explored using published data and for unpublished genomes the acquisition of resistance to β-lactam antibiotics due to β-lactamases was determined in silico (Fig. 4) (see Material and Methods). ESBL-producing isolates belong to ST1 (8/9 isolates), ST4, ST10 (2/7 isolates), ST14, ST57 (1/2 isolates), ST60 (6/11), ST64 (1/3 isolates), ST65 (2/2 isolates), ST69, ST72, ST74, ST76, ST77 (1/2 isolates), ST78 (1/2 isolates), ST92 (3/4 isolates), ST94, ST125 (1/2 isolates), ST130, ST160 and ST164. ESBLs SHV-type and CTX-15 were the most prevalent (Fig. 4 and Supplementary Dataset). Several ST described above also are carbapenemase-producing isolates, which have been described in different countries. In the USA, ST53, ST61, ST75, ST125 and ST130 were found to be KPC-2 producers and, in some cases, in combination with ESBL SHV- or CTX-M-type strains. Similarly, ST76 produces NDM-1 and CTX-M-15. Another carbapenemase-producing K. variicola isolates on the American continent are ST71 with KPC-2. In Europe, ST136 with KPC-2 has been reported. In Asian countries, ST60 corresponds to the pediatric outbreak in Bangladesh and is composed of CTX-M-15 and NDM-1 producers and the ST69 in this country produces ESBLs and KPC-2. In South Korea, ST64 obtained from river water was positive for NDM-9 and CTX-M-65 in some isolates. Regarding China, ST92 and ST93 produce KPC-2 and NDM-5, in combination with CTX-M-15 for ST93. Half of the isolates described as carbapenemase-producing also were positive for ESBLs of TEM-, SHV- or CTX-M-type families (Fig. 1 and Supplementary Dataset).
Although no WGS data are available in two reports of carbapenemase-producing K. variicola isolates39,40, we would like to highlight these studies because they correspond to the first descriptions of carbapenemase-producing K. variicola isolates. The plasmid-borne carbapenemase genes identified were OXA-181 and IMI-2, from Switzerland and the United Kingdom, respectively.
Currently, accurate differentiation of K. pneumoniae, K. quasipneumoniae, K. variicola and K. quasivariicola is not routinely performed in the clinical setting. The main reason is the lack of implementation of the methods available in clinical or research laboratories41. Therefore, any of the K. quasipneumoniae, K. variicola and K. quasivariicola isolates are continuously misclassified as K. pneumoniae. The clinical importance of K. variicola is overshadowed by inaccurate identification, and thus, the actual prevalence has also been underestimated. Initially, correctly identified K. variicola was achieved by phylogenetic analysis mainly using the rpoB gene. However, several molecular approaches have been proposed to properly detect these species12,23,24, and MALDI-TOF identification of these species has been improved5. In addition, one-step PCR amplification of chromosomal β-lactamases of K. pneumoniae, K. quasipneumoniae and K. variicola for identification should be considered carefully. Long et al.13 identified a rare recombinant of the OKP/LEN core genes. In the present work, the LEN-type gene was found in 98.8% of the K. variicola genomes, whereas the other 1.2% of the genomes lacked for LEN-type chromosomal β-lactamase (Supplementary Dataset), a fact that should be considered when chromosomal β-lactamase genes are used for species identification. Nevertheless, at the genomic level, misclassifications among K. pneumoniae, K. quasipneumoniae and K. variicola have recently been rectified15. An excellent option at the genomic level is ANI, a tool proposed for the correct identification of bacterial species15,42,43. Overall, the increasing number of options for differentiating K. variicola from closely related species in the K. pneumoniae complex increases the number of isolates, and more WGS projects for this bacterial species will likely be conducted in the near future.
Considering the findings described above, the ANI tool was implemented in our MLST scheme for K. variicola (http://mlstkv.insp.mx) for correct identification of bacterial species using WGS data. These WGS data is compared with the reference genomes of K. pneumoniae, K. quasipneumoniae, K. variicola and K. quasivariicola, and once ANI confirme that the genome correspond to K. variicola (>95%), the ST is assigned according to the K. variicola MLST database. If Klebsiella sp. genomes were found to be <95% homologous, then they are not assigned an ST, and the platform determine whether the species correspond to any of the other species included in the ANI analysis. In addition, if MLST for K. variicola is implemented in laboratories interested in determining STs among K. variicola isolates, the isolates negative for pyrG by PCR amplification suggest the possibility that these isolates do might not correspond to K. variicola.
Figure 5 depicts the epidemiological history of K. variicola based on the year of publication. Although the first three works related to K. variicola were published in 2001, 2004 and 2008, the bacteria identified were isolated in the previous years. An outbreak of K. variicola was described in 2007, but the isolates were obtained in 199633. These isolates are related to bloodstream infections from a pediatric outbreak in Mexico. The first K. variicola isolate (801) was obtained on April 09 of 1996 (Fig. 5). Subsequently, this isolate was subjected to WGS and used to develop a PCR-multiplex assay12 and considered as ST1 in this work. To describe K. variicola as a new bacterial species in 20041, a phylogenetic analysis that included K. pneumoniae isolates identified three phylogroups, named KpI, KpII and KpIII, was described in 200144. The KpIII phylogroup was mentioned by Rosenblueth et al. (2004), which corresponds to K. variicola1. In the next year (2005), several isolates belonging to the KpIII group and obtained from veterinary infections (dog, monkey and bird) in the Netherlands also correspond to K. variicola45. The first K. variicola misclassification corresponded to K. pneumoniae 342, and several reports subsequently described this isolate as K. variicola. One year later, K. variicola At-22 was obtained from leaf-cutter ant-fungus gardens in South America31, and numerous K. variicola genomes have since been described (Fig. 5). Several studies have considered the misclassification existing within the Klebsiella genus12,13,15,16 it has allowed that genomes that correspond to K. variicola could be correctly identified and updated. The population structure, virulence and antibiotic resistance of K. variicola has been addressed through WGS34, and the BioProject (PRJEB10018) recently identified K. variicola clinical isolates in several European countries (Fig. 1). In general, rigorous molecular epidemiological studies of K. variicola require an MLST scheme, which allow for surveillance of multidrug-resistant and hypervirulent clones.
Comparison of MLST schemes
The K. pneumoniae MLST scheme works for K. variicola and different studies have applied the K. pneumoniae MLST scheme for typing K. variicola isolates13,14,18. However, for an unknown reason, a large number of K. variicola isolates were not assigned an ST, considering that the genomes have been determined13,18. In this study, both MLST schemes were compared using K. variicola genomes.
K. pneumoniae MLST was developed in 2005, when new species closely related to K. pneumoniae were still unknown. Of the seven locus (rpoB, gapA, mdh, pgi, phoE, infB and tonB) of the K. pneumoniae MLST scheme, three (rpoB, pgi and phoE) are shared with the K. variicola MLST scheme. The tonB was not considered for K. variicola MLST because in the case of K. pneumoniae, several nucleotides have been inserted at this locus. However, the K. pneumoniae MLST scheme eliminates inserted nucleotides (https://bigsdb.pasteur.fr/klebsiella/klebsiella.html). Such nucleotide insertion was also identified in the tonB gene of K. variicola. Considering its role in the binding and transport of siderophores, tonB might be undergoing selection pressure. These proteins could be directly involved in pathogenicity46, which has been observed an increase in pathogenicity for Klebsiella spp., with strains of K. pneumoniae, K. quasipneumoniae and K. variicola being hypervirulent35,47,48,49. Further investigation is needed to this respect.
In the case of rpoB, leuS and fusA and pyrG genes were considered in the K. variicola MLST scheme, because the first three genes were proposed for phylogenetic differentiation of K. pneumoniae, K. variicola and K. quasipneumoniae2. In the case of pyrG, a GTP synthase class-I is absent in K. pneumoniae and as mentioned above, this gene may contribute to the proper identification of K. variicola.
Moreover, 178 of the K. variicola genomes included in this study were subjected to ST assignments in the K. pneumoniae MLST scheme, of them 11.8% of the genomes were not assigned to an ST because they corresponded to new ones. K. variicola genomes with an assigned ST were analyzed through goeBURST analysis using the K. pneumoniae MLST database. This result showed a clear dispersion of K. variicola isolates, considering that the STs assigned to K. variicola isolates are shared ST profile with the K. pneumoniae isolate deposited in the K. pneumoniae MLST database (Fig. S1). However, the goeBURST analysis using the K. variicola MLST database revealed that some of these K. variicola isolates are close related to each other when they were separated by an SLV. These data emphasize that it is difficult to establish genetic relationships among K. variicola isolates using the K. pneumoniae MLST scheme because K. variicola isolates are related to those of K. pneumoniae instead of those of their own species. In summary, using the same MLST scheme for closely related bacterial species is not discriminative.
Finally, the allelic profile of K. variicola genomes was analyzed using both K. pneumoniae and K. variicola MLST schemes (Fig. S2). A heatmap shows higher variability when the K. variicola MLST scheme was applied in the examined K. variicola genomes.
Impact of K. variicola in different environments
In the last year, K. variicola has been strongly suggested to cause serious infections in humans, including hospital outbreaks, which has increased the phenotypic identification of ESBL- and carbapenemase-producing in environmental and clinical isolates. An increase in virulence has also been described, including the identification of hypermucoviscous50 and hypervirulent33 strains and those causing high mortality in a pediatric outbreak51. Additionally, colistin-resistant isolates have been reported, and the chromosomal mechanisms that are responsible for this phenotype have been identified35. Outside the clinical environment, signs of infection in farm and wild animals have been observed and strongly correlated with some insects. K. variicola is widely distributed among different groups of plants, mainly those consumed by humans, which facilitates the transfer of these bacteria from plants to humans. Accordingly, K. variicola species has been proposed to constitute a cross-kingdom bacterium. In the environment, K. variicola has been detected in rivers and on inert surfaces, and a review of K. variicola details the wide range of environments in which K. variicola has been detected as well as its use in industry6. In addition to the nitrogen-fixation capacity of K. variicola, these findings reveal clear differences from other species of the Klebsiella genus, mainly K. pneumoniae8,16,17,29.
K. variicola is a bacterial species that has been misclassified as K. pneumoniae for years, and it has also been misclassified as K. quasipneumoniae. K. variicola and K. pneumoniae share clinical settings and both are endophytes in plants and cause infections in livestock and wild animals. In clinical settings, K. variicola shows clear differences with regard to infection, highlighting the importance of early diagnosis. There are several approaches for the proper identification of K. variicola among K. pneumoniae complex. The database of K. variicola MLST will allow the molecular epidemiology of this bacterial species and establish the identification of possible pandemic clones. In addition, this study reveals a possible route of transmission of this bacterial endophyte from plants to humans. Although this phenomenon was previously identified, several results of the present study strengthen this evidence. K. variicola and K. pneumoniae are closely related bacterial species which must be stored separately, preventing one from masking the other and the relationships among the same bacterial species can being found.
Materials and Methods
K. variicola MLST scheme
For the development of the K. variicola MLST scheme, seven housekeeping genes were selected after AMPHORA (AutoMated PHylogenOmic infeRence) analysis51. The analysis was performed using thirty-three K. variicola proteomes. Primer pairs were successfully designed (using the Primer-BLAST tool https://www.ncbi.nlm.nih.gov/tools/primer-blast/) for PCR amplification and sequencing of an internal position of the seven genes.
K. variicola genomes
In total, 226 K. variicola genomes were obtained from public GenBank/ENA databases (01/05/2019). These genomes were validated as belonging to K. variicola using the Average Nucleotide Identity (ANI) tool45. The reference genomes for each bacterial species included are K. pneumoniae MGH78578 (GenBank Accession number CP000647.1), K. quasipneumoniae 18A069 (GenBank Accession number CBZM000000000), K. variicola At22 (GenBank Accession number CP001891.1) and K. quasivariicola KPN1705 (GenBank Accession number CP022823.1).
Sequence type determination in K. variicola genomes and isolates
K. variicola MLST scheme STs were determined for 226 K. variicola genomes and a collection of 28 K. variicola isolates obtained from plants and humans in Mexico. In these isolates, the PCR amplification products were carried out following the instructions described in this study (Table 1). The nucleotide sequences of the 7 MLST genes were obtained using BigDyeTM Terminator v3.1 and analyzed with the Applied Biosystems 3130 platform. For more details of the PCR conditions visit the page of K. variicola MLST scheme (http://mlstkv.insp.mx).
The goeBURST-1.2.152 program was used to analyze STs of K. variicola isolates and to assign isolates to a clonal complex (CC). A clonal complex is defined as a set of similar STs with six identical locus. A CC is formed by the founder ST and its SLVs.
The phylogenetic analysis was performed using the 7-locus K. variicola MLST concatenated genes, and a Maximum Likelihood phylogeny tree was generated using Mega software v7.0.26. The Tamura-Nei model with discrete Gamma distribution was applied to model evolutionary rate differences among sites (4 categories (+G, parameter = 0.1133))53.
Implementation of ANI by proper K. variicola bacterial species
ANI tool45 analysis was implemented in the K. variicola MLST homepage (http://mlstkv.insp.mx) to ensure the correct identification of K. pneumoniae, K. quasipneumoniae, K. variicola and K. quasivariicola. The reference genomes for each bacterial species analyzed using ANI are K. pneumoniae MGH78578 (GenBank Accession number CP000647.1), K. quasipneumoniae 18A069 (GenBank Accession number CBZM000000000), K. variicola At22 (GenBank Accession number CP001891.1) and K. quasivariicola KPN1705 (GenBank Accession number CP022823.1).
Molecular epidemiology of K. variicola
The molecular epidemiology of susceptible, ESBL- and carbapenemase-producing K. variicola was established according to respective publications (Supplementary Dataset). In addition, isolates with genomic data but unpublished β-lactamases were determined using ResFinder based on acquired antimicrobial resistance genes (https://cge.cbs.dtu.dk/services/ResFinder/)54.
Comparison of MLST typing schemes
The MLST K. pneumoniae scheme was used to determine STs for 178 K. variicola genomes included in the study. goeBURST analysis was carried out using the allelic profile. A heatmap was drawn to determine the distances between the allelic profiles of the seven genes of the K. pneumoniae and K. variicola MLST schemes and Multiple Experiment Viewer MeV version 4.8.1 software.
Rosenblueth, M., Martinez, L., Silva, J. & Martinez-Romero, E. Klebsiella variicola, a novel species with clinical and plant-associated isolates. Syst. Appl. Microbiol.27, 27–35 (2004).
CASArticle Google Scholar
Brisse, S., Passet, V. & Grimont, P. A. Description of Klebsiella quasipneumoniae sp. nov., isolated from human infections, with two subspecies, Klebsiella quasipneumoniae subsp. quasipneumoniae subsp. nov. and Klebsiella quasipneumoniae subsp. similipneumoniae subsp. nov., and demonstration that Klebsiella singaporensis is a junior heterotypic synonym of Klebsiella variicola. Int. J. Syst. Evol. Microbiol.64, 3146–3152 (2014).
Article Google Scholar
Long, S. W. et al. Whole-Genome Sequencing of a Human Clinical Isolate of the Novel Species Klebsiella quasivariicola sp. nov. Genome Announc. 5 (2017).
Rodrigues, C. et al. Description of Klebsiella africanensis sp. nov., Klebsiella variicola subsp. tropicalensis subsp. nov. and Klebsiella variicola subsp. variicola subsp. nov. Res. Microbiol (2019).
Rodrigues, C., Passet, V., Rakotondrasoa, A. & Brisse, S. Identification of Klebsiella pneumoniae, Klebsiella quasipneumoniae Klebsiella variicola and Related Phylogroups by MALDI-TOF Mass Spectrometry. Frontiers in Microbiology9, 1–7 (2018).
Article Google Scholar
Duran-Bedolla, J., Garza-Ramos, U., Rodriguez-Medina, N., Aguilar-Vera A. & Barrios-Camacho, H. Klebsiella variicola: a pathogen and eco-friendly bacteria with applications in biolgical and industrial processes. Applied and Environmental Microbiology. under review (2019).
Rodriguez-Medina, N., Barrios-Camacho, H., Duran-Bedolla, J. & Garza-Ramos, U. Klebsiella variicola: an emerging pathogen in humans. Emerging Microbes and Infectious. 8, 973-988 (2019).
Lin, L. et al. Complete genome sequence of endophytic nitrogen-fixing Klebsiella variicola strain DX120E. Stand. Genomic. Sci.10, 22 (2015).
Article Google Scholar
Afzal, A. M., Rasool, M. H., Waseem, M. & Aslam, B. Assessment of heavy metal tolerance and biosorptive potential of Klebsiella variicola isolated from industrial effluents. AMB. Express7, 184 (2017).
Article Google Scholar
Di, D. Y., Jang, J., Unno, T. & Hur, H. G. Emergence of Klebsiella variicola positive for NDM-9, a variant of New Delhi metallo-beta-lactamase, in an urban river in South Korea. J. Antimicrob. Chemother.72, 1063–1067 (2017).
CASPubMed Google Scholar
Gomi, R. et al. Characteristics of Carbapenemase-Producing Enterobacteriaceae in Wastewater Revealed by Genomic Analysis. Antimicrob. Agents Chemother. 62 (2018).
Garza-Ramos, U. et al. Development of a multiplex-PCR probe system for the proper identification of Klebsiella variicola. BMC. Microbiol.15, 64 (2015).
Article Google Scholar
Long, S. W. et al. Whole-Genome Sequencing of Human Clinical Klebsiella pneumoniae Isolates Reveals Misidentification and Misunderstandings of Klebsiella pneumoniae, Klebsiella variicola, and Klebsiella quasipneumoniae. mSphere. 2 (2017).
Maatallah, M. et al. Klebsiella variicola is a frequent cause of bloodstream infection in the stockholm area, and associated with higher mortality compared to K. pneumoniae. PLoS. One.9, e113539 (2014).
ADSArticle Google Scholar
Martinez-Romero, E. et al. Genome misclassification of Klebsiella variicola and Klebsiella quasipneumoniae isolated from plants, animals and humans. Salud Publica Mex.60, 56–62 (2018).
Article Google Scholar
Chen, M. et al. Genomic identification of nitrogen-fixing Klebsiella variicola, K. pneumoniae and K. quasipneumoniae. J. Basic Microbiol.56, 78–84 (2016).
CASArticle Google Scholar
Holt, K. E. et al. Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae, an urgent threat to public health. Proc. Natl. Acad. Sci. USA112, E3574–E3581 (2015).
CASArticle Google Scholar
Potter, R. F. et al. Population Structure, Antibiotic Resistance, and Uropathogenicity of Klebsiella variicola. MBio. 9 (2018).
Martinez, J., Martinez, L., Rosenblueth, M., Silva, J. & Martinez-Romero, E. How are gene sequence analyses modifying bacterial taxonomy? The case of Klebsiella. Int. Microbiol.7, 261–268 (2004).
CASPubMed Google Scholar
Seki, M. et al. Fatal sepsis caused by an unusual Klebsiella species that was misidentified by an automated identification system. J. Med. Microbiol.62, 801–803 (2013).
Article Google Scholar
Chun-Yan, W. et al. Endophytic nitrogen-fixing Klebsiella variicola strain DX120E promotes sugarcane growth. Biology and Fertility of Soils50, 657–666 (2014).
Article Google Scholar
Alves, M. S., Dias, R. C., de Castro, A. C., Riley, L. W. & Moreira, B. M. Identification of clinical isolates of indole-positive and indole-negative Klebsiella spp. J Clin. Microbiol44, 3640–3646 (2006).
CASArticle Google Scholar
Berry, G. J., Loeffelholz, M. J. & Williams-Bouyer, N. An Investigation into Laboratory Misidentification of a Bloodstream Klebsiella variicola Infection. J. Clin. Microbiol.53, 2793–2794 (2015).
CASArticle Google Scholar
Fonseca, E. L. et al. A one-step multiplex PCR to identify Klebsiella pneumoniae, Klebsiella variicola, and Klebsiella quasipneumoniae in the clinical routine. Diagn. Microbiol Infect. Dis.87, 315–317 (2017).
CASArticle Google Scholar
Yasuhara-Bell, J., Ayin, C., Hatada, A., Yoo, Y. & Schlub, R. L. Specific detection of Klebsiella variicola and K. oxytoca by Loop-Mediated Isothermal Amplification. J Plant Pathol Microbiol6 (2015).
van Veen, S. Q., Claas, E. C. & Kuijper, E. J. High-throughput identification of bacteria and yeast by matrix-assisted laser desorption ionization-time of flight mass spectrometry in conventional medical microbiology laboratories. J. Clin. Microbiol.48, 900–907 (2010).
Article Google Scholar
Diancourt, L., Passet, V., Verhoef, J., Grimont, P. A. & Brisse, S. Multilocus sequence typing of Klebsiella pneumoniae nosocomial isolates. J. Clin. Microbiol.43, 4178–4182 (2005).
CASArticle Google Scholar
Zhao, X., Xu, C., Domagala, J. & Drlica, K. DNA topoisomerase targets of the fluoroquinolones: a strategy for avoiding bacterial resistance. Proc. Natl. Acad. Sci. USA94, 13991–13996 (1997).
ADSCASArticle Google Scholar
Martinez-Romero, E., Rodriguez-Medina, N., Beltran-Rojel, M., Toribio-Jimenez, J. & Garza-Ramos, U. Klebsiella variicola and Klebsiella quasipneumoniae with capacity to adapt to clinical and plant settings. Salud Publica Mex.60, 29–40 (2018).
Article Google Scholar
Pinto-Tomas, A. A. et al. Symbiotic nitrogen fixation in the fungus gardens of leaf-cutter ants. Science326, 1120–1123 (2009).
ADSCASArticle Google Scholar
Noinaj, N., Guillier, M., Barnard, T. J. & Buchanan, S. K. TonB-dependent transporters: regulation, structure, and function. Annu. Rev. Microbiol.64, 43–60 (2010).
CASArticle Google Scholar
Garza-Ramos, U., Martinez-Romero, E. & Silva-Sanchez, J. SHV-type extended-spectrum beta-lactamase (ESBL) are encoded in related plasmids from enterobacteria clinical isolates from Mexico. Salud Publica Mex.49, 415–421 (2007).
Article Google Scholar
Lu, Y., Feng, Y., McNally, A. & Zong, Z. Occurrence of colistin-resistant hypervirulent Klebsiella variicola. J. Antimicrob. Chemother.73, 3001–3004 (2018).
CASArticle Google Scholar
Liu, W. et al. Whole genome analysis of halotolerant and alkalotolerant plant growth-promoting rhizobacterium Klebsiella sp. D5A. Sci. Rep.6, 26710 (2016).
ADSCASArticle Google Scholar
Guo, Y. et al. Complete Genomic Analysis of a Kingdom-Crossing Klebsiella variicola Isolate. Front Microbiol.9, 2428 (2018).
Article Google Scholar
Fouts, D. E. et al. Complete genome sequence of the N2-fixing broad host range endophyte Klebsiella pneumoniae 342 and virulence predictions verified in mice. PLoS. Genet.4, e1000141 (2008).
Article Google Scholar
Iwase, T., Ogura, Y., Hayashi, T. & Mizunoe, Y. Complete Genome Sequence of Klebsiella pneumoniae YH43. Genome Announc. 4 (2016).
Medrano, E. G., Forray, M. M. & Bell, A. A. Complete Genome Sequence of a Klebsiella pneumoniae Strain Isolated from a Known Cotton Insect Boll Vector. Genome Announc. 2 (2014).
Zurfluh, K., Poirel, L., Nordmann, P., Klumpp, J. & Stephan, R. First detection of Klebsiella variicola producing OXA-181 carbapenemase in fresh vegetable imported from Asia to Switzerland. Antimicrob. Resist. Infect. Control4, 38 (2015).
CASArticle Google Scholar
Hopkins, K. L. et al. IMI-2 carbapenemase in a clinical Klebsiella variicola isolated in the UK. J. Antimicrob. Chemother.72, 2129–2131 (2017).
CASArticle Google Scholar
Fontana, L., Bonura, E., Lyski, Z. & Messer, W. The Brief Case: Klebsiella variicola-Identifying the Misidentified. J. Clin. Microbiol. 57 (2019).
Figueras, M. J., Beaz-Hidalgo, R., Hossain, M. J. & Liles, M. R. Taxonomic affiliation of new genomes should be verified using average nucleotide identity and multilocus phylogenetic analysis. Genome Announc. 2 (2014).
Goris, J. et al. DNA-DNA hybridization values and their relationship to whole-genome sequence similarities. Int. J. Syst. Evol. Microbiol.57, 81–91 (2007).
CASArticle Google Scholar
Brisse, S. & Verhoef, J. Phylogenetic diversity of Klebsiella pneumoniae and Klebsiella oxytoca clinical isolates revealed by randomly amplified polymorphic DNA, gyrA and parC genes sequencing and automated ribotyping. Int. J. Syst. Evol. Microbiol.51, 915–924 (2001).
CASArticle Google Scholar
Brisse, S. & Duijkeren, E. Identification and antimicrobial susceptibility of 100 Klebsiella animal clinical isolates. Vet. Microbiol.105, 307–312 (2005).
CASArticle Google Scholar
Russo, T. A. et al. Identification of Biomarkers for Differentiation of Hypervirulent Klebsiella pneumoniae from Classical K. pneumoniae. J. Clin. Microbiol. 56 (2018).
Breurec, S. et al. Liver Abscess Caused by Infection with Community-Acquired Klebsiella quasipneumoniae subsp. quasipneumoniae. Emerg. Infect. Dis.22, 529–531 (2016).
CASArticle Google Scholar
Farzana, R. et al. Outbreak of Hypervirulent Multi-Drug Resistant Klebsiella variicola causing high mortality in neonates in Bangladesh. Clin. Infect. Dis. (2018).
Shon, A. S., Bajwa, R. P. & Russo, T. A. Hypervirulent (hypermucoviscous) Klebsiella pneumoniae: a new and dangerous breed. Virulence.4, 107–118 (2013).
Article Google Scholar
Garza-Ramos, U. et al. Draft Genome Sequence of the First Hypermucoviscous Klebsiella variicola Clinical Isolate. Genome Announc. 3, (2015).
Wu, M. & Eisen, J. A. A simple, fast, and accurate method of phylogenomic inference. Genome Biol.9, R151 (2008).
Article Google Scholar
Feil, E. J., Li, B. C., Aanensen, D. M., Hanage, W. P. & Spratt, B. G. eBURST: inferring patterns of evolutionary descent among clusters of related bacterial genotypes from multilocus sequence typing data. J. Bacteriol.186, 1518–1530 (2004).
CASArticle Google Scholar
Kumar, S., Stecher, G. & Tamura, K. MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Datasets. Mol. Biol. Evol.33, 1870–1874 (2016).
CASArticle Google Scholar
Zankari, E. et al. Identification of acquired antimicrobial resistance genes. J. Antimicrob. Chemother.67, 2640–2644 (2012).
CASArticle Google Scholar
This work was supported by grant 256988 from SEP-CONACyT (Secretaría de Educación Pública-Consejo Nacional de Ciencia y Tecnología).
Humberto Barrios-Camacho and Alejandro Aguilar-Vera contributed equally.
Instituto Nacional de Salud Pública (INSP), Centro de Investigación Sobre Enfermedades Infecciosas (CISEI), Laboratorio de Resistencia Bacteriana, Cuernavaca, Morelos, Mexico
Humberto Barrios-Camacho, Marilu Beltran-Rojel, Josefina Duran-Bedolla, Nadia Rodriguez-Medina & Ulises Garza-Ramos
Universidad Nacional Autónoma de México, Centro de Ciencias Genómicas, Programa de Genómica Funcional de Procariotes, Cuernavaca, Morelos, Mexico
Instituto Nacional de Salud Pública (INSP), Centro de Información para Decisiones en Salud Pública (CENIDSP), Cuernavaca, Morelos, Mexico
Edgar Aguilar-Vera & Jesús Rojas
Universidad Nacional Autónoma de México, Centro de Ciencias Genómicas, Programa de Genómica Evolutiva, Cuernavaca, Morelos, Mexico
Luis Lozano-Aguirre & Olga Maria Perez-Carrascal
H.B.C. and A.A.-V. contributed equally to this work. U.G.-R., N.R.-M., H.B.-C., J.D.-B. and A.A.-V. contributed to analyzed the data and wrote the manuscript. H.B.-C., M.B.-R., O.M.P.-C. and J.D.-B. performed the experiments. A.A.-V., E.A.-V., J.R. and L.L.-A. developed the software. U.G.-R. contributed reagents/materials.
Correspondence to Ulises Garza-Ramos.
Klebsiella spp. as Nosocomial Pathogens: Epidemiology, Taxonomy, Typing Methods, and Pathogenicity Factors
1. Aguilar A, Merino S, Rubires X, Tomas J M. Influence of osmolarity on lipopolysaccharides and virulence of Aeromonas hydrophila serotype O:34 strains grown at 37°C. Infect Immun. 1997;65:1245–1250.[PMC free article] [PubMed] [Google Scholar]
2. Albertí S, Alvarez D, Merino S, Casado M T, Vivanco F, Tomás J M, Benedí V J. Analysis of complement C3 deposition and degradation on Klebsiella pneumoniae. Infect Immun. 1996;64:4726–4732.[PMC free article] [PubMed] [Google Scholar]
3. Albertí S, Marqués G, Camprubi S, Merino S, Tomás J M, Vivanco F, Benedí V J. C1q binding and activation of the complement classical pathway by Klebsiella pneumoniae outer membrane proteins. Infect Immun. 1993;61:852–860.[PMC free article] [PubMed] [Google Scholar]
4. Albesa I. Klebsiella pneumoniae haemolysin adsorption to red blood cells. J Appl Bacteriol. 1989;67:263–266. [PubMed] [Google Scholar]
5. Albesa I, Barberis L I, Pájaro M C, Eraso A J. Actividad hemolítica de Klebsiella pneumoniae sobre glóbulos rojos de conejo. Rev Latinoam Microbiol. 1985;27:83–87. [PubMed] [Google Scholar]
6. Albesa I, Barberis L I, Pajaro M C, Farnochi M C, Eraso A J. A thiol-activated hemolysin in gram-negative bacteria. Can J Microbiol. 1985;31:297–300. [PubMed] [Google Scholar]
7. Amako K, Meno Y, Takade A. Fine structures of the capsules of Klebsiella pneumoniae and Escherichia coli K1. J Bacteriol. 1988;170:4960–4962.[PMC free article] [PubMed] [Google Scholar]
8. Arlet G, Rouveau M, Casin I, Bouvet P J M, Lagrange P H, Philippon A. Molecular epidemiology of Klebsiella pneumoniae strains that produce SHV-4 β-lactamase and which were isolated in 14 french hospitals. J Clin Microbiol. 1994;32:2553–2558.[PMC free article] [PubMed] [Google Scholar]
9. Athamna A, Ofek I, Keisari Y, Markowitz S, S. D G G, Sharon N. Lectinophagocytosis of encapsulated Klebsiella pneumoniae mediated by surface lectins of guinea pig alveolar macrophages and human monocyte-derived macrophages. Infect Immun. 1991;59:1673–1682.[PMC free article] [PubMed] [Google Scholar]
10. Avorn J, Monane M, Gruwitz J H, Glynn J, Choodnovskiy I, Lipsitz L A. Reduction of bacteriuria and pyuria after ingestion of cranberry juice. JAMA. 1994;271:751–754. [PubMed] [Google Scholar]
11. Ayars G H, Altman L C, Fretwell M D. Effect of decreased salivation and pH on the adherence of Klebsiella species to human buccal epithelial cells. Infect Immun. 1982;38:179–182.[PMC free article] [PubMed] [Google Scholar]
12. Ayling-Smith B, Pitt T L. State of the art in typing: Klebsiella spp. J Hosp Infect. 1990;16:287–295. [PubMed] [Google Scholar]
13. Babu J P, Abraham S N, Dabbous M K, Beachey E H. Interaction of a 60-Kilodalton d-mannose-containing salivary glycoprotein with type 1 fimbriae of Escherichia coli. Infect Immun. 1986;54:104–108.[PMC free article] [PubMed] [Google Scholar]
14. Bagley S, Seidler R J, Brenner D J. Klebsiella planticola sp. nov.: a new species of Enterobacteriaceae found primarily in nonclinical environments. Curr Microbiol. 1981;6:105–109.[Google Scholar]
15. Bagley S T, Seidler R J, Talbot H W J, Morrow J E. Isolation of Klebsiellae from within living wood. Appl Environ Microbiol. 1978;36:178–185.[PMC free article] [PubMed] [Google Scholar]
16. Balish M J, Jensen J, Uehling D T. Bladder mucin: a scanning electron microscopy study in experimental cystitis. J Urol. 1982;128:1060–1063. [PubMed] [Google Scholar]
17. Barberis L I, Eraso A J, Pájaro M C, Albesa I. Molecular weight determination and partial characterization of Klebsiella pneumoniae hemolysins. Can J Microbiol. 1986;32:884–888. [PubMed] [Google Scholar]
18. Bascomb S, Lapage S P, Willcox W R, Curtis M A. Numerical classification of the tribe Klebsiellae. J Gen Microbiol. 1971;66:279–295. [PubMed] [Google Scholar]
19. Batshon B A, Baer H, Shaffer M F. Immunologic paralysis produced in mice by Klebsiella pneumoniae type 2 polysaccharide. J Immunol. 1963;90:121–126. [PubMed] [Google Scholar]
20. Bauernfeind A. Epidemiological typing of Klebsiella by bacteriocins. Methods Microbiol. 1984;16:213–224.[Google Scholar]
21. Bauernfeind A, Petermüller C, Schneider R. Bacteriocins as tools in analysis of nosocomial Klebsiella pneumoniae infections. J Clin Microbiol. 1981;14:15–19.[PMC free article] [PubMed] [Google Scholar]
22. Bauernfeind A, Rosenthal E, Eberlein E, Holley M, Schweighart S. Spread of Klebsiella pneumoniae producing SHV-5 beta-lactamase among hospitalized patients. Infection. 1993;21:18–22. [PubMed] [Google Scholar]
23. Benjamin W H, Turnbough C L, Posey B S, Briles D E. The ability of Salmonella typhimurium to produce the siderophore enterobactin is not a virulence factor in mouse typhoid. Infect Immun. 1985;50:392–397.[PMC free article] [PubMed] [Google Scholar]
24. Bennet R, Eriksson M, Melen B, Zetterström R. Changes in the incidence and spectrum of neonatal septicemia during a fifteen-year period. Acta Paediatr Scand. 1985;74:687–690. [PubMed] [Google Scholar]
25. Bennett C J, Young M N, Darrington H. Differences in urinary tract infection in male and female spinal cord injury patients on intermittent catheterization. Paraplegia. 1995;33:69–72. [PubMed] [Google Scholar]
26. Bergogne-Berezin E. Nosocomial pathogens: new pathogens, incidence, prevention. Presse Med. 1995;24:89–97. [PubMed] [Google Scholar]
27. Bingen E H, Denamur E, Elion J. Use of ribotyping in epidemiological surveillance of nosocomial outbreaks. Clin Microbiol Rev. 1994;7:311–327.[PMC free article] [PubMed] [Google Scholar]
28. Bingen E H, Desjardins P, Arlet G, Bourgeois F, Marianikurkdjian P, Lambertzechovsky N Y, Denamur E, Philippon A, Elion J. Molecular epidemiology of plasmid spread among extended broad-spectrum beta-lactamase-producing Klebsiella pneumoniae isolates in a pediatric hospital. J Clin Microbiol. 1993;31:179–184.[PMC free article] [PubMed] [Google Scholar]
29. Björkstén B, Kaijser B. Interaction of human serum and neutrophils with Escherichia coli strains: differences between strains isolated from urine of patients with pyelonephritis or asymptomatic bacteriuria. Infect Immun. 1978;22:308–311.[PMC free article] [PubMed] [Google Scholar]
30. Bradford P A, Urban C, Mariano N, Projan S J, Rahal J J, Bush K. Imipenem resistance in Klebsiella pneumoniae is associated with the combination of ACT-1, a plasmid-mediated AmpC β-lactamase, and the loss of an outer membrane protein. Antimicrob Agents Chemother. 1997;41:563–569.[PMC free article] [PubMed] [Google Scholar]
31. Brenner D J, Farmer III J J, Hickman F W, Asbury M A, Steigerwalt A G. Taxonomic and nomenclature changes in Enterobacteriaceae. HEW publication (CDC) 79-8356. Atlanta, Ga: Centers for Disease Control; 1977. [Google Scholar]
32. Brock J H, Williams P H, Licéaga J, Wooldridge K G. Relative availability of transferrin-bound iron and cell-derived iron to aerobactin-producing and enterobactin-producing strains of Escherichia coli and to other microorganisms. Infect Immun. 1991;59:3185–3190.[PMC free article] [PubMed] [Google Scholar]
33. Brown C, Seidler R J. Potential pathogens in the environment: Klebsiella pneumoniae, a taxonomic and ecological enigma. Appl Microbiol. 1973;25:900–904.[PMC free article] [PubMed] [Google Scholar]
34. Bryan C S, Hornung C A, Reynolds K L, Brenner E R. Endemic bacteremia in Columbia, South Carolina. Am J Epidemiol. 1986;123:113–127. [PubMed] [Google Scholar]
35. Bryan C S, Reynolds K L, Brenner E R. Analysis of 1,186 episodes of gram-negative bacteremia in non-university hospitals: the effects of antimicrobial therapy. Rev Infect Dis. 1983;5:629–638. [PubMed] [Google Scholar]
36. Buffenmeyer C L, Rychek R R, Yee R B. Bacteriocin (klebocin) sensitivity typing of Klebsiella. J Clin Microbiol. 1976;4:239–244.[PMC free article] [PubMed] [Google Scholar]
37. Bullen J J, Rogers H J, Griffiths E. Role of iron in bacterial infection. Curr Top Microbiol Immunol. 1978;80:1–35. [PubMed] [Google Scholar]
38. Burwen D R, Banerjee S N, Gaynes R P. Ceftazidime resistance among selected nosocomial gram-negative bacilli in the United States. J Infect Dis. 1994;170:1622–1625. [PubMed] [Google Scholar]
39. Campbell W N, Hendrix E, Cryz S, Cross A S. Immunogenicity of a 24-valent Klebsiella capsular polysaccharide vaccine and an eight-valent Pseudomonas O-polysaccharide conjugate vaccine administered to victims of acute trauma. Clin Infect Dis. 1996;23:179–181. [PubMed] [Google Scholar]
40. Carpenter J L. Klebsiella pulmonary infections: occurrence at one medical center and review. Rev Infect Dis. 1990;12:672–682. [PubMed] [Google Scholar]
41. Casewell M, Talsania H G. Predominance of certain klebsiella capsular types in hospitals in the United Kingdom. J Infect. 1979;1:77–79.[Google Scholar]
42. Casewell M W, Phillips I. Epidemiological patterns of klebsiella colonization and infection in an intensive care ward. J Hyg Camb. 1978;80:295–300.[PMC free article] [PubMed] [Google Scholar]
43. Casewell M W, Phillips I. Hands as a route of transmission for Klebsiella species. Br Med J. 1977;2:1315–1317.[PMC free article] [PubMed] [Google Scholar]
44. Centers for Disease Control. National nosocomial infections study report. Annual Summary 1983. Atlanta, Ga: Centers for Disease Control; 1985. pp. 9SS–21SS. [Google Scholar]
45. Centers for Disease Control. National nosocomial infections study report. Annual Summary 1975. Atlanta, Ga: Centers for Disease Control; 1977. [Google Scholar]
46. Centers for Disease Control. National nosocomial infections study report. Annual Summary 1979. Atlanta, Ga: Centers for Disease Control; 1982. [Google Scholar]
47. Centers for Disease Control. Nosocomial infection surveillance, 1983. CDC Surveillance Summaries. 1984;33:955–22SS.[Google Scholar]
48. Christensen S C, Korner B. An endemic caused by multiresistant Klebsiella in an urological unit. Scand J Urol Nephrol. 1972;6:232–238. [PubMed] [Google Scholar]
49. Ciurana B, Tomás J M. Role of lipopolysaccharide and complement in susceptibility of Klebsiella pneumoniae to nonimmune serum. Infect Immun. 1987;55:2741–2746.[PMC free article] [PubMed] [Google Scholar]
50. Clegg S, Gerlach G F. Enterobacterial fimbriae. J Bacteriol. 1987;169:934–938.[PMC free article] [PubMed] [Google Scholar]
51. Combe M L, Pons J L, Sesboue R, Martin J P. Electrophoretic transfer from polyacrylamide gel to nitrocellulose sheets: a new method to characterize multilocus enzyme genotypes of Klebsiella strains. Appl Environ Microbiol. 1994;60:26–30.[PMC free article] [PubMed] [Google Scholar]
52. Cooke E M, Pool R, Brayson J C, Edmondson A S, Munro M E, Shinebaum R. Further studies on the source of Klebsiella aerogenes in hospital patients. J Hyg Camb. 1979;83:391–395.[PMC free article] [PubMed] [Google Scholar]
53. Coovadia Y M, Johnson A P, Bhana R H, Hutchinson G R, George R C, Hafferjee I E. Multiresistant Klebsiella pneumoniae in a neonatal nursery: the importance of maintenance of infection control policies and procedures in the prevention of outbreaks. J Hosp Infect. 1992;22:197–205. [PubMed] [Google Scholar]
54. Cowan S T, Steel K J, Shaw C, Duguid J P. A classification of the Klebsiella group. J Gen Microbiol. 1960;23:601–612. [PubMed] [Google Scholar]
55. Cryz S J. Progress in immunization against Klebsiella infections. Eur J Clin Microbiol. 1983;2:523–528. [PubMed] [Google Scholar]
56. Cryz S J, Fürer E, Germanier R. Experimental Klebsiella pneumoniae burn wound sepsis: role of capsular polysaccharide. Infect Immun. 1984;43:440–441.[PMC free article] [PubMed] [Google Scholar]
57. Cryz S J, Jr, Fürer E, Germanier R. Safety and immunogenicity of Klebsiella pneumoniae K1 capsular polysaccharide vaccine in humans. J Infect Dis. 1985;151:665–671. [PubMed] [Google Scholar]
58. Cryz S J, Jr, Mortimer P, Cross A S, Fürer E, Germanier R. Safety and immunogenicity of a polyvalent Klebsiella capsular polysaccharide vaccine in humans. Vaccine. 1986;4:15–20. [PubMed] [Google Scholar]
59. Cryz S J, Mortimer P M, Mansfield V, Germanier R. Seroepidemiology of Klebsiella bacteremic isolates and implications for vaccine development. J Clin Microbiol. 1986;23:687–690.[PMC free article] [PubMed] [Google Scholar]
60. Curie K, Speller D C E, Simpson R A, Stephens M, Cooke D I. A hospital epidemic caused by a gentamicin-resistant Klebsiella aerogenes. J Hyg Camb. 1978;80:115–123.[PMC free article] [PubMed] [Google Scholar]
61. Darfeuille-Michaud A, Jallat C, Aubel D, Sirot D, Rich C, Sirot J, Joly B. R-plasmid-encoded adhesive factor in Klebsiella pneumoniae strains responsible for human nosocomial infections. Infect Immun. 1992;60:44–45.[PMC free article] [PubMed] [Google Scholar]
62. Davis T J, Matsen J M. Prevalence and characteristics of Klebsiella species: relation to association with a hospital environment. J Infect Dis. 1974;130:402–405. [PubMed] [Google Scholar]
63. De Champs C, Rouby D, Guelon D, Sirot J, Sirot D, Beytout D, Gourgand J M. A case-control study of an outbreak of infections caused by Klebsiella pneumoniae strains producing CTX-1 (TEM-3) beta-lactamase. J Hosp Infect. 1991;18:5–13. [PubMed] [Google Scholar]
64. de la Torre M G, Romero-Vivas J, Martinez-Beltran J, Guerrero A, Meseguer M, Bouza E. Klebsiella bacteremia: an analysis of 100 episodes. Rev Infect Dis. 1985;7:143–150. [PubMed] [Google Scholar]
65. de Lorenzo V, Martinez J L. Aerobactin production as a virulence factor: a reevaluation. Eur J Clin Microbiol Infect Dis. 1988;7:621–629. [PubMed] [Google Scholar]
66. Di Martino P, Bertin Y, Girardeau P, Livrelli V, Joly B, Darfeuille-Michaud A. Molecular characterization and adhesive properties of CF29K, an adhesin of Klebsiella pneumoniae strains involved in nosocomial infections. Infect Immun. 1995;63:4336–4344.[PMC free article] [PubMed] [Google Scholar]
67. Di Martino P, Livrelli V, Sirot D, Joly B, Darfeuille-Michaud A. A new fimbrial antigen harbored by CAZ-5/SHV-4-producing Klebsiella pneumoniae strains involved in nosocomial infections. Infect Immun. 1996;64:2266–2273.[PMC free article] [PubMed] [Google Scholar]
68. Doebbeling B N. Epidemics: identification and management. In: Wenzel R P, editor. Prevention and control of nosocomial infections. 2nd ed. Baltimore, Md: The Williams & Wilkins Co.; 1993. pp. 177–206. [Google Scholar]
69. Domenico P, Johanson W G, Straus D C. Lobar pneumonia in rats produced by clinical isolates of Klebsiella pneumoniae. Infect Immun. 1982;37:327–335.[PMC free article] [PubMed] [Google Scholar]
70. Duggan J M, Oldfield G S, Ghosh H K. Septicaemia as a hospital hazard. J Hosp Infect. 1985;6:406–412. [PubMed] [Google Scholar]
71. Edberg S C, Piscitelli V, Cartter M. Phenotypic characteristics of coliform and noncoliform bacteria from a public water supply compared with regional and national clinical species. Appl Environ Microbiol. 1986;52:474–478.[PMC free article] [PubMed] [Google Scholar]
72. Edelman R, Taylor D N, Wasserman S S, Mcclain J B, Cross A S, Sadoff J C, Que J U, Cryz S J. Phase 1 trial of a 24-valent Klebsiella capsular polysaccharide vaccine and an eight-valent Pseudomonas O-polysaccharide conjugate vaccine administered simultaneously. Vaccine. 1994;12:1288–1294. [PubMed] [Google Scholar]
73. Edmondson A S, Cooke E M. The development and assessment of a bacteriocin typing method for Klebsiella. J Hyg Camb. 1979;82:207–233.[PMC free article] [PubMed] [Google Scholar]
74. Edmondson A S, Cooke E M, Wilcock A P D, Shinebaum R. A comparison of the properties of Klebsiella strains isolated from different sources. J Med Microbiol. 1980;13:541–550. [PubMed] [Google Scholar]
75. Edwards P R, Ewing W H. Identification of Enterobacteriaceae. 4th ed. Minneapolis, Minn: Burgess Publishing Co.; 1986. [Google Scholar]
76. Ehrenwort L, Baer H. The pathogenicity of Klebsiella pneumoniae for mice: the relationship to the quantity and rate of production of type-specific capsular polysaccharide. J Bacteriol. 1956;72:713–717.[PMC free article] [PubMed] [Google Scholar]
77. Fader R C, Davis C P. Effect of piliation on Klebsiella pneumoniae infection in rat bladders. Infect Immun. 1980;30
A Microbial Biorealm page on the genus Klebsiella
Higher order taxa:
Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacteriales; Enterobacteriaceae
Klebsiella aerogenes; K. granulomatis; K. milletis; K. oxytoca; K. cf. planticola B43; K. pneumoniae; K. senegalensis; K. singaporensis; K. variicola; K. sp.
Description and Significance
Klebsiella pneumoniae is one of the most common Gram-negative bacteria seen by physicians worldwide. Pneumonias that are caused by Klebsiella pneumoniae are difficult to control; mortality rates have even been reported as up to 50% after antibiotic treatment (Straus 1986). Nitrogen metabolism in Klebsiella aerogenes has also been studied throroughly (Senior 1975).
The Genome Sequencing Center at Washington U, St. Louis is presently sequencing Klebsiella pneumoniae MGH 78578. In addition, studies have been done to compare what is known of the Salmonella enterica serovars Typhimurium, Typhi, and Paratyphi A and Klebsiella pneumoniae genomes to the Escherichia coli K-12 genome. 1165 of the 4405 genes located in the E. coli genome are missing from all of the Salmonella genomes and K. pneumoniae genome. The K. pneumoniae genome was also slightly more divergent from the E. coli genome than the three Salmonella genomes (McClelland et al. 2000).
Cell Structure and Metabolism
Klebsiella are non-motile, rod-shaped, proteobacteria that possess a prominent polysaccharide capsule. They are facultative aerobes, capable of both fermentation and aerobic respiration. Some of these bacteria produce an extracellular toxic complex that has been shown to be "lethal for and produce extensive lung pathology in mice" (Straus 1986). It is composed of 63% capsular polysaccharide, 30% lipopolysaccharide, and 7% protein; when introduced to experimental animals in sublethal doses, the animals built up immunization due to antibody production (Straus 1986).
Klebsiella are ubiquitous and may colonize the skin, pharynx, or gastrointestinal tract in humans. They form large moist colonies due to "large mucoid polysaccharide capsule (K antigen) that protects from phagocytosis and aids in adherence" (U of Maryland).
Klebsiella pneumoniae and Klebsiella oxytoca are both opportunistic pathogens found in the environment and in mammalian mucosal surfaces; they are commonly passed by hands of hospital personel. Common sites for nosocomial Klebsiella infections inlcude the urinary tract, lower respiratory tract, biliary tract, and surgical wound sites. Clinical syndromes caused by this bacteria inlcude pneumonia, bacteremia, thrombophlebitis, urinary tract infection, cholecystitis, diarrhea, upper respiratory tract infection, wound infection, osteomyelitis, and meningitis. Infection in the lungs, called pneumonia, leads to necrosis, inflammation, and hemorrhage in the lung tissue, which produces a thick, bloody, mucoid sputum called currant jelly sputum. People at high risk to get this are middle-aged to older men with alcoholism, diabetes, or chronic bronchopulmonary disease. Two rarer infections caused by Klebsiella bacteria are rhinoscleroma, a "chronic inflammatory process involving the nasopharynx," and ozena, a "chronic atrophic rhinitis characterized by necrosis of nasal mucosa and mucopurulent nasal discharge" (Emedicine).
K. aerogenes, like other microorganisms, uses L-glutanime as the key metabolite in nitrogen metabolism. The amide nitrogen of glutamine is important in the biosynthesis of asparagine, glucosamine 6-phosphate, tryptophan, histidine, carbamyl phosphate, p-aminobenzoate, adenosine, 5'-monophosphate, cytosine 5'-triphosphate, guanosine 5'-monophosphate, glutamate, and other amino acids. The alpha-amino group of glutamine is also transferred to an alpha-keto acid in transamination reactions. All these reactions allow the biosynthesis for the assimilation of NH3 into all amino acids (Senior 1975).
In an evironment with a high concentration of ammonia and/or organic nitrogen, however, this nitrogen fixation would not be needed. In K. aerogenes, a low concentration of ammonia and/or organic nitrogen causes the repression of the glutamate dehydrogenase and the induction of glutamate synthase, an alternative supplier of glutamate within the cell; this differs from E. coli in which glutamate dehydrogenase is progressively induced during nitrogen limitation.
- Umeh, Obiamiwe. 2002. "Klebsiella Infections." Emedicine.
- University of Maryland: KlebsiellaSummary
- Straus, David C. 1987. "Production of an extracellular toxic complex by various strains of Klebsiella pneumoniae." Infection ad Immunity, vol. 55, no. 1. American Society for Microbiology. (44-48)
- McClelland, Michael, Liliana Florea, Ken Sanderson, Sandra W. Clifton, Julian Parkhill, Carol Churcher, Gordon Dougan, Richard K. Wilson and Webb Miller. 2000. "Comparison of the Escherichia coli K-12 genome with sampled genomes of a Klebsiella pneumoniae and three Salmonella enterica serovars, Typhimurium, Typhi and Paratyphi." Nucleic Acids Research, vol. 28, no. 24. Oxford University Press. (4974-4986)
- Senior, Peter J. 1975. "Regulation of nitrogen metabolism in Escherichia coli and Klebsiella aerogenes: Studies with the continuous-culture technique." Journal of Bacteriology, vol. 123, no. 2. American Society for Microbiology. (407-418)
The Genus Klebsiella
The Prokaryotes pp 159-196 | Cite as
- Sylvain Brisse
- Francine Grimont
- Patrick A. D. Grimont
Taxonomic History and Structure
The genus Klebsiella, in the family Enterobacteriaceae, was named by Trevisan (1885) to honor the German microbiologist Edwin Klebs (1834–1913). The type species is Klebsiella pneumoniae (Schroeter, 1886; Trevisan, 1887). The first Klebsiella species ever described was a capsulated bacillus from patients with rhinoscleroma (Von Frisch, 1882). The organism was named “Klebsiella rhinoscleromatis” by Trevisan (1887).
Abel (1893) observed a capsulated bacillus, “Bacillus mucosus ozaenae” from the nasal secretion of patients with ozaena. The bacterium was later transferred to the genus Klebsiella as K. ozaenae (Bergey et al., 1925).
Friedländer (1982) described a bacterium from the lungs of a patient who had died of pneumonia. The organism was named “Hyalococcus pneumoniae “ (Schroeter, 1889) and Klebsiella pneumoniae (Trevisan, 1887). Considerable confusion occurred for many years since the organism could not be objectively separated...
KeywordsPlanticola Klebsiella Strains Podschun Brisse Terrigena
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.
Abel, R. 1893 Bakteriologische studien über Ozaena simplex Zbl. Bakteriol. Abt. I 13 161–173Google Scholar
Abraham, S. N., D. Sun, J. B. Dale, and E. H. Beachey. 1988 Conservation of the D-mannose-adhesion protein among type 1 fimbriated members of the family Enterobacteriaceae Nature 336 682–684PubMedGoogle Scholar
Adegbola, R. A., and D. C. Old. 1985 Fimbrial and non-fimbrial haemagglutinins in Enterobacter aerogenes J. Med. Microbiol. 19 35–43PubMedGoogle Scholar
Ahmad, M., C. Urban, N. Mariano, P. A. Bradford, E. Calcagni, S. J. Projan, K. Bush, and J. J. Rahal. 1999 Clinical characteristics and molecular epidemiology associated with imipenem-resistant Klebsiella pneumoniae Clin. Infect. Dis. 29(2) 352–355PubMedGoogle Scholar
Alberti, S., S. Hernandez-Alles, J. Gil, J. Reina, J. Martinez-Beltran, S. Camprubi, J. M. Tomas, and V. J. Benedi. 1993 Development of an enzyme-linked immunosorbent assay method for typing and quantitation of Klebsiella pneumoniae lipopolysaccharide: Application to serotype O1 J. Clin. Microbiol. 31(5) 1379–1381PubMedPubMedCentralGoogle Scholar
Albesa, I., A. J. Eraso, C. I. Frigerio, and A. M. Lubetkin. 1980 Hospital outbreak in a care unit for infants, due to Klebsiella tribe Revista Argentina de Microbiologia 12 39–43PubMedGoogle Scholar
Albesa, I., L. I. Barberis, M. C. Pajaro, M. C. Farnochi, and A. J. Eraso. 1985 A thiol-activated hemolysin in Gram-negative bacteria Can. J. Microbiol. 31 297–300PubMedGoogle Scholar
Allen, P., C. A. Hart, and J. R. Saunders. 1987 Isolation from Klebsiella and characterization of two rcs genes that activate colanic acid capsular biosynthesis in Escherichia coli J. Gen. Microbiol. 133 331–340PubMedGoogle Scholar
Allen, B. L., G. F. Gerlach, and S. Clegg. 1991 Nucleotide sequence and functions of mrk determinants necessary for expression of type 3 fimbriae in Klebsiella pneumoniae J. Bacteriol. 173(2) 916–920PubMedPubMedCentralGoogle Scholar
Aragão, H. D., and G. Vianna. 1913 Pesquizas sobre o granuloma venereo Mem. Inst. Oswaldo Cruz 5 211–238Google Scholar
Arakawa, Y., M. Ohta, N. Kido, Y. Fujii, T. Komatsu, and N. Kato. 1986 Close evolutionary relationship between the chromosomally encoded beta-lactamase gene of Klebsiella pneumoniae and the TEM beta-lactamase gene mediated by R plasmids FEBS Lett. 207(1) 69–74PubMedGoogle Scholar
Arakawa, Y., M. Ohta, N. Kido, M. Mori, H. Ito, T. Komatsu, Y. Fujii, and N. Kato. 1989 Chromosomal beta-lactamase of Klebsiella oxytoca, a new class A enzyme that hydrolyzes broad-spectrum beta-lactam antibiotics Antimicrob. Agents Chemother. 33(1) 63–70PubMedPubMedCentralGoogle Scholar
Arakawa, Y., M. Ohta, R. Wacharotayankun, M. Mori, N. Kido, H. Ito, T. Komatsu, T. Sugiyama, and N. Kato. 1991 Biosynthesis of Klebsiella K2 capsular polysaccharide in Escherichia coli HB101 requires the functions of rmpA and the chromosomal cps gene cluster of the virulent strain Klebsiella pneumoniae Chedid (O1:K2) Infect. Immun. 59(6) 2043–2050PubMedPubMedCentralGoogle Scholar
Arakawa, Y., R. Wacharotayankun, T. Nagatsuka, H. Ito, N. Kato, and M. Ohta. 1995 Genomic organization of the Klebsiella pneumoniae cps region responsible for serotype K2 capsular polysaccharide synthesis in the virulent strain Chedid J. Bacteriol. 177(7) 1788–1796PubMedPubMedCentralGoogle Scholar
Arlet, G., M. Rouveau, I. Casin, P. J. Bouvet, P. H. Lagrange, and A. Philippon. 1994 Molecular epidemiology of Klebsiella pneumoniae strains that produce SHV-4 beta-lactamase and which were isolated in 14 French hospitals J. Clin. Microbiol. 32(10) 2553–2558PubMedPubMedCentralGoogle Scholar
Athamna, A., I. Ofek, Y. Keisari, S. Markowitz, G. G. Dutton, and N. Sharon. 1991 Lectinophagocytosis of encapsulated Klebsiella pneumoniae mediated by surface lectins of guinea pig alveolar macrophages and human monocyte-derived macrophages Infect. Immun. 59(5) 1673–1682PubMedPubMedCentralGoogle Scholar
Ausebel, F. M. 1984 Regulation of nitrogen fixation genes Cell 37 5–6Google Scholar
Bach, S., A. de Almeida, and E. Carniel. 2000 The Yersinia high-pathogenicity island is present in different members of the family Enterobacteriaceae FEMS Microbiol. Lett. 183(2) 289–294PubMedGoogle Scholar
Baerthlein, K. 1918 Ueber bakterielle Variabilität insbesondere sogenannte Bakterienmutationem Zbl. Bakteriol. I. Abt. Orig. 81 369–435Google Scholar
Bagley, S. T., and R. J. Seidler. 1978a Primary Klebsiella identification with MacConkey-inositol-carbenicillin agar Appl. Environ. Microbiol. 36 536–538PubMedPubMedCentralGoogle Scholar
Bagley, S. T., R. J. Seidler, H. W. Talbot, and J. E. Morrow. 1978b Isolation of Klebsiella within living wood Appl. Environ. Microbiol. 36 178–185PubMedPubMedCentralGoogle Scholar
Bagley, S. T., R. J. Seidler, and D. J. Brenner. 1981 Klebsiella planticola sp. nov.: A new species of Enterobacteriaceae found primarily in non clinical environments Curr. Microbiol. 6 105–109Google Scholar
Barr, J. G. 1978 Variation in metabolism of biochemical test substrates by Klebsiella species: An epidemiological tool J. Med. Microbiol. 11 501–511PubMedGoogle Scholar
Barthélémy, M., J. Peduzii, H. B. Yaghlane, and R. Labia. 1988 Single amino acid substitution between SHV-1 b-lactamase and cefotaxime-hydrolysing SHV-2 enzyme FEBS Lett. 231 217–220PubMedGoogle Scholar
Bascomb, S., S. P. Lapage, W. R. Willcox, and M. A. Curtis. 1971 Numerical classification of the tribe Klebsielleae J. Gen. Microbiol. 66 279–295PubMedGoogle Scholar
Bastian, I., and F. J. Bowden. 1996 Amplification of Klebsiella-like sequences from biopsy samples from patients with donovanosis Clin. Infect. Dis. 23(6) 1328–1330PubMedGoogle Scholar
Bauernfeind, A., C. Petermüller, and R. Schneider. 1981 Bacteriocins as tools in analysis of nosocomial Klebsiella pneumoniae infections J. Clin. Microbiol. 14 15–19PubMedPubMedCentralGoogle Scholar
Bauernfeind, A. 1984 Epidemiological typing of Klebsiella by bacteriocins Meth. Microbiol. 16 213–224Google Scholar
Bauernfeind, A. 1996 Antibiotic susceptibility patterns of respiratory isolates of Klebsiella pneumoniae in Europe and the USA in 1992 and 1993. The Alexander Project Collaborative Group J. Antimicrob. Chemother. 38, Suppl. A 107–115PubMedGoogle Scholar
Ben-Hamouda, T., T. Foulon, A. Ben-Cheikh-Masmoudi, C. Fendri, O. Belhadj, and K. Ben-Mahrez. 2003 Molecular epidemiology of an outbreak of multiresistant Klebsiella pneumoniae in a Tunisian neonatal ward J. Med. Microbiol. 52(5) 427–433PubMedGoogle Scholar
Berger, S. A., A. A. Pollock, and A. S. Richmond. 1977 Isolation of Klebsiella ozaenae and Klebsiella rhinoscleromatis in a general hospital Am. J. Clin. Pathol. 67 499–502PubMedGoogle Scholar
Bergey, D. H. (Ed.). 1923 Bergey’s Manual of Determinative Bacteriology Williams and Wilkins Baltimore, MDGoogle Scholar
Bergey, D. H., F. C. Harrison, R. S. Breed, B. W. Hammer, and F. M. Huntoon (Eds.). 1925 Bergey’s Manual of Determinative Bacteriology Williams and Wilkins Baltimore, MD 1Google Scholar
Beynon, J., M. Cannon, V. Buchanan-Wollaston, and F. Cannon. 1983 The nif promoters of Klebsiella pneumoniae have a characteristic primary structure Cell 34 665–671PubMedGoogle Scholar
Biebl, H., A. P. Zeng, K. Menzel, and W. D. Deckwer. 1998 Fermentation of glycerol to 1,3-propanediol and 2,3-butanediol by Klebsiella pneumoniae Appl. Microbiol. Biotechnol. 50(1) 24–29PubMedGoogle Scholar
Biebl, H., K. Menzel, A. P. Zeng, and W. D. Deckwer. 1999 Microbial production of 1,3-propanediol Appl. Microbiol. Biotechnol. 52(3) 289–297PubMedGoogle Scholar
Bingen, E. H., P. Desjardins, G. Arlet, F. Bourgeois, P. Mariani-Kurkdjian, N. Y. Lambert-Zechovsky, E. Denamur, A. Philippon, and J. Elion. 1993 Molecular epidemiology of plasmid spread among extended broad-spectrum beta-lactamase-producing Klebsiella pneumoniae isolates in a pediatric hospital J. Clin. Microbiol. 31(2) 179–184PubMedPubMedCentralGoogle Scholar
Bingen, E. H., E. Denamur, and J. Elion. 1994 Use of ribotyping in epidemiological surveillance of nosocomial outbreaks Clin. Microbiol. Rev. 7(3) 311–327PubMedPubMedCentralGoogle Scholar
Blanchette, E. A., and S. J. Rubin. 1980 Seroepidemiology of clinical isolates of Klebsiella in Connecticut J. Clin. Microbiol. 11(5) 474–478PubMedPubMedCentralGoogle Scholar
Blomqvist, K., M. Nikkola, P. Lehtovaara, M. L. Suihko, U. Airaksinen, K. B. Straby, J. K. Knowles, and M. E. Penttila. 1993 Characterization of the genes of the 2,3-butanediol operons from Klebsiella terrigena and Enterobacter aerogenes J. Bacteriol. 175(5) 1392–1404PubMedPubMedCentralGoogle Scholar
Bouvet, O. M. M., P. Lenormand, and P. A. D. Grimont. 1989 Taxonomy diversity of the D-glucose oxidation pathway in the Enterobacteriaceae Int. J. System. Bacteriol. 39 63–67Google Scholar
Bouza, E., and E. Cercenado. 2002 Klebsiella and Enterobacter: Antibiotic resistance and treatment implications Semin. Respir. Infect. 17(3) 215–230PubMedGoogle Scholar
Boye, K., and D. S. Hansen. 2003 Sequencing of 16S rDNA of Klebsiella: Taxonomic relations within the genus and to other Enterobacteriaceae Int J. Med. Microbiol. 292(7–8) 495–503PubMedGoogle Scholar
Brade, L., R. Podschun, and H. Brade. 2001 A monoclonal antibody with specificity for the genus Klebsiella binds to a common epitope located in the core region of Klebsiella lipopolysaccharide J. Endotoxin Res. 7(2) 119–124PubMedGoogle Scholar
Bradford, P. A., C. Urban, N. Mariano, S. J. Projan, J. J. Rahal, and K. Bush. 1997 Imipenem resistance in Klebsiella pneumoniae is associated with the combination of ACT-1, a plasmid-mediated AmpC beta-lactamase, and the foss of an outer membrane protein Antimicrob. Agents Chemother. 41(3) 563–569PubMedPubMedCentralGoogle Scholar
Bradford, P. A. 2001 Extended-spectrum beta-lactamases in the 21st century: Characterization, epidemiology, and detection of this important resistance threat Clin. Microbiol. Rev. 14(4) 933–951PubMedPubMedCentralGoogle Scholar
Braman, S. K., R. J. Eberhart, M. A. Ashbury, and G. J. Herman. 1973 Capsular types of K. pneumoniae associated with bovine mastitis J. Am. Vet. Med. Assoc. 162 109–111PubMedGoogle Scholar
Brenner, D. J., A. G. Steigerwalt, and G. R. Fanning. 1972 Differentiation of Enterobacter aerogenes from Klebsiellae by deoxyribonucleic acid reassociation Int. J. System. Bacteriol. 22 193–200Google Scholar
Brenner, D. J., J. J. Farmer 3rd, F. W. Hickman, M. A. Asbury, and A. G. Steigerwalt. 1977 Taxonomic and Nomenclatural Changes in Enterobacteriaceae Atlanta, GAGoogle Scholar
Brewer, R. J., R. B. Galland, and H. C. Polk. 1982 Amelioration by muramyl dipeptide of the effect of induced hyperferremia upon Klebsiella infection in mice Infect. Immun. 38 175–178PubMedPubMedCentralGoogle Scholar
Brisse, S., D. Milatovic, A. C. Fluit, J. Verhoef, N. Martin, S. Scheuring, K. Kohrer, and F. J. Schmitz. 1999 Comparative in vitro activities of ciprofloxacin, clinafloxacin, gatifloxacin, levofloxacin, moxifloxacin, and trovafloxacin against Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, and Enterobacter aerogenes clinical isolates with alterations in GyrA and ParC proteins Antimicrob. Agents Chemother. 43(8) 2051–2055PubMedPubMedCentralGoogle Scholar
Brisse, S., D. Milatovic, A. C. Fluit, J. Verhoef, and F. J. Schmitz. 2000 Epidemiology of quinolone resistance of Klebsiella pneumoniae and Klebsiella oxytoca in Europe Eur J. Clin. Microbiol. Infect. Dis. 19(1) 64–68PubMedGoogle Scholar
Brisse, S., and J. Verhoef. 2001 Phylogenetic diversity of Klebsiella pneumoniae and Klebsiella oxytoca clinical isolates revealed by randomly amplified polymorphic DNA, gyrA and parC genes sequencing and automated ribotyping Int. J. Syst. Evol. Microbiol. 51(3) 915–924PubMedGoogle Scholar
Brisse, S., V. Fussing, B. Ridwan, J. Verhoef, and R. J. Willems. 2002 Automated ribotyping of vancomycin-resistant Enterococcus faecium isolates J. Clin. Microbiol. 40(6) 1977–1984PubMedPubMedCentralGoogle Scholar
Brisse, S. 2003 Automated ribotyping of bacterial strains: A standardized technology suitable for use in the construction of on-line databases and Internet exchange In: A. van Belkum, B. Duim, and J. P. Hays (Eds.) Experimental Approaches for Assessing Genetic Diversity Among Microbial Pathogens Dutch Working Party on Epidemiological Typing Wageningen, The Netherlands 23–32Google Scholar
Brisse, S., S. Issenhuth-Jeanjean, and P. A. Grimont. 2004a Molecular serotyping of Klebsiella species isolates by restriction of the amplified capsular antigen gene cluster J. Clin. Microbiol. 42(8) 3388–3398PubMedPubMedCentralGoogle Scholar
Brisse, S., T. van Himbergen, K. Kusters, and J. Verhoef. 2004b Development of a rapid identification method for Klebsiella pneumoniae phylogenetic groups and analysis of 420 clinical isolates Clin. Microbiol. Infect. 10(10) 942–945PubMedGoogle Scholar
Brown, C., and R. J. Seidler. 1973 Potential pathogens in the environment: Klebsiella pneumoniae, a taxonomic and ecological enigma Appl. Microbiol. 25 900–904PubMedPubMedCentralGoogle Scholar
Bruce, S. K., D. G. Schick, L. Tanaka, E. M. Jimenez, and J. Z. Montgomerie. 1981 Selective medium for isolation of Klebsiella pneumoniae J. Clin. Microbiol. 13 1114–1116PubMedPubMedCentralGoogle Scholar
Buffenmeyer, C. L., R. R. Rycheck, and R. B. Yee. 1976 Bacteriocin (klebocin) sensitivity typing of Klebsiella J. Clin. Microbiol. 4 239–244Google Scholar
Buré, A., P. Legrand, G. Arlet, V. Jarlier, G. Paul, and A. Philippon. 1988 Dissemination in five French hospitals of Klebsiella pneumoniae serotype K25 harbouring a new transferable enzymatic resistance to third generation cephalosporins and aztreonam Eur. J. Clin. Microbiol. 7 780–782Google Scholar
Calin, A. 1984 Spondyloarthropathies: An overview In: A. Calin (Ed.) Spondyoarthopathies Grune and Stratton Orlando, FL 1–8Google Scholar
Campbell, L. M., and I. L. Roth. 1975 Methyl violet: A selective agent for differentiation of Klebsiella pneumoniae from Enterobacter aerogenes and other Gram-negative organisms Appl. Microbiol. 30 258–261PubMedPubMedCentralGoogle Scholar
Campbell, L. M., I. L. Roth, and R. D. Klein. 1976 Evaluation of double violet agar in the isolation of Klebsiella pneumoniae from river water Appl. Environ. Microbiol. 31 212–215Google Scholar
Campbell, W. N., E. Hendrix, S. Cryz Jr., and A. S. Cross. 1996 Immunogenicity of a 24-valent Klebsiella capsular polysaccharide vaccine and an eight-valent Pseudomonas O-polysaccharide conjugate vaccine administered to victims of acute trauma Clin. Infect. Dis. 23(1) 179–181PubMedGoogle Scholar
Camprubi, S., J. Tomas, F. Munoa, C. Madrid, and A. Juarez. 1990 Influence of lipopolysaccharide on external hemolytic activity of Salmonella typhimurium and Klebsiella pneumoniae Curr. Microbiol. 20 1–3Google Scholar
Caplenas, N. R., M. S. Kanarek, and A. P. Dufour. 1981 Source and extent of Klebsiella pneumoniae in the paper industry Appl. Environ. Microbiol. 42 779–785PubMedPubMedCentralGoogle Scholar
Carpenter, J. L. 1990 Klebsiella pulmonary infections: Occurrence at one medical center and review Rev. Infect. Dis. 12(4) 672–682PubMedGoogle Scholar
Carter, J., S. Hutton, K. S. Sriprakash, D. J. Kemp, G. Lum, J. Savage, and F. J. Bowden. 1997 Culture of the causative organism of donovanosis (Calymmatobacterium granulomatis) in HEp-2 cells J. Clin. Microbiol. 35(11) 2915–2917PubMedPubMedCentralGoogle Scholar
Carter, J. S., F. J. Bowden, I. Bastian, G. M. Myers, K. S. Sriprakash, and D. J. Kemp. 1999 Phylogenetic evidence for reclassification of Calymmatobacterium granulomatis as Klebsiella granulomatis comb. nov Int. J. Syst. Bacteriol. 49 1695–700PubMedGoogle Scholar
Casewell, M. W., and H. G. Talsania. 1979 Predominance of certain Klebsiella capsular types in hospitals in the United Kingdom J. Infect. 1 77–79Google Scholar
Chand, M. S., and C. J. MacArthur. 1997 Primary atrophic rhinitis: A summary of four cases and review of the litterature Otolaryngol. Head Neck Surg. 116 554–558PubMedGoogle Scholar
Chang, F. Y., and M. Y. Chou. 1995 Comparison of pyogenic liver abscesses caused by Klebsiella pneumoniae and non-K. pneumoniae pathogens J. Formosa Med. Assoc. 94(5) 232–237Google Scholar
Chang, S. C., C. T. Fang, P. R. Hsueh, Y. C. Chen, and K. T. Luh. 2000 Klebsiella pneumoniae isolates causing liver abscess in Taiwan Diagn. Microbiol. Infect. Dis. 37(4) 279–284PubMedGoogle Scholar
Chaves, J., M. G. Ladona, C. Segura, A. Coira, R. Reig, and C. Ampurdanes. 2001 SHV-1 beta-lactamase is mainly a chromosomally encoded species-specific enzyme in Klebsiella pneumoniae Antimicrob. Agents Chemother. 45(10) 2856–2861PubMedPubMedCentralGoogle Scholar
Chelius, M. K., and E. W. Triplett. 2000 Immunolocalization of dinitrogenase reductase produced by Klebsiella pneumoniae in association with Zea mays L Appl. Environ. Microbiol. 66(2) 783–787PubMedPubMedCentralGoogle Scholar
Cheng, H. P., F. Y. Chang, C. P. Fung, and L. K. Siu. 2002 Klebsiella pneumoniae liver abscess in Taiwan is not caused by a clonal spread strain J. Microbiol. Immunol. Infect. 35(2) 85–88PubMedGoogle Scholar
Chhibber, S., and J. Bajaj. 1995 Polysaccharide-iron-regulated cell surface protein conjugate vaccine: Its role in protection against Klebsiella pneumoniae-induced lobar pneumonia Vaccine 13(2) 179–184PubMedGoogle Scholar
Ciurana, B., and J. M. Tomas. 1987 Role of lipopolysaccharide and complement in susceptibility of Klebsiella pneumoniae to nonimmune serum Infect. Immun. 55(11) 2741–2746PubMedPubMedCentralGoogle Scholar
Clegg, S., and G. F. Gerlach. 1987 Enterobacterial fimbriae J. Bacteriol. 169(3) 934–938PubMedPubMedCentralGoogle Scholar
Combe, M., J. Lemeland, M. Pestel-Caron, and J. Pons. 2000 Multilocus enzyme analysis in aerobic and anaerobic bacteria using gel electrophoresis-nitrocellulose blotting FEMS Microbiol. Lett. 185(2) 169–174PubMedGoogle Scholar
Cooke, E. M., J. C. Brayson, A. S. Edmondson, and D. Hall. 1979 An investigation into the incidence and sources of klebsiella infections in hospital patients J. Hyg. (Lond.) 82 473–480Google Scholar
Coque, T. M., A. Oliver, J. C. Perez-Diaz, F. Baquero, and R. Canton. 2002 Genes encoding TEM-4, SHV-2, and CTX-M-10 extended-spectrum beta-lactamases are carried by multiple Klebsiella pneumoniae clones in a single hospital (Madrid, 1989 to 2000) Antimicrob. Agents Chemother. 46(2) 500–510PubMedPubMedCentralGoogle Scholar
Cortes, G., N. Borrell, B. de Astorza, C. Gomez, J. Sauleda, and S. Alberti. 2002a Molecular analysis of the contribution of the capsular polysaccharide and the lipopolysaccharide O side chain to the virulence of Klebsiella pneumoniae in a murine model of pneumonia Infect. Immun. 70(5) 2583–2590PubMedPubMedCentralGoogle Scholar
Cortes, G., B. de Astorza, V. J. Benedi, and S. Alberti. 2002b Role of the htrA gene in Klebsiella pneumoniae virulence Infect. Immun. 70(9) 4772–4776PubMedPubMedCentralGoogle Scholar
Cotton, M. F., E. Wasserman, C. H. Pieper, D. C. Theron, D. van Tubbergh, G. Campbell, F. C. Fang, and J. Barnes. 2000 Invasive disease due to extended spectrum beta-lactamase-producing Klebsiella pneumoniae in a neonatal unit: The possible role of cockroaches J. Hosp. Infect. 44(1) 13–17PubMedGoogle Scholar
Cowan, S. T. S., K. J., and C. Shaw. 1960 A classification of the Klebsiella group J. Gen. Microbiol. 23 601–612PubMedGoogle Scholar
Cryz Jr., S. J., E. Fürer, and R. Germanier. 1984a Experimental Klebsiella pneumoniae burn wound sepsis: Role of capsular polysaccharide Infect. Immun. 37 327–335Google Scholar
Cryz Jr., S. J., E. Fürer, and R. Germanier. 1984b Prevention of fatal experimental burn-wound sepsis due to Klebsiella pneumoniae KP1-0 by immunization with homologous capsular polysaccharide J. Infect. Dis. 150 817–822PubMedGoogle Scholar
Cryz, S. J., E. Fürer, and R. Germanier. 1985 Purification and vaccine potential of Klebsiella capsular polysaccharides Infect. Immun. 50 225–230PubMedPubMedCentralGoogle Scholar
Cryz Jr., S. J., P. M. Mortimer, V. Mansfield, and R. Germanier. 1986 Seroepidemiology of Klebsiella pneumoniae bacteremic isolates and implications for vaccine development J. Clin. Microbiol. 23 687–690PubMedPubMedCentralGoogle Scholar
Cryz Jr., S. J., T. L. Pitt, B. Ayling-Smith, and J. U. Que. 1990 Immunological cross-reactivity between Enterobacter aerogenes and Klebsiella capsular polysaccharides Microb. Pathogen. 9 127–1Google Scholar
Darfeuille-Michaud, A., C. Jallat, D. Aubel, D. Sirot, C. Rich, J. Sirot, and B. Joly. 1992 R-plasmid-encoded adhesive factor in Klebsiella pneumoniae strains responsible for human nosocomial infections Infect. Immun. 60(1) 44–55PubMedPubMedCentralGoogle Scholar
Davis, T. J., and J. M. Matsen. 1974 Prevalence and characteristics of Klebsiella species: Relation to association with a hospital environment J. Infect. Dis. 130 402–405PubMedGoogle Scholar
Deguchi, T., A. Fukuoka, M. Yasuda, M. Nakano, S. Ozeki, E. Kanematsu, Y. Nishino, S. Ishihara, Y. Ban, and Y. Kawada. 1997 Alterations in the GyrA subunit of DNA gyrase and the ParC subunit of topoisomerase IV in quinolone-resistant clinical isolates of Klebsiella pneumoniae Antimicrob. Agents Chemother. 41(3) 699–701PubMedPubMedCentralGoogle Scholar
de la Torre, M. G., J. Romero-Vivas, and J. Martinez-Beltràn. 1985 Klebsiella bacteremia: An analysis of 100 episodes Rev. Infect. Dis. 7 143–150Google Scholar
Deschamps, A. M., P. Henno, C. Pernelle, L. Caignault, and J. M. Lebeault. 1979 Bench scale reactors for composting research Biotechnol. Lett. 1 239–244Google Scholar
Deschamps, A. M., and J. M. Lebeault. 1980a Recherche de bactéries cellulolytiques par la méthode à la cellulose-azure Ann. Microbiol. (Inst. Pasteur) 131A 77–81Google Scholar
Deschamps, A. M., G. Mahoudeau, M. Conti, and J. M. Lebeault. 1980b Bacteria degrading tannic acid and related compounds J. Ferment. Technol. 58 93–97Google Scholar
Deschamps, A. M., G. Mahoudeau, and J. M. Lebeault. 1980c Fast degradation of kraft-lignin by bacteria Eur. J. Appl. Microbiol. Biotechnol. 9 45–51Google Scholar
Deschamps, A. M., and J. M. Lebeault. 1981 Bacterial degradation of nutrition of tannins In: M. Moo-Young and C. W. Robinson (Eds.) Advances in Biotechnology Pergamon Press New York, NY 2 639–644Google Scholar
Deschamps, A. M., C. Richard, and J. M. Lebeault. 1983 Bacteriology and nutrition of environmental strains of Klebsiella pneumoniae involved in wood and bark decay Ann. Microbiol. (Inst. Pasteur) 134A 189–196Google Scholar
Dillon, R. J., C. T. Vennard, and A. K. Charnley. 2002 A note: Gut bacteria produce components of a locust cohesion pheromone J. Appl. Microbiol. 92(4) 759–763PubMedGoogle Scholar
Di Martino, P., V. Livrelli, D. Sirot, B. Joly, and A. Darfeuille-Michaud. 1996 A new fimbrial antigen harbored by CAZ-5/SHV-4-producing Klebsiella pneumoniae strains involved in nosocomial infections Infect. Immun. 64(6) 2266–2273PubMedPubMedCentralGoogle Scholar
Di Martino, P., N. Cafferini, B. Joly, and A. Darfeuille-Michaud. 2003 Klebsiella pneumoniae type 3 pili facilitate adherence and biofilm formation on abiotic surfaces Res. Microbiol. 154(1) 9–16PubMedGoogle Scholar
Domenico, P., W. G. Johanson., and D. C. Straus. 1982 Lobar pneumonia in rats produced by clinical isolates of Klebsiella pneumoniae Infect. Immun. 37 327–335PubMedPubMedCentralGoogle Scholar
Dong, Y., J. D. Glasner, F. R. Blattner, and E. W. Triplett. 2001 Genomic interspecies microarray hybridization: Rapid discovery of three thousand genes in the maize endophyte, Klebsiella pneumoniae 342, by microarray hybridization with Escherichia coli K-12 open reading frames Appl. Environ. Microbiol. 67(4) 1911–1921PubMedPubMedCentralGoogle Scholar
Dong, Y., M. K. Chelius, S. Brisse, N. Kozyrovska, G. Kovtunovych, R. Podschun, and E. W. Triplett. 2003 Comparisons between two Klebsiella: The plant endophyte K. pneumoniae 342 and a clinical isolate, K. pneumoniae MGH78578 Symbiosis 35 247–259Google Scholar
Donta, S. T., P. Peduzzi, A. S. Cross, J. Sadoff, C. Haakenson, S. J. Cryz Jr., C. Kauffman, S. Bradley, G. Gafford, D. Elliston, T. R. Beam Jr., J. F. John Jr., B. Ribner, R. Cantey, C. H. Welsh, R. T. Ellison 3rd, E. J. Young, R. J. Hamill, H. Leaf, R. M. Schein, M. Mulligan, C. Johnson, E. Abrutyn, J. M. Griffiss, D. Slagle, et al. 1996 Immunoprophylaxis against Klebsiella and Pseudomonas aeruginosa infections: The Federal Hyperimmune Immunoglobulin Trial Study Group J. Infect. Dis. 174(3) 537–543PubMedGoogle Scholar
Drancourt, M., C. Bollet, A. Carta, and P. Rousselier. 2001 Phylogenetic analyses of Klebsiella species delineate Klebsiella and Raoultella gen. nov., with description of Raoultella ornithinolytica comb. nov., Raoultella terrigena comb. nov. and Raoultella planticola comb. nov Int. J. Syst. Evol. Microbiol. 51(3) 925–932PubMedGoogle Scholar
Dufour, A. P., and V. J. Cabelli. 1976 Characteristics of Klebsiella from textile finishing plant effluents J. Water Pollut. Control Fed. 48 872–879PubMedGoogle Scholar
Duguid, J. P. 1959 Fimbriae and adhesive properties in Klebsiella strains J. Gen. Microbiol. 21 271–286PubMedGoogle Scholar
Duncan, D. W., and W. E. Razzell. 1972 Klebsiella biotypes among coliforms isolated from forest environments and farm produce Appl. Microbiol. 24 933–938PubMedPubMedCentralGoogle Scholar
Dutka, B. J., K. Jones, and H. Bailey. 1987 Enumeration of Klebsiella spp. in cold water by using MacConkey inositol-potassium tellurite Appl. Environ. Microbiol. 53 1716–1717PubMedPubMedCentralGoogle Scholar
Ebringer, R. W., D. R. Cawdell, P. Cowling, and A. Ebringer. 1979 Sequential studies in ankylosing spondylitis: Association of Klebsiella pneumoniae and active disease Ann. Rheum. Dis. 37 146–151Google Scholar
Edelman, R., D. N. Taylor, S. S. Wasserman, J. B. McClain, A. S. Cross, J. C. Sadoff, J. U. Que, and S. J. Cryz. 1994 Phase 1 trial of a 24-valent Klebsiella capsular polysaccharide vaccine and an eight-valent Pseudomonas O-polysaccharide conjugate vaccine administered simultaneously Vaccine 12(14) 1288–1294PubMedGoogle Scholar
Edmonston, A. S., and E. M. Cooke. 1979a The development and assessment of a bacteriocin typing method for Klebsiella J. Hyg. (Cambridge) 82 207–223Google Scholar
Edmonston, A. S., and E. M. Cooke. 1979b The production of antisera to the Klebsiella capsular antigens J. Appl. Bacteriol. 46 579–584Google Scholar
Edwards, P. R. 1928 The relation of encapsulated bacilli found in metritis in mares to encapsulated bacilli from human sources J. Bacteriol. 15 245–266PubMedPubMedCentralGoogle Scholar
Edwards, P. R., and W. H. Ewing. 1972 Identification of Enterobacteriaceae Burgess Publishing Minneapolis, MNGoogle Scholar
Eickoff, T. C., B. W. Steinhauer, and M. Finland. 1966 The Klebsiella-Enterobacter-Serratia division: Biochemical and serological characteristitcs and susceptibility to antibiotics Ann. Intern. Med. 65 1163–1179Google Scholar
Eisen, D., E. G. Russell, M. Tymms, E. J. Roper, M. L. Grayson, and J. Turnidge. 1995 Random amplified polymorphic DNA and plasmid analyses used in investigation of an outbreak of multiresistant Klebsiella pneumoniae J. Clin. Microbiol. 33(3) 713–717PubMedPubMedCentralGoogle Scholar
Escherich, T. 1885 Die darmbakterien des neugeborenen und saunglings Fortsch. Deutsch. Med. 3 515–522Google Scholar
Essa, A. M., L. E. Macaskie, and N. L. Brown. 2002 Mechanisms of mercury bioremediation Biochem. Soc. Trans. 30(4) 672–674PubMedGoogle Scholar
Ewing, W. H. (Ed.). 1986 Edwards and Ewing’s Identification of Enterobacteriaceae Elsevier New York, NYGoogle Scholar
Fader, R. C., and C. P. Davis. 1982 Klebsiella pneumoniae-induced experimental pyelitis: The effect of piliation on infectivity J. Urol. 128(1) 197–201PubMedGoogle Scholar
Fader, R. C., K. Gondesen, B. Tolley, D. G. Ritchie, and P. Moller. 1988 Evidence that in vitro adherence of Klebsiella pneumoniae to ciliated hamster tracheal cells is mediated by type 1 fimbriae Infect. Immun. 56 3011–3013PubMedPubMedCentralGoogle Scholar
Farmer, J. J. I., M. A. Asbury, F. W. Hickman-Brenner, D. J. Brenner, and the Enterobacteriaceae Study Group. 1980 Enterobacter sakazaki: A new species of Enterobacteriaceae isolated from clinical specimens Int. J. System. Bacteriol. 30 569–584Google Scholar
Farmer, J. J. I., B. R. Davis, F. W. Hickman-Brenner, A. McWhorter, G. P. Huntley-Carter, M. A. Asbury, C. Riddle, H. G. Wathen-Grady, C. Elias, G. R. Fanning, A. G. Steigerwalt, C. M. O’Hara, G. K. Morris, P. B. Smith, and D. J. Brenner. 1985 Biochemical identification of new species and biogroups of Enterobacteriaceae isolated from clinical specimens J. Clin. Microbiol. 21 46–76PubMedPubMedCentralGoogle Scholar
Favre-Bonte, S., A. Darfeuille-Michaud, and C. Forestier. 1995 Aggregative adherence of Klebsiella pneumoniae to human intestine-407 cells Infect. Immun. 63(4) 1318–1328PubMedPubMedCentralGoogle Scholar
Favre-Bonte, S., B. Joly, and C. Forestier. 1999a Consequences of reduction of Klebsiella pneumoniae capsule expression on interactions of this bacterium with epithelial cells Infect. Immun. 67(2) 554–561PubMedPubMedCentralGoogle Scholar
Favre-Bonte, S., T. R. Licht, C. Forestier, and K. A. Krogfelt. 1999b Klebsiella pneumoniae capsule expression is necessary for colonization of large intestines of streptomycin-treated mice Infect. Immun. 67(11) 6152–6156PubMedPubMedCentralGoogle Scholar
Feldman, C., C. Smith, H. Levy, P. Ginsburg, S. D. Miller, and H. J. Koornhof. 1990 Klebsiella pneumoniae bacteraemia at an urban general hospital J. Infect. 20 21–31PubMedGoogle Scholar
Feldman, C., S. Ross, A. G. Mahomed, J. Omar, and C. Smith. 1995 The aetiology of severe community-acquired pneumonia and its impact on initial, empiric, antimicrobial chemotherapy Respir. Med. 89(3) 187–192PubMedGoogle Scholar
Fernandez-Rodriguez, A., R. Canton, J. C. Perez-Diaz, J. Martinez-Beltran, J. J. Picazo, and F. Baquero. 1992 Aminoglycoside-modifying enzymes in clinical isolates harboring extended-spectrum beta-lactamases Antimicrob. Agents Chemother. 36(11) 2536–2538PubMedPubMedCentralGoogle Scholar
Ferragut, C., D. Izard, F. Gavini, K. Kersters, J. De Ley, and H. Leclerc. 1983 Klebsiella trevisanii: A new species from water and soil Int. J. System. Bacteriol. 33 133–142Google Scholar
Ferragut, C., K. Kersters, and J. De Ley. 1989 Protein electrophoretic and DNA homology analysis of Klebsiella strains System. Appl. Microbiol. 11 121–127Google Scholar
Fiedler, G., M. Pajatsch, and A. Bock. 1996 Genetics of a novel starch utilisation pathway present in Klebsiella oxytoca J. Molec. Biol. 256(2) 279–291PubMedGoogle Scholar
Finegold, S. M., V. L. Sutter, and G. E. Mathison. 1983 Normal indigenous intestinal flora In: D. E. Hentges (Ed.) Human Intestinal Microflora in Health and Disease Academic Press New York, NY 1 3–31Google Scholar
Flügge, C. F. C. W. 1886 Die Mikroorganismen Leipzig, GermanyGoogle Scholar
Fournier, B., C. Y. Lu, P. H. Lagrange, R. Krishnamoorthy, and A. Philippon. 1995 Point mutation in the pribnow box, the molecular basis of beta-lactamase overproduction in Klebsiella oxytoca Antimicrob. Agents Chemother. 39(6) 1365–1368PubMedPubMedCentralGoogle Scholar
Fournier, B., P. H. Roy, P. H. Lagrange, and A. Philippon. 1996 Chromosomal beta-lactamase genes of Klebsiella oxytoca are divided into two main groups, blaOXY-1 and blaOXY-2 Antimicrob. Agents Chemother. 40(2) 454–459PubMedPubMedCentralGoogle Scholar
Fox, J. G., and M. W. Rohovsky. 1975 Meningitis caused by Klebsiella spp. in two Rhesus monkeys J. Am. Vet. Med. Assoc. 67 634–636Google Scholar
French, G. L., K. P. Shannon, and N. Simmons. 1996 Hospital outbreak of Klebsiella pneumoniae resistant to broad-spectrum cephalosporins and beta-lactam-beta-lactamase inhibitor combinations by hyperproduction of SHV-5 beta-lactamase J. Clin. Microbiol. 34(2) 358–363PubMedPubMedCentralGoogle Scholar
Friedländer, C. 1882 Ueber die Schizomyceten bei der acuten fibrösen Pneumonie Virchows Arch. Pathol. Anat. Physiol. 87 319–324Google Scholar
Friedrich, B., and B. Magasanik. 1977 Urease of Klebsiella aerogenes: Control of its synthesis by glutamine synthetase J. Bacteriol. 131 446–452PubMedPubMedCentralGoogle Scholar
Fuentes, F. A., T. C. Hazen, A. J. Lopez-Torres, and P. Rechani. 1985 Klebsiella pneumoniae in orange juice concentrate Appl. Environ. Microbiol. 49 1527–1529PubMedPubMedCentralGoogle Scholar
Fujita, S., and F. Matsubara. 1984 Latex agglutination test for O serogrouping of Klebsiella species Microbiol. Immunol. 28(6) 731–734PubMedGoogle Scholar
Fumagalli, O., B. D. Tall, C. Schipper, and T. A. Oelschlaeger. 1997 N-glycosylated proteins are involved in efficient internalization of Klebsiella pneumoniae by cultured human epithelial cells Infect. Immun. 65(11) 4445–4451PubMedPubMedCentralGoogle Scholar
Fung, C. P., B. S. Hu, F. Y. Chang, S. C. Lee, B. I. Kuo, M. Ho, L. K. Siu, and C. Y. Liu. 2000 A 5-year study of the seroepidemiology of Klebsiella pneumoniae: High prevalence of capsular serotype K1 in Taiwan and implication for vaccine efficacy J. Infect. Dis. 181(6) 2075–2079PubMedGoogle Scholar
Fung, C. P., F. Y. Chang, S. C. Lee, B. S. Hu, B. I. Kuo, C. Y. Liu, M. Ho, and L. K. Siu. 2002 A global emerging disease of Klebsiella pneumoniae liver abscess: Is serotype K1 an important factor for complicated endophthalmitis? Gut 50(3) 420–424PubMedPubMedCentralGoogle Scholar
Gassama, A., P. S. Sow, F. Fall, P. Camara, A. Gueye-N’diaye, R. Seng, B. Samb, S. M’Boup, and A. Aidara-Kane. 2001 Ordinary and opportunistic enteropathogens associated with diarrhea in Senegalese adults in relation to human immunodeficiency virus serostatus Int. J. Infect. Dis. 5(4) 192–198PubMedPubMedCentralGoogle Scholar
Gaston, M. A., B. A. Ayling-Smith, and T. Pitt. 1987 New bacteriophage typing scheme for subdivision of the freauent capsular serotypes of Klebsiella spp J. Clin. Microbiol. 25 1228–1232PubMedPubMedCentralGoogle Scholar
Gavini, F., H. Leclerc, B. Lefebvre, C. Ferrragut, and D. Izard. 1977 Etude taxonomique d’Entérobactéries appartenant ou apparentées au genre Klebsiella Ann. Microbiol. (Inst. Pasteur) 128B 45–50Google Scholar
Gavini, F., D. Izard, P. A. D. Grimont, A. Beji, E. Ageron, and H. Leclerc. 1986 Priority of Klebsiella planticola Bagley, Seidler, and Brenner 1982 over Klebsiella trevisanii Ferragut, Izard, Gavini, Kersters, DeLey, and Leclerc 1983 Int. J. System. Bacteriol. 36 486–488Google Scholar
Gerlach, G.-F., B. Allen, and S. Clegg. 1989a Type 3 fimbriae among Enterobacteria and the ability of spermidine to inhibit MR/K hemagglutination Infect. Immun. 57 219–224PubMedPubMedCentralGoogle Scholar
Gerlach, G.-F., S. Clegg, and B. L. Allen. 1989b Identification and characterization of the gene encoding the type 3 and type 1 fimbrial adhesins of Klebsiella pneumoniae J. Bacteriol. 171 1262–1270PubMedPubMedCentralGoogle Scholar
Goetsch, L., A. Gonzalez, H. Plotnicky-Gilquin, J. F. Haeuw, J. P. Aubry, A. Beck, J. Y. Bonnefoy, and N. Corvaia. 2001 Targeting of nasal mucosa-associated antigen-presenting cells in vivo with an outer membrane protein A derived from Klebsiella pneumoniae Infect. Immun. 69(10) 6434–6444PubMedPubMedCentralGoogle Scholar
Goldstein, E. J. C., R. P. Lewis, W. J. Martin, and P. H. Edelstein. 1978 Infections caused by Klebsiella ozaenae: A changing disease spectrum J. Clin. Microbiol. 8 413–418PubMedPubMedCentralGoogle Scholar
Gordon, D. M., and F. FitzGibbon. 1999 The distribution of enteric bacteria from Australian mammals: Host and geographical effects Microbiology 145 2663–2671PubMedGoogle Scholar
Gori, A., F. Espinasse, A. Deplano, C. Nonhoff, M. H. Nicolas, and M. J. Struelens. 1996 Comparison of pulsed-field gel electrophoresis and randomly amplified DNA polymorphism analysis for typing extended-spectrum-beta-lactamase-producing Klebsiella pneumoniae J. Clin. Microbiol. 34(10) 2448–2453PubMedPubMedCentralGoogle Scholar
Gouby, A., C. Neuwirth, G. Bourg, N. Bouziges, M. J. Carles-Nurit, E. Despaux, and M. Ramuz. 1994 Epidemiological study by pulsed-field gel electrophoresis of an outbreak of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in a geriatric hospital J. Clin. Microbiol. 32(2) 301–305PubMedPubMedCentralGoogle Scholar
Genus of gram-negative bacteria
Klebsiella is a genus of Gram-negative, oxidase-negative, rod-shaped bacteria with a prominent polysaccharide-based capsule.
Klebsiella species are found everywhere in nature. This is thought to be due to distinct sublineages developing specific niche adaptations, with associated biochemical adaptations which make them better suited to a particular environment. They can be found in water, soil, plants, insects and other animals including humans.
Klebsiella is named after German-Swiss microbiologist Edwin Klebs (1834–1913). Carl Friedlander described Klebsiella bacillus which is why it was termed Friedlander bacillus for many years. The members of the genus Klebsiella are a part of the human and animal's normal flora in the nose, mouth and intestines. The species of Klebsiella are all gram-negative and usually non-motile. They tend to be shorter and thicker when compared to others in the family Enterobacteriaceae. The cells are rods in shape and generally measures 0.3 to 1.5 µm wide by 0.5 to 5.0 µm long. They can be found singly, in pairs, in chains or linked end to end. Klebsiella can grow on ordinary lab medium and do not have special growth requirements, like the other members of Enterobacteriaceae. The species are aerobic but facultatively anaerobic. Their ideal growth temperature is 35° to 37 °C, while their ideal pH level is about 7.2.
List of species
- K. aerogenes, previously known as Enterobacter aerogenes
- K. granulomatis
- K. oxytoca
- K. michiganensis
- K. pneumoniae (type-species)
- K. p. subsp. ozaenae
- K. p. subsp. pneumoniae
- K. p. subsp. rhinoscleromatis
- K. quasipneumoniae
- K. q. subsp. quasipneumoniae
- K. q. subsp. similipneumoniae
- K. grimontii
- K. variicola
Klebsiella bacteria tend to be rounder and thicker than other members of the family Enterobacteriaceae. They typically occur as straight rods with rounded or slightly pointed ends. They can be found singly, in pairs, or in short chains. Diplobacillary forms are commonly found in vivo.
They have no specific growth requirements and grow well on standard laboratory media, but grow best between 35 and 37 °C and at pH 7.2. The species are facultative anaerobes, and most strains can survive with citrate and glucose as their sole carbon sources and ammonia as their sole nitrogen source.
Members of the genus produce a prominent capsule, or slime layer, which can be used for serologic identification, but molecular serotyping may replace this method.
Members of the genus Klebsiella typically express two types of antigens on their cell surfaces. The first, O antigen, is a component of the lipopolysaccharide (LPS), of which 9 varieties exist. The second is K antigen, a capsular polysaccharide with more than 80 varieties. Both contribute to pathogenicity and form the basis for serogrouping. Based on those two major antigenic determinants several vaccines have been designed.
Klebsiella species are routinely found in the human nose, mouth, and gastrointestinal tract as normal flora; however, they can also behave as opportunistic human pathogens.Klebsiella species are known to also infect a variety of other animals, both as normal flora and opportunistic pathogens.
Klebsiella organisms can lead to a wide range of disease states, notably pneumonia, urinary tract infections, sepsis, meningitis, diarrhea, peritonitis and soft tissue infections.Klebsiella species have also been implicated in the pathogenesis of ankylosing spondylitis and other spondyloarthropathies. The majority of human Klebsiella infections are caused by K. pneumoniae, followed by K. oxytoca. Infections are more common in the very young, very old, and those with other underlying diseases, such as cancer, and most infections involve contamination of an invasive medical device.
During the last 40 years, many trials for constructing effective K. pneumoniae vaccines have been tried, and new techniques were followed to construct vaccines against Klebsiella. However, currently, no Klebsiella vaccine has been licensed for use in the US. K. pneumoniae is the most common cause of nosocomial respiratory tract and premature intensive care infections, and the second-most frequent cause of Gram-negative bacteraemia and urinary tract infections . Drug-resistant isolates remain an important hospital-acquired bacterial pathogen, add significantly to hospital stays, and are especially problematic in high-impact medical areas such as intensive care units. This antimicrobial resistance is thought to be attributable mainly to multidrug efflux pumps. The ability of K. pneumoniae to colonize the hospital environment, including carpeting, sinks, flowers, and various surfaces, as well as the skin of patients and hospital staff, has been identified as a major factor in the spread of hospital-acquired infections.
In addition to certain Klebsiella spp. being discovered as human pathogens, others such as K. variicola have been identified as emerging pathogens in humans and animals alike. For instance, K. variicola has been identified as one of the causes of bovine mastitis.
In plant systems, Klebsiella can be found in a variety of plant hosts. K. pneumoniae and K. oxytoca are able to fix atmospheric nitrogen into a form that can be used by plants, thus are called associative nitrogen fixers or diazotrophs. The bacteria attach strongly to root hairs and less strongly to the surface of the zone of elongation and the root cap mucilage. They are bacteria of interest in an agricultural context, due to their ability to increase crop yields under agricultural conditions. Their high numbers in plants are thought to be at least partly attributable to their lack of a flagellum, as flagella are known to induce plant defenses. Additionally, K. variicola is known to associate with a number of different plants including banana trees, sugarcane and has been isolated from the fungal gardens of leaf-cutter ants.
- ^Trevisan, V. "Caratteri di alcuni nuovi generi di Batteriaceae [Characteristics of some new genera of Bacteriaceae]." Atti. Accad. Fis.-Med.-Stat. Milano (Ser 4) (1885) 3:92-106.
- ^"Klebsiella". NCBI taxonomy. Bethesda, MD: National Center for Biotechnology Information. Retrieved 24 April 2019.
- ^Ryan KJ; Ray CG, eds. (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. p. 370. ISBN .
- ^ abcdBagley S (1985). "Habitat association of Klebsiella species". Infect Control. 6 (2): 52–8. doi:10.1017/S0195941700062603. PMID 3882590.
- ^ abBrisse S, Grimont F, Grimont PD (2006). Prokaryotes. New York, NY: Springer New York. pp. 159–196. ISBN .
- ^Ristucci, Patricia; Cunha, Burke (July 1984). "Klebsiella". Infection Control. 5 (7): 343–348. doi:10.1017/S0195941700060549. JSTOR 30144997. PMID 6564087.
- ^ abcdeRistuccia, Patricia A; Cunha Burke A (1984). "Klebsiella". Topics in Clinical Microbiology. 5 (7): 343–348. JSTOR 30144997.
- ^Brisse, Sylvain; S Issenhuth-Jeanjean; P AD Grimont (2004). "Molecular Serotyping of Klebsiella Species Isolates by Restriction of the Amplified Capsular Antigen Gene Cluster". Journal of Clinical Microbiology. 42 (8): 3388–3398. doi:10.1128/jcm.42.8.3388-3398.2004. PMC 497587. PMID 15297473.
- ^Podschun, R; Ullmann, U (October 1998). "Klebsiella spp. as Nosocomial Pathogens: Epidemiology, Taxonomy, Typing Methods, and Pathogenicity Factors". Clinical Microbiology Reviews. 11 (4): 589–603. PMC 88898.
- ^Ahmad, TA; El-Sayed, LH; Medhat, H; Hessen, A; El-Ashry, ESH (2012). "Development of immunization trials against Klebsiella pneumoniae". Vaccine. 30 (14): 2411–2420. doi:10.1016/j.vaccine.2011.11.027. PMID 22100884.
- ^Podschun R, Ullmann U (1998). "Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors". Clin Microbiol Rev. 11 (4): 589–603. doi:10.1128/CMR.11.4.589. PMC 88898. PMID 9767057.
- ^Sieper, Joachim; Braun, Jürgen (2011). Ankylosing Spondylitis in Clinical Practice. London: Springer-Verlag. p. 9. ISBN . Retrieved October 10, 2012.
- ^Ahmad, TA; El-Sayed, LH; Haroun,M; Hussin, A; El-Ashry, ESH (2012). "Development of immunization trials against Klebsiella pneumoniae". Vaccine. 30 (14): 2411–2420. doi:10.1016/j.vaccine.2011.11.027. PMID 22100884.
- ^Ahmad, TA; El-Sayed, LH; Haroun,M; Hussin, A; El-Ashry, ESH (2012). "Development of a new trend conjugate vaccine for the prevention of Klebsiella pneumoniae". Infectious Disease Reports. 4 (2): e33. doi:10.4081/idr.2012.e33. PMC 3892636. PMID 24470947.
- ^Ogawa, Wakano; Li, Dai-Wei; Yu, Ping; Begum, Anowara; Mizushima, Tohru; Kuroda, Teruo; Tsuchiya, Tomofusa (2005). "Multidrug resistance in Klebsiella pneumoniae MGH78578 and cloning of genes responsible for the resistance". Biological & Pharmaceutical Bulletin. 28 (8): 1505–1508. doi:10.1248/bpb.28.1505. PMID 16079502.
- ^Jadhav, Savita; Rabindranath Misra; Nageshawari Gandham; Mahadev Ujagare; Purbasha Ghosh; Kalpana Angadi; Chanda Vyawahare (2012). "INCREASING INCIDENCE OF MULTIDRUG RESISTANCE klebsiella pneumoniae INFECTIONS IN HOSPITAL AND COMMUNITY SETTINGS". International Journal of Microbiology Research. 4 (6): 253–257. doi:10.9735/0975-52126.96.36.199-257.
- ^Davidson, Fraser W.; Whitney, Hugh G.; Tahlan, Kapil (2015-10-29). "Genome Sequences of Klebsiella variicola Isolates from Dairy Animals with Bovine Mastitis from Newfoundland, Canada". Genome Announcements. 3 (5): e00938–15. doi:10.1128/genomeA.00938-15. ISSN 2169-8287. PMC 4566169. PMID 26358587.
- ^Podder, Milka P.; Rogers, Laura; Daley, Peter K.; Keefe, Greg P.; Whitney, Hugh G.; Tahlan, Kapil (2014). "Klebsiella Species Associated with Bovine Mastitis in Newfoundland". PLOS ONE. 9 (9): e106518. Bibcode:2014PLoSO...9j6518P. doi:10.1371/journal.pone.0106518. PMC 4152263. PMID 25180510.
- ^Cakmaki ML, Evans HJ, Seidler RJ (1981). "Characteristics of a nitrogen-fixing Klebsiella oxytoca isolated from wheat roots". Plant and Soil. 61 (1–2): 53–64. doi:10.1007/BF02277362. S2CID 21625282.
- ^Haahtela, K; Laakso T; Korhonen TK (1986). "Associative nitrogen fixation by Klebsiella spp.: Adhesion sites and inoculation effects on grass roots". Applied and Environmental Microbiology. 52 (5): 1074–1079. Bibcode:1986ApEnM..52.1074H. doi:10.1128/aem.52.5.1074-1079.1986. PMC 239175. PMID 16347205.
- ^Riggs, PJ; Chelius MK; Iniguez AL; Kaeppler SM; Triplett EW (2001). "Enhanced maize productivity by inoculation with diazotrophic bacteria". Australian Journal of Plant Physiology. 28 (9): 829–836. doi:10.1071/PP01045.
- ^Fouts, Derrick E.; Tyler, Heather L.; Deboy, Robert T.; Daugherty, Sean; Ren, Qinghu; Badger, Jonathan H.; Durkin, Anthony S.; Huot, Heather; Shrivastava, Susmita; Kothari, Sagar; Dodson, Robert J.; Mohamoud, Yasmin; Khouri, Hoda; Roesch, Luiz F. W.; Krogfelt, Karen A.; Struve, Carsten; Triplett, Eric W.; Methé, Barbara A. (2008). "Complete Genome Sequence of the N2-Fixing Broad Host Range Endophyte Klebsiella pneumoniae 342 and Virulence Predictions Verified in Mice". PLOS Genetics. 4 (7): e1000141. doi:10.1371/journal.pgen.1000141. PMC 2453333. PMID 18654632.
- ^Rosenblueth, Mónica; Martínez, Lucía; Silva, Jesús; Martínez-Romero, Esperanza (2004-01-01). "Klebsiella variicola, A Novel Species with Clinical and Plant-Associated Isolates"(PDF). Systematic and Applied Microbiology. 27 (1): 27–35. doi:10.1078/0723-2020-00261. PMID 15053318. S2CID 40606728.
- ^Wei, Chun-Yan; Lin, Li; Luo, Li-Jing; Xing, Yong-Xiu; Hu, Chun-Jin; Yang, Li-Tao; Li, Yang-Rui; An, Qianli (2013-11-19). "Endophytic nitrogen-fixing Klebsiella variicola strain DX120E promotes sugarcane growth". Biology and Fertility of Soils. 50 (4): 657–666. doi:10.1007/s00374-013-0878-3. ISSN 0178-2762. S2CID 15594459.
- ^Pinto-Tomás, Adrián A.; Anderson, Mark A.; Suen, Garret; Stevenson, David M.; Chu, Fiona S. T.; Cleland, W. Wallace; Weimer, Paul J.; Currie, Cameron R. (2009-11-20). "Symbiotic Nitrogen Fixation in the Fungus Gardens of Leaf-Cutter Ants". Science. 326 (5956): 1120–1123. Bibcode:2009Sci...326.1120P. doi:10.1126/science.1173036. ISSN 0036-8075. PMID 19965433. S2CID 3119587.
You will also be interested:
- Toy gecko figurine
- Wella violet red
- Davita tri county
- True spike lug
- Control roku 2
- Videonow for sale
- Crepe clip art
- Cat meme yes
Larissa told me to call when I arrive in the city. her vagina. Her eyes flew open, lifted her head up, and pulled her scarlet tongue out of her mouth, white steam came out. It's more than it seems. She cried out with pleasure.