Whole genome sequencing reveals high-resolution epidemiological links between clinical and environmental Klebsiella pneumoniae

Abstract

Background Klebsiella pneumoniae is a gram-negative bacterial species capable of occupying a broad range of environmental and clinical habitats. Known as an opportunistic pathogen, it has recently become a major causative agent of clinical infections worldwide. Despite growing knowledge about the highly diverse population of K. pneumoniae, the evolution and clinical significance of environmental K. pneumoniae, as well as the relationship between clinical and environmental K. pneumoniae, are poorly defined.MethodsWe isolated and sequenced K. pneumoniae from in-patients in a single hospital in Thailand, as well as hospital sewage, and surrounding canals and farms within a 20-km radius.ResultsPhylogenetic analysis of 77 K. pneumoniae (48 clinical and 29 non-clinical isolates) demonstrated that the two groups were intermixed throughout the tree and in some cases resided in the same clade, suggesting recent divergence from a common ancestor. Phylogenetic comparison of the 77 Thai genomes with 286 K. pneumoniae from a global collection showed that Thai isolates were closely related to the clinical sub-population of the global collection, indicating that Thai clinical isolates belonged to globally circulating lineages. Dating of four Thai K. pneumoniae clades indicated that they emerged between 50 and 150 years ago. Despite their phylogenetic relatedness, virulence factors and β-lactamase resistance genes were more numerous in clinical than in environmental isolates. Our results indicate that clinical and environmental K. pneumoniae are closely related, but that hospitals may select for isolates with a more resistant and virulent genotype.ConclusionsThese findings highlight the clinical relevance of environmental K. pneumoniae isolates.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-017-0397-1) contains supplementary material, which is available to authorized users.

Genomic Analysis of Hospital Plumbing Reveals Diverse Reservoir of Bacterial Plasmids Conferring Carbapenem Resistance

“…There have been many publications of hospital environmental investigations during outbreaks and some during nonoutbreak periods (20,25,27,54,55). Findings from the 2011 bla KPC ϩ K. pneumoniae outbreak investigation at NIHCC led to changes in our infection control policies, such as implementation of environmental surveillance cultures in response to newly identified CPO carriers and surveillance testing of previously positive sites after remediation.…”

“…Those studies used PCR, pulsed-field gel electrophoresis (PFGE), and culture methods to track organisms and antimicrobial resistance genes. WGS was often performed only on a small number of isolates and plasmids in these studies (18,26,27), limiting the genomic resolution of the analysis. Additionally, there have been limited studies comparing wastewater MDROs with patient isolates (18,(28)(29)(30)(31).…”

Klebsiella pneumoniae as a key trafficker of drug resistance genes from environmental to clinically important bacteria

“…ESBL ST15 in cats and dogs [60][61][62], and hypervirulent ST23 or ST25 in horses, non--human primates and pigs [44,63,64]. Genomic comparisons of K. pneumoniae from diverse sources are rare but show little evidence of segregation between niches: in a global diversity study, 59 bovine isolates were distributed around the species phylogeny comprising mostly human isolates [9]; and a comparison of ESBL isolates from Thai hospitals and a local canal system indicated phylogenetic intermingling [65]. These data and others [49] confirm that at least some strains, including those recognised as globally distributed hospital pathogens [12], can move between and proliferate in multiple niches, providing opportunity for genetic exchange with a broad range of bacterial species (Fig 3B).…”

Distinct evolutionary dynamics of horizontal gene transfer in drug resistant and virulent clones ofKlebsiella pneumoniae

“…Only the single best hit was recorded for each region of each genome. In order to assess the DNA recipient potential of each genome, we also used BLASTn to screen a broader sample of the Kp population, comprising the 1124 representative non--redundant genomes from our curated collection as described above and previously 16 , plus a further 598 diverse Kp genomes published during the course of this project [103][104][105][106] . A putative donor-recipient pairing was considered compatible if the complete set of REases in the recipient genome were also present in the donor genome (we assume that genomes positive for an REase also carry the corresponding methyltransferase).…”