Klebsiella pneumoniae (Kp) is an infamous cause of multi-drug resistant (MDR) healthcare-associated infections, for which several MDR clones are globally distributed. In the past 30 years a small number of drug-susceptible clones have also become globally distributed, causing severe community-acquired infections. These “hypervirulent” clones are distinguished by expression of the highly serum-resistant K1/K2 capsules, plus high prevalence of acquired virulence determinants. While hypervirulence and drug resistance are usually mutually exclusive in Kp, the last few years have seen increasing reports of convergent, virulent and MDR strains – a potentially disastrous combination.
To shed light on the evolutionary forces separating MDR and hypervirulence, and the drivers of convergence, we conducted a comparative genomic analysis of 28 distinct clones. We characterised antimicrobial resistance genes, virulence genes and capsule synthesis loci (K-loci). We also explored chromosomal recombination, plasmid, phage and pan-genome diversity.
As expected, there was substantial variation in the prevalence of resistance and virulence genes, and five of six hypervirulent clones were each associated with only one K-locus. Twenty of 22 remaining clones (including 8 MDR) harboured diverse K-loci, and subsequent recombination analyses indicated the K-locus was a major recombination hot spot. In contrast, chromosomal recombination was generally rare in the hypervirulent clones, which also showed reduced pan-genome diversity driven largely by restricted plasmid diversity. We hypothesised the hypervirulent clones may be limited in their ability to uptake DNA originating from other bacterial cells. We found no evidence that anti-DNA defence systems (CRISPR/Cas and restriction-modification systems) were driving these trends, but our analyses implicated physical inhibition of DNA uptake by the thick K1/K2 capsules.
We conclude that the majority of clones undergo frequent capsule exchange through homologous recombination, indicating that the capsule is subject to strong diversifying selective pressure, However, recombination is rare in the hypervirulent clones, which seem to be generally restricted in their ability to uptake DNA through physical inhibition by their thick serum resistant capsules.