Population Structure of Multidrug-Resistant Klebsiella oxytoca within Hospitals across the United Kingdom and Ireland Identifies Sharing of Virulence and Resistance Genes with K. pneumoniae

Abstract

Klebsiella oxytoca, a member of the Enterobacteriaceae, is a gram-negative pathogenic bacterium of environmental origin, which can cause infection in healthcare settings. Outbreaks of multidrug-resistant K. oxytoca infection have been increasingly reported in hospitalized patients. Despite the growing importance of this pathogen, there is limited knowledge about the population structure and epidemiology of antimicrobial resistant K. oxytoca. We investigated the population structure and genomic basis of antimicrobial resistance of 41 multidrug resistant K. oxytoca isolates recovered from bloodstream infections across the UK and Ireland. Our results show that K. oxytoca has a highly diverse population, which is composed of several distinct clades, and we identified one recent expansion of a clone within our dataset. Although the K. oxytoca genomes are clearly distinct from the genomes of a global collection of Klebsiella pneumoniae complex, pre-dominantly composed of K. pneumoniae, we found evidence for sharing of core genes through recombination, as well as the exchange of accessory antimicrobial resistance and virulence factor genes between the species. Our findings also suggest that the different K. oxytoca clades have acquired antimicrobial resistance and virulence factor genes independently. This highlights the clinical and therapeutic importance of genetic flexibility in K. oxytoca and the relevance of this in its role as an opportunistic pathogen.

Preterm infants harbour diverse Klebsiella populations, including atypical species that encode and produce an array of antimicrobial resistance- and virulence-associated factors

“…A total of 40,605 genes were detected in the open pangenome: 2,769 of them constituted the core gene cluster, while the accessory cluster included 5,108 genes and the remaining 32,728 genes formed the strain-specific cluster. A PCA plot based on the accessory genes clustered strains into the three different species ( Figure 5c ), in agreement with our phylogenetic analysis of the core genes ( Supplementary Figure 3b ) and consistent with the findings of [75], who were able to split the three species (phylogroups) based on a pangenome analysis of fewer genomes.…”

Preterm infants harbour diverse Klebsiella populations, including atypical species that encode and produce an array of antimicrobial resistance- and virulence-associated factors

“…All six members of the complex can be differentiated by matrix-assisted laserdesorption ionization/time-of-flight mass spectrometry (MALDI-TOF MS) [75], but reference databases currently in routine clinical use lack reference spectra for the different species to allow identification beyond K. oxytoca. Consequently, reports on complex members other than K. oxytoca have only recently begun to appear in the literature [73][74][75][76][77]. The colonization of humans with K. oxytoca phylogroups has previously been associated with the genetic backgrounds of strains: Ko2 mainly inhabits Fig.…”

“…Infrastructure support was provided by the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre (BRC). This work used the computing resources of the UK MEDical BIOinformatics partnership -aggregation, integration, visualization and analysis of large, complex data (UK Med-Bio) -which was supported by the Medical Research Council (grant number MR/L01632X/1), CLIMB [76] and the…”

Atypical Klebsiella Species in a Third Level Hospital as Cause of Neonatal Infection

“…similipneumoniae (KpII-B), and K. variicola (KpIII) (6). At present, K. oxytoca can cause infection in healthcare settings, with outbreaks of multidrug-resistant infection being increasingly reported in hospitalized patients (7)(8)(9)(10)(11)(12). Moreover, for pediatric population, infections due to extended spectrum beta lactamase (ESBL)-resistant Enterobacteriaceae are an emerging problem (13).…”