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

Runcharoen, Chakkaphan; Moradigaravand, Danesh; Blane, Beth; Paksanont, Suporn; Thammachote, Jeeranan; Anun, Suthatip; Parkhill, Julian; Chantratita, Narisara; Peacock, Sharon J.

doi:10.1186/s13073-017-0397-1

Cited by 70 publications

(49 citation statements)

References 43 publications

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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).…”

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confidence: 99%

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

Weingarten

Johnson

Conlan

et al. 2018

mBio

180

134

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The hospital environment is a potential reservoir of bacteria with plasmids conferring carbapenem resistance. Our Hospital Epidemiology Service routinely performs extensive sampling of high-touch surfaces, sinks, and other locations in the hospital. Over a 2-year period, additional sampling was conducted at a broader range of locations, including housekeeping closets, wastewater from hospital internal pipes, and external manholes. We compared these data with previously collected information from 5 years of patient clinical and surveillance isolates. Whole-genome sequencing and analysis of 108 isolates provided comprehensive characterization of bla KPC /bla NDM -positive isolates, enabling an in-depth genetic comparison. Strikingly, despite a very low prevalence of patient infections with bla KPC -positive organisms, all samples from the intensive care unit pipe wastewater and external manholes contained carbapenemase-producing organisms (CPOs), suggesting a vast, resilient reservoir. We observed a diverse set of species and plasmids, and we noted species and susceptibility profile differences between environmental and patient populations of CPOs. However, there were plasmid backbones common to both populations, highlighting a potential environmental reservoir of mobile elements that may contribute to the spread of resistance genes. Clear associations between patient and environmental isolates were uncommon based on sequence analysis and epidemiology, suggesting reasonable infection control compliance at our institution. Nonetheless, a probable nosocomial transmission of Leclercia sp. from the housekeeping environment to a patient was detected by this extensive surveillance. These data and analyses further our understanding of CPOs in the hospital environment and are broadly relevant to the design of infection control strategies in many infrastructure settings.IMPORTANCE Carbapenemase-producing organisms (CPOs) are a global concern because of the morbidity and mortality associated with these resistant Gramnegative bacteria. Horizontal plasmid transfer spreads the resistance mechanism to new bacteria, and understanding the plasmid ecology of the hospital environment can assist in the design of control strategies to prevent nosocomial infections. A 5-year genomic and epidemiological survey was undertaken to study the CPOs in the patient-accessible environment, as well as in the plumbing system removed from the patient. This comprehensive survey revealed a vast, unappreciated reservoir of CPOs in wastewater, which was in contrast to the low positivity rate in both the patient population and the patient-accessible environment. While there were few patient-environmental isolate associations, there were plasmid backbones common to both populations. These results are relevant to all hospitals for which CPO colonization may not yet be defined through extensive surveillance.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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

Weingarten

Johnson

Conlan

et al. 2018

mBio

180

134

View full text Add to dashboard Cite

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“…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).…”

Section: Ecological Rangementioning

confidence: 99%

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

Wyres

Holt

2018

Preprint

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Klebsiella pneumoniae is an opportunistic bacterial pathogen known for its high frequency and diversity of antimicrobial resistance (AMR) genes. In addition to being a significant clinical problem in its own right, K. pneumoniae is the species within which several new AMR genes were first discovered before spreading to other pathogens (e.g. carbapenem--resistance genes KPC, OXA--48 and NDM--1). Whilst K. pneumoniae's contribution to the overall AMR crisis is impossible to quantify, current evidence suggests it has a wider ecological distribution, significantly more varied DNA composition, greater AMR gene diversity and a higher plasmid burden than other Gram negative opportunists. Hence we propose it plays a key role in disseminating AMR genes from environmental microbes to clinically important pathogens.

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“…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).…”

Section: Crispr/cas and Restriction--modification Systemsmentioning

confidence: 99%

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

Wyres

Wick

Judd

et al. 2018

Preprint

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Klebsiella pneumoniae (Kp) has emerged as an important cause of two distinct public health threats: multi-drug resistant (MDR) healthcare--associated infections 1 and community--acquired invasive infections, particularly pyogenic liver abscess 2 . The majority of MDR hospital outbreaks are caused by a subset of Kp clones with a high prevalence of acquired antimicrobial resistance (AMR) genes, while the majority of community--acquired invasive infections are caused by 'hypervirulent' clones that rarely harbour acquired AMR genes but have high prevalence of key virulence loci 3-5 . Worryingly, the last few years have seen increasing reports of convergence of MDR and the key virulence genes within individual Kp strains 6 , but it is not yet clear whether these represent a transient phenomenon or a significant ongoing threat. Here we perform comparative genomic analyses for 28 distinct Kp clones, including 6 hypervirulent and 8 MDR, to better understand their evolutionary histories and the risks of convergence. We show that MDR clones are highly diverse with frequent chromosomal recombination and gene content variability that far exceeds that of the hypervirulent clones. Consequently, we predict a much greater risk of virulence gene acquisition by MDR Kp clones than of resistance gene acquisition by hypervirulent clones. Kp MDR evolution is largely driven through acquisition of AMR genes on diverse mobilisable plasmids 7 which are particularly prevalent among the subset of clones that have become globally disseminated and frequently cause hospital outbreaks 8 ; e.g. clonal group (CG) 258 which is implicated in global spread of the Kp carbapenemases 9 . Kp pathogenicity is driven by a wide array of interacting factors 10-12 that are present in all strains, including the type III fimbriae (mrk) and the surface polysaccharides (capsule and lipopolysaccharide (LPS)) 12,13 which exhibit antigenic variation between strains. The majority of hypervirulent Kp, distinguished clinically as causing invasive infections even outside the hospital setting 14 , are associated with just two 4,15 of the >130 predicted capsular serotypes 16 , K1 and K2, that are considered particularly antiphagocytic and serum resistant 15,17 . Hypervirulent Kp are also associated with high prevalence of several other key virulence factors; the rmpA/rmpA2 genes that upregulate capsule expression to generate hypermucoidy 18,19 ; the colibactin genotoxin that induces eukaryotic cell death and promotes invasion to the blood from the intestines 20,21 ; and the yersiniabactin, aerobactin and salmochelin siderophores that promote survival in the blood by enhancing iron sequestration 11,[22][23][24] . Yersiniabactin synthesis is encoded by the ybt locus, which is usually mobilised by an integrative, conjugative element known as ICEKp. It is present in 40% of the general Kp population and seems to be frequently acquired and lost from MDR clones 25 . Fourteen distinct ybt+ICEKp variants are recognised, one of which also carries the colibactin synthesis locus (c...

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

Cited by 70 publications

References 43 publications

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

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

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

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

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