In recent years Klebsiella pneumoniae and its close relatives have been associated with two distinct and growing public health concerns: 1) hospital-acquired infections caused by multi-drug resistant strains and 2) community-acquired invasive disease caused by hypervirulent strains (of particular concern in Asia). Consequently, there has been a resurgence of interest in non-traditional infection control strategies targeting the Klebsiella polysaccharide capsule, such as vaccines, phage therapy and depolymerase treatments.
There are 77 immunologically distinct Klebsiella capsule types (K-types) defined by serological techniques. Capsule polysaccharide synthesis (cps) loci defining each of the 77 known K-types, plus two distinct loci from serologically non-typeable strains, were recently published. However, little is known about the true extent of capsule diversity within this genus.
We investigated cps diversity using a collection of 2562 Klebsiella genomes. Our combinatorial gene screening approach found 981 of the genomes failed to match the published cps loci references. Further investigation allowed the identification and annotation of 61 novel loci, increasing the total known cps diversity of Klebsiella by more than 70%.
Interestingly, our analyses also provided evidence of intra-clonal cps exchange, particularly among clonal groups (CGs) associated with multi-drug resistance. Genomic analyses revealed the cps locus to be a recombination hotspot in these CGs (11/258, 14/15 and 17/20) with recombination events varying from less than 20Kb to over 1Mb in length.
In contrast, the cps locus was not a recombination hotspot among hypervirulent CGs, which showed much lower cps diversity. These Klebsiella are associated with tough, highly serum-resistant capsules and we speculate that they are subject to distinct evolutionary pressures favouring cps locus stability.
Our data indicate extensive capsule diversity among Klebsiella spp. that has not been previously appreciated. Furthermore, we found differences in cps locus diversity between multi-drug resistant and hypervirulent CGs. These findings directly inform the design of infection control strategies targeting Klebsiella capsules.