The diversity of Klebsiella pneumoniae surface polysaccharides

Follador, Rainer; Heinz, Eva; Wyres, Kelly L.; Ellington, Matthew J.; Kowarik, Michael; Thomson, Nicholas R.

doi:10.1099/mgen.0.000073

Cited by 206 publications

(315 citation statements)

References 81 publications

(129 reference statements)

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“…The same conclusion was drawn by the authors of the recent in silico epidemiology study 5 . The current high prevalence of O3b and the fact that this subtype has not been described earlier (neither among K. pneumoniae O3 nor among E. coli O9 serogroup isolates) suggests a recent emergence.…”

Section: Discussionsupporting

confidence: 83%

See 1 more Smart Citation

Discovery of monoclonal antibodies cross-reactive to novel subserotypes of K. pneumoniae O3

Guachalla¹,

Stojkovic

Hartl³

et al. 2017

Sci Rep

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Klebsiella pneumoniae is responsible for nosocomial infections causing significant morbidity and mortality. Treatment of newly emerging multi-drug resistant strains is hampered due to severely limited antibiotic choices. Passive immunization targeting LPS O-antigens has been proposed as an alternative therapeutic option, given the limited variability of Klebsiella O-antigens. Here we report that the O3 serogroup, previously considered to have uniform O-antigen built of mannan, represents three different subtypes differing in the number of mannose residues within the O-antigen repeating units. Genetic analysis of the genes encoding mannose polymerization revealed differences that underline the observed structural alterations. The O3 variants represent antigenically different types based on the different reactivity pattern of murine monoclonal antibodies raised against a K. pneumoniae O3 strain. Typing of a collection of K. pneumoniae O3 clinical isolates showed that strains expressing the novel O3b antigen, the tri-mannose form, were more prevalent than those having the penta-mannose form, traditionally called O3, while the tetra-mannose variant, termed here O3a, seems to be rare. A monoclonal antibody cross-reacting with all three O3 sub-serogroups was also selected and shown to bind to the surface of various K. pneumoniae strains expressing different O3 subtypes and capsular antigens.

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Section: Discussionsupporting

confidence: 83%

“…In addition, the two genotypes “O3 short” and “O3 long” of O3 rfb operons recently described by Follador et al . 5 are shown. Phylogenetic trees for WbdD ( b ) and WbdA ( c ) were calculated. …”

Section: Resultsmentioning

confidence: 99%

Discovery of monoclonal antibodies cross-reactive to novel subserotypes of K. pneumoniae O3

Guachalla¹,

Stojkovic

Hartl³

et al. 2017

Sci Rep

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“…Furthermore, the diversity is an order of magnitude greater than that recently described for Klebsiella LPS, the other major Klebsiella surface antigen (Follador et al , 2016). This suggests that the K-locus is subject to strong diversifying selection.…”

Section: Discussionmentioning

confidence: 66%

Identification of Klebsiella capsule synthesis loci from whole genome data

et al. 2016

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Klebsiella pneumoniae is a growing cause of healthcare-associated infections for which multi-drug resistance is a concern. Its polysaccharide capsule is a major virulence determinant and epidemiological marker. However, little is known about capsule epidemiology since serological typing is not widely accessible and many isolates are serologically non-typeable. Molecular typing techniques provide useful insights, but existing methods fail to take full advantage of the information in whole genome sequences. We investigated the diversity of the capsule synthesis loci (K-loci) among 2503 K. pneumoniae genomes. We incorporated analyses of full-length K-locus nucleotide sequences and also clustered protein-encoding sequences to identify, annotate and compare K-locus structures. We propose a standardized nomenclature for K-loci and present a curated reference database. A total of 134 distinct K-loci were identified, including 31 novel types. Comparative analyses indicated 508 unique protein-encoding gene clusters that appear to reassort via homologous recombination. Extensive intra- and inter-locus nucleotide diversity was detected among the wzi and wzc genes, indicating that current molecular typing schemes based on these genes are inadequate. As a solution, we introduce Kaptive, a novel software tool that automates the process of identifying K-loci based on full locus information extracted from whole genome sequences (https://github.com/katholt/Kaptive). This work highlights the extensive diversity of Klebsiella K-loci and the proteins that they encode. The nomenclature, reference database and novel typing method presented here will become essential resources for genomic surveillance and epidemiological investigations of this pathogen.

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“…Presently, sequencing of the capsule synthesis wzi genes has become mainstream, and at least 134 distinct K loci have been identified [77]. The most common capsule locus associated with hvKp is K1, followed by K2, K5 and K57 [42,65,74,[78][79][80][81][82].…”

Section: Defining Hvkp Genotype and Capsule Typementioning

confidence: 99%

Hypervirulent Klebsiella pneumoniae – clinical and molecular perspectives

2019

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Hypervirulent Klebsiella pneumoniae (hvKp) has emerged as a concerning global pathogen. hvKp is more virulent than classical K. pneumoniae (cKp) and capable of causing community‐acquired infections, often in healthy individuals. hvKp is carried in the gastrointestinal tract, which contributes to its spread in the community and healthcare settings. First recognized in Asia, hvKp arose as a leading cause of pyogenic liver abscesses. In the decades since, hvKp has spread globally and causes a variety of infections. In addition to liver abscesses, hvKp is distinct from cKp in its ability to metastasize to distant sites, including most commonly the eye, lung and central nervous system (CNS). hvKp has also been implicated in primary extrahepatic infections including bacteremia, pneumonia and soft tissue infections. The genetic determinants of hypervirulence are often found on large virulence plasmids as well as chromosomal mobile genetic elements which can be used as biomarkers to distinguish hvKp from cKp clinical isolates. These distinct virulence determinants of hvKp include up to four siderophore systems for iron acquisition, increased capsule production, K1 and K2 capsule types, and the colibactin toxin. Additionally, hvKp strains demonstrate hypermucoviscosity, a phenotypic description of hvKp in laboratory conditions that has become a distinguishing feature of many hypervirulent isolates. Alarmingly, multidrug‐resistant hypervirulent strains have emerged, creating a new challenge in combating this already dangerous pathogen.

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The diversity of Klebsiella pneumoniae surface polysaccharides

Cited by 206 publications

References 81 publications

Discovery of monoclonal antibodies cross-reactive to novel subserotypes of K. pneumoniae O3

Discovery of monoclonal antibodies cross-reactive to novel subserotypes of K. pneumoniae O3

Identification of Klebsiella capsule synthesis loci from whole genome data

Hypervirulent Klebsiella pneumoniae – clinical and molecular perspectives

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