Genomic analysis of the emergence and rapid global dissemination of the KPC-producing Klebsiella pneumoniae pandemic.

Multidrug-resistant Klebsiella pneumoniae producing the carbapenemase KPC have rapidly spread throughout the world, causing severe healthcare-associated infections with limited antimicrobial treatment options. Dissemination of KPC-producing K. pneumoniae is largely attributed to expansion of a single dominant strain, ST258. In this study, we explore phylogenetic relationships and evolution within ST258 and its clonal complex, CC11, using comparative whole genome sequence analysis of 167 isolates from 20 countries collected over 17 years. Our results show a common ST258 ancestor emerged around 1995 and likely obtained blaKPC prior to dissemination. Over the past two decades, ST258 has remained highly clonal despite divergence in the capsule polysaccharide synthesis locus. Characterization of outer membrane protein sequences revealed a profile unique to ST258, including a severely truncated OmpK35 and modified OmpK37. Our work illuminates potential genomic contributors to the pathogenic success of ST258, helps us better understand the global dissemination of this strain, and identifies genetic markers unique to ST258.