Klebsiella pneumoniae (Kp) is a leading cause of healthcare-associated infections that often have high levels of antimicrobial resistance. Adding to the burden of disease, some strains have also acquired genes for siderophores; iron-scavenging molecules that enhance virulence and survival within the host. Multiple siderophores exist in Kp, including yersiniabactin, aerobactin and salmochelin, encoded by the ybt, iuc and iro loci respectively. Given the widespread presence of these loci and their role in virulence, we investigated their presence, genetic diversity and mobilisation in 2500 Kp genomes.
The ybt locus was the most common, found in >1/3 of the genomes, many of which were healthcare-associated, multidrug-resistant (MDR) strains. It was significantly associated with invasive liver abscess (OR=28.6) and bloodstream infections (OR=4.1). We identified 17 diverse ybt phylogenetic lineages. The ybt locus is typically mobilised by a chromosomal integrative and conjugative element (ICEKp) that can transfer between strains. We identified 14 ICEKp variants, many associated with particular ybt lineages, plus a previously unidentified plasmid lineage revealing a novel means of ybt dissemination. The iro and iuc loci are typically found separately on large virulence plasmids, with three plasmid variants carrying distinct iro and iuc lineages. Hundreds of ybt, iro and iuc acquisition events were detected, including multiple acquisitions by the globally-disseminated, MDR clonal group 258.
Our results highlight the ease with which Kp strains acquire siderophore loci. Their increased presence in MDR healthcare-associated strains is highly concerning, as the convergence of virulence and MDR may lead to severe, untreatable Kp infections. This situation warrants careful monitoring. As such, we have developed siderophore sequence-typing schemes to aid public health surveillance efforts for tracking their evolution and spread in global Kp populations, and most importantly, for detecting novel pathogenic MDR lineages before they become problematic.