In recent years there has been a global emergence of hospital-acquired infections caused by carbapenem-resistant Klebsiella pneumoniae harbouring KPC beta-lactamases. These K. pneumoniae form a closely-related group, defined by multi-locus sequence typing as clonal complex (CC) 258 (sequence types (STs) 258, 11, and closely-related variants).
It has been suggested that a vaccine comprising immunogenic K. pneumoniae capsular polysaccharides may be effective in reducing disease incidence. However, there are >76 capsular variants (K-types) and little is known about variation within globally-distributed clones. A recent study of >80 CC258 representative genomes, predominantly from the United States, showed little diversity and identified just two distinct capsular biosynthesis loci (K-loci). Here we investigate the broader CC258 lineage and characterise novel K-loci using a geographically diverse set of 40 CC258 genomes.
Results: SNP-based recombination detection analyses identified several large genomic recombination events within our sample (up to ~741kb length). These analyses confirmed that isolates representing ST395, which differs from ST258 at 4 of 7 multi-locus sequence typing loci, should be considered as a member of this CC. SNP-based phylogenetic analyses, excluding putative recombinant genome regions, identified a highly clonal sub-lineage containing the ST258 representatives. In contrast, the ST11 representatives were more diverse. A total of 11 distinct K-loci were identified, each comprising a conserved set of genes in the 5’ and 3’ regions (6 and 1, respectively), and a highly variable central region (9 – 17 putative genes). Among the ST258 sub-lineage there were two distinct phylogenetic clusters characterised by distinct K-loci, as previously reported.
Conclusions: K-locus variability suggested a high degree of K-type diversity among the broader CC258 K. pneumoniae, likely resulting from genetic recombination at or around the K-locus. Given the variability and potential for capsular switching, vaccines targeting K. pneumoniae capsular polysaccharides may be of limited use against this drug-resistant clone.