Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance inKlebsiella pneumoniae, an urgent threat to public health

Abstract

Klebsiella pneumoniaeis now recognized as an urgent threat to human health because of the emergence of multidrug-resistant strains associated with hospital outbreaks and hypervirulent strains associated with severe community-acquired infections.K.pneumoniaeis ubiquitous in the environment and can colonize and infect both plants and animals. However, little is known about the population structure ofK.pneumoniae, so it is difficult to recognize or understand the emergence of clinically important clones within this highly genetically diverse species. Here we present a detailed genomic framework forK.pneumoniaebased on whole-genome sequencing of more than 300 human and animal isolates spanning four continents. Our data provide genome-wide support for the splitting ofK.pneumoniaeinto three distinct species, KpI (K.pneumoniae), KpII (K.quasipneumoniae), and KpIII (K.variicola). Further, forK.pneumoniae(KpI), the entity most frequently associated with human infection, we show the existence of >150 deeply branching lineages including numerous multidrug-resistant or hypervirulent clones. We showK.pneumoniaehas a large accessory genome approaching 30,000 protein-coding genes, including a number of virulence functions that are significantly associated with invasive community-acquired disease in humans. In our dataset, antimicrobial resistance genes were common among human carriage isolates and hospital-acquired infections, which generally lacked the genes associated with invasive disease. The convergence of virulence and resistance genes potentially could lead to the emergence of untreatable invasiveK.pneumoniaeinfections; our data provide the whole-genome framework against which to track the emergence of such threats.