Tracking key virulence loci encoding aerobactin and salmochelin siderophore synthesis inKlebsiella pneumoniae

Abstract

ABSTRACTBackgroundKlebsiella pneumoniaeis a recognised agent of multidrug-resistant (MDR) healthcare-associated infections, however individual strains vary in their virulence potential due to the presence of mobile accessory genes. In particular, gene clusters encoding the biosynthesis of siderophores aerobactin (iuc) and salmochelin (iro) are associated with invasive disease and are common amongst hypervirulentK. pneumoniaeclones that cause severe community-associated infections such as liver abscess and pneumonia. Concerninglyiuchas also been reported in MDR strains in the hospital setting, where it was associated with increased mortality, highlighting the need to understand, detect and track the mobility of these virulence loci in theK. pneumoniaepopulation.MethodsHere we examined the genetic diversity, distribution and mobilisation ofiucandiroloci among 2503K. pneumoniaegenomes using comparative genomics approaches, and developed tools for tracking them via genomic surveillance.ResultsIroandiucwere detected at low prevalence (<10%). Considerable genetic diversity was observed, resolving into fiveiroand sixiuclineages that show distinct patterns of mobilisation and dissemination in theK. pneumoniaepopulation. The major burden ofiucandiroamongst the genomes analysed was due to two linked lineages (iuc1/iro1, 74% andiuc2/iro2, 14%), each carried by a distinct non-self-transmissible IncFIBKvirulence plasmid type that we designate KpVP-1 and KpVP-2. These dominant types also carry hypermucoidy (rmpA) determinants and include all previously described virulence plasmids ofK. pneumoniae. The otheriucandirolineages were associated with diverse plasmids, including some carrying FII conjugative transfer regions and some imported fromE. coli; the exceptions wereiro3(mobilised byICEKp1), andiuc4(fixed in the chromosome ofK. pneumoniaesubspeciesrhinoscleromatis).Iro/iucMGEs appear to be stably maintained at high frequency within known hypervirulent strains (ST23, ST86, etc), but were also detected at low prevalence in others such as MDR strain ST258.ConclusionsIucandiroare mobilised inK. pneumoniaevia a limited number of MGEs. This study provides a framework for identifying and tracking these important virulence loci, which will be important for genomic surveillance efforts including monitoring for the emergence of hypervirulent MDRK. pneumoniaestrains.