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

Abstract

Klebsiella pneumoniae is 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. pneumoniae is ubiquitous in the environment and can colonize and infect both plants and animals. However, little is known about the population structure of K. 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 for K. pneumoniae based on whole-genome sequencing of more than 300 human and animal isolates spanning four continents. Our data provide genome-wide support for the splitting of K. pneumoniae into three distinct species, KpI (K. pneumoniae), KpII (K. quasipneumoniae), and KpIII (K. variicola). Further, for K. 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 show K. pneumoniae has 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 invasive K. pneumoniae infections; our data provide the whole-genome framework against which to track the emergence of such threats.

Klebsiella variicola and Klebsiella quasipneumoniae with capacity to adapt to clinical and plant settings

“…12 Unlike K. variicola, K. quasipneumoniae has been described exclusively in hospital settings. 13 A recent genomic comparative study with a large number of Klebsiella genomes showed that the nif operon was detected in all the genomes of K. variicola, in half of those of K. quasipneumoniae, but only in one strain of K. pneumoniae. 13 Additionally, K. pneumoniae and K. variicola shared some virulence determinants that cause infections in humans.…”

“…13 A recent genomic comparative study with a large number of Klebsiella genomes showed that the nif operon was detected in all the genomes of K. variicola, in half of those of K. quasipneumoniae, but only in one strain of K. pneumoniae. 13 Additionally, K. pneumoniae and K. variicola shared some virulence determinants that cause infections in humans. 14,15 Some Klebsiella isolates have been misclassified 16,17 and consequently the taxonomic descriptions of their genome sequences in NCBI repositories are inaccurate.…”

“…The NifH protein has high amino acid identity among all K. variicola genomes and in a phylogenetic analysis it is grouped in a cluster different from the corresponding sequence from the K. quasipneumoniae or other species. Holt and colleagues 13 identified only one K. pneumoniae genome that contained the nifJ-nifQ operon. In this work, we identified another K. pneumoniae genome (from KPNIN29) that contains the nif operon in addition to that described by Holt and colleagues.…”

“…In this work, we identified another K. pneumoniae genome (from KPNIN29) that contains the nif operon in addition to that described by Holt and colleagues. 13 Hazen and colleagues 27 identified the absence of nifJ-nifQ gene cluster in K. pneumoniae NTUH-K2044, MGH-78578, 1162281, JH1, MS 92-3, 1191100241, ATCC13884 and KCTC-2242 genomes. Here we identified a conserved genetic context and gene synteny of nifJ-nifQ operon both in K. variicola and K. quasipneumoniae genomes (data not shown).…”

Detection of High Prevalence of TEM/SHV/CTX-M Genes in ESBL Producing and Multidrug Resistant Klebsiella Pneumoniae and Klebsiella Oxytoca

“…The first reported β-lactamases TEM-1/2 and SHV-1, described since 1960 from E. coli and Klebsiella pneumoniae were usually chromosomal. They are the most medically important species, often isolated from severe infections in hospitalized or ambulatory patients [25][26][27][28][29]. Klebsiella spp.…”