Population genomics of Klebsiella pneumoniae

Abstract

Klebsiella pneumoniae is a common cause of antimicrobial-resistant opportunistic infections in hospitalized patients. The species is naturally resistant to penicillins, and members of the population often carry acquired resistance to multiple antimicrobials. However, knowledge of K. pneumoniae ecology, population structure or pathogenicity is relatively limited. Over the past decade, K. pneumoniae has emerged as a major clinical and public health threat owing to increasing prevalence of healthcare-associated infections caused by multidrug-resistant strains producing extended-spectrum β-lactamases and/or carbapenemases. A parallel phenomenon of severe community-acquired infections caused by ‘hypervirulent’ K. pneumoniae has also emerged, associated with strains expressing acquired virulence factors. These distinct clinical concerns have stimulated renewed interest in K. pneumoniae research and particularly the application of genomics. In this Review, we discuss how genomics approaches have advanced our understanding of K. pneumoniae taxonomy, ecology and evolution as well as the diversity and distribution of clinically relevant determinants of pathogenicity and antimicrobial resistance. A deeper understanding of K. pneumoniae population structure and diversity will be important for the proper design and interpretation of experimental studies, for interpreting clinical and public health surveillance data and for the design and implementation of novel control strategies against this important pathogen.

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Fig. 1: Taxonomic position of Klebsiella pneumoniae.
Fig. 2: Klebsiella pneumoniae population structure and global problem clones.
Fig. 3: Geographical distribution of Klebsiella pneumoniae clones harbouring resistance to carbapenems and third-generation cephalosporins.
Fig. 4: Antimicrobial resistance in Klebsiella pneumoniae.

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Acknowledgements

The authors are supported by Monash University and the Viertel Foundation of Australia. The authors thank Ryan Wick for assistance in creating the phylogenetic tree shown in Fig. 1.

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The authors contributed equally to all aspects of the article.

Correspondence to Kathryn E. Holt.

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Kleborate: https://github.com/katholt/Kleborate

PathogenWatch: https://pathogen.watch/

Supplementary information

Glossary

Disability-adjusted life years

A measure of disease burden estimated as the number of years lost to ill-health, disability and/or death.

Problem clones

Klebsiella pneumoniae clones that are over-represented among human infection isolates.

Endophthalmitis

Inflammation of the eye, usually caused by bacterial or fungal infection.

Necrotizing fasciitis

An infection resulting in rapid death of the skin and soft tissues.

Hypervirulent

A term used to describe a clinical phenomenon of severe community-acquired Klebsiella pneumoniae disease, which is typically associated with the presence of a combination of multiple acquired virulence loci.

Core genes

Genes that are present in all members of a given species (or nearly all, typically ≥95%).

Accessory genes

Genes that are present in some members of a given species but not all (typically <95%).

Core-genome multilocus sequence typing

(cgMLST). A classification scheme and nomenclature based on nucleotide sequence variation in core genes (usually hundreds of genes).

Clones

A generic term used to describe subpopulations of Klebsiella pneumoniae strains with a recent common ancestor identified through allelic variation in core genes, either by multilocus sequence typing or core-genome multilocus sequence typing (specifically called ‘clonal groups’ or ‘CGs’) or by core-genome phylogenetics (specifically called ‘lineages’).

Integrative conjugative elements

(ICEs). Mobile pieces of DNA that encode the machinery required for their own integration and excision from the bacterial host chromosome and transfer between bacterial cells.

ESKAPE pathogens

The six most common causes of multidrug-resistant health-care-associated infection defined by the Infectious Diseases Society of America: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species.

Simpson diversity

A measure of diversity that considers the total number of distinct entities (species, sequence types and so on) as well as their relative abundance.

Minimum inhibitory concentration

(MIC). The lowest concentration of a compound (usually an antibiotic) that is able to inhibit growth of a given bacterial isolate.

Pathogenicity factors

Features encoded by loci that are present in all Klebsiella pneumoniae (although there may be important allelic variants) and required for ‘classical’ opportunistic infections.

K-locus

The capsule (K antigen) biosynthesis locus.

Rhinoscleromatis

A rare chronic infection characterized by granulomas (structure formed from a collection of white blood cells) in the upper airways.

O-loci

The outer lipopolysaccharide (O antigen) biosynthesis loci.

Virulence factors

Features encoded by accessory loci which are entirely absent from most Klebsiella pneumoniae but whose presence increases either disease severity or propensity to cause disease.

FIBK replicons

Plasmids of incompatibility type IncFIBK.

Hypermucoidy

A phenotypic state characterized by ‘sticky’ growth and identified by production of a viscous filament (≥5 mm) when a colony is stretched by a culture loop.

Psicose sugar

A monosaccharide molecule, also known as allulose.

Classical infections

A term used to refer to opportunistic healthcare-associated Klebsiella pneumoniae infections.

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Wyres, K.L., Lam, M.M.C. & Holt, K.E. Population genomics of Klebsiella pneumoniae. Nat Rev Microbiol (2020). https://doi.org/10.1038/s41579-019-0315-1

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