Extended-spectrum beta-lactamase (ESBL)-producing and non-ESBL-producing <i>Escherichia coli</i> isolates causing bacteremia in the Netherlands (2014 – 2016) differ in clonal distribution, antimicrobial resistance gene and virulence gene content

Hout, Denise van; Verschuuren, Tess D.; Bruijning-Verhagen, Patricia; Bosch, Thijs; Schürch, Anita C.; Willems, Rob J. L.; Bonten, Marc J. M.; Kluytmans, Jan

doi:10.1101/723734

Cited by 11 publications

(12 citation statements)

References 35 publications

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“…Short-read sequencing was performed using the Illumina HiSeq 2500/3000/4000/MiSeq instruments as previously described 18 . Additional, publicly available short-read sequencing data was obtained to facilitate phylogenetic comparison with previous studies 7,11,19,20 (BioProject accessions: PRJNA480723, PRJEB4681, PRJEB35000, PRJEB12513).…”

Section: Methodsmentioning

confidence: 99%

Molecular epidemiology of Escherichia coli and Klebsiella species bloodstream infections in Oxfordshire (UK) 2008-2018

Lipworth

Vihta

Chau

et al. 2021

Preprint

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The incidence of Gram-negative bloodstream infections (BSIs), predominantly caused by Escherichia coli and Klebsiella species, continues to increase; however the causes of this are unclear and effective interventions are therefore hard to design. In this study we sequenced 3468 sequential, unselected isolates over a decade in Oxfordshire, UK. We demonstrate that the observed increases in E. coli incidence were not driven by clonal expansion; instead, four major sequence types (STs) continue to dominate a stable population structure, with no evidence of adaptation to hospital/community settings. Conversely in Klebsiella spp. most infections are caused by sporadic STs with the exception of a local drug-resistant outbreak strain (ST490). Virulence elements are highly structured by ST in E. coli but not Klebsiella spp. where they occur in a diverse spectrum of STs and equally across healthcare and community settings. Most clinically hypervirulent (i.e. community-onset) Klebsiella BSIs have no known acquired virulence loci. Finally we demonstrate a diverse but largely genus-restricted mobilome with close associations between antimicrobial resistance (AMR) genes and insertion sequences but not typically specific plasmid replicon types; consistent with the dissemination of AMR genes being highly contingent on smaller mobile genetic elements (MGEs). Our large genomic study highlights distinct differences in the molecular epidemiology of E. coli and Klebsiella BSIs, and suggests that no single specific pathogen genetic factors are likely contributing to the increasing incidence of BSI overall, that association with AMR genes in E. coli is a contributor to the increasing number of E. coli BSIs, and that more attention should be given to AMR gene associations with non-plasmid MGEs to try and understand horizontal gene transfer networks.

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Section: Methodsmentioning

confidence: 99%

Molecular epidemiology of Escherichia coli and Klebsiella species bloodstream infections in Oxfordshire (UK) 2008-2018

Lipworth

Vihta

Chau

et al. 2021

Preprint

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“…To place our results in a global context, we additionally analysed 3678 isolates from existing studies selected to encompass the recent national/international longitudinal datasets available in the literature as well as isolates that were relatively rare in our collection (e.g. carbapenemase producing/genotypically hypervirulent isolates; data available through NCBI project accession numbers: PRJNA480723 16 , PRJEB4681 17 , PRJEB35000 18 , PRJEB12513 19 , PRJEB30913 20 , PRJEB1271 21 , PRJEB10018 22,23 ).…”

Section: Introductionmentioning

confidence: 99%

Ten Years of Population-Level Genomic Escherichia coli and Klebsiella pneumoniae Serotype Surveillance Informs Vaccine Development for Invasive Infections

Lipworth

Vihta

Chau

et al. 2021

Clinical Infectious Diseases

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Background The incidence of bloodstream infections (BSIs) caused by Escherichia coli and Klebsiella pneumoniae is increasing, with substantial associated morbidity, mortality and antimicrobial resistance. Unbiased serotyping studies to guide vaccine target selection are limited. Methods We conducted unselected, population-level genomic surveillance of bloodstream E. coli and Klebsiella pneumoniae isolates from 2008-2018 in Oxfordshire, UK. We supplemented this with an analysis of publicly available global sequencing data (n=3678). Results We sequenced 3478 E. coli isolates (3278 passed quality control) and 556 K. pneumoniae isolates (535 (K-antigen) and 549 (O-antigen) passed quality control). The four most common E. coli O-antigens (O1/O2/O6/O25) were identified in 1499/3278 isolates; the incidence of these O-types increased over time (IRRy=1.14, 95% CI:1.11-1.16). These O-types accounted for 616/1434 multidrug resistant (MDR) and 173/256 extended-spectrum beta-lactamase(ESBL)-resistant isolates in Oxfordshire, but only 19/90 carbapenem-resistant isolates across all studies. For Klebsiella pneumoniae, the most common O-antigens (O2v2/O1v1/O3b/O1v2) accounted for 410/549 isolates; the incidence of BSIs caused by these also increased annually (IRRy=1.09; 95% CI:1.05-1.12). These O-types accounted for 122/148 MDR and 106/123 ESBL isolates in Oxfordshire and 557/734 carbapenem-resistant isolates across all studies. Conversely we observed substantial capsular antigen diversity. Analysis of 3678 isolates from global studies demonstrated the generalisability of these findings. For E. coli, based on serotyping, the ExPEC4V and ExPEC10V vaccines under investigation would cover 46% and 72% of Oxfordshire isolates respectively, and 47% and 71% of MDR isolates. Conclusions O-antigen targeted vaccines may be useful in reducing the morbidity, mortality and antimicrobial resistance associated with E. coli and K. pneumoniae BSIs.

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“…In the urinary tract, E. coli causes a wide range of clinical syndromes that includes, from less to more severe, asymptomatic bacteriuria (ABU), bladder infection (cystitis), kidney infection (pyelonephritis), and urinary-source bacteremia. An estimated half of all E. coli bloodstream infections originate from the urinary tract [1][2][3] .…”

mentioning

confidence: 99%

Horizontally acquired papGII-containing pathogenicity islands underlie the emergence of invasive uropathogenic Escherichia coli lineages

et al. 2020

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Escherichia coli is the leading cause of urinary tract infection, one of the most common bacterial infections in humans. Despite this, a genomic perspective is lacking regarding the phylogenetic distribution of isolates associated with different clinical syndromes. Here, we present a large-scale phylogenomic analysis of a spatiotemporally and clinically diverse set of 907 E. coli isolates, including 722 uropathogenic E. coli (UPEC) isolates. A genome-wide association approach identifies the (P-fimbriae-encoding) papGII locus as the key feature distinguishing invasive UPEC, defined as isolates associated with severe UTI, i.e., kidney infection (pyelonephritis) or urinary-source bacteremia, from non-invasive UPEC, defined as isolates associated with asymptomatic bacteriuria or bladder infection (cystitis). Within the E. coli population, distinct invasive UPEC lineages emerged through repeated horizontal acquisition of diverse papGII-containing pathogenicity islands. Our findings elucidate the molecular determinants of severe UTI and have implications for the early detection of this pathogen.

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Extended-spectrum beta-lactamase (ESBL)-producing and non-ESBL-producing Escherichia coli isolates causing bacteremia in the Netherlands (2014 – 2016) differ in clonal distribution, antimicrobial resistance gene and virulence gene content

Cited by 11 publications

References 35 publications

Molecular epidemiology of Escherichia coli and Klebsiella species bloodstream infections in Oxfordshire (UK) 2008-2018

Molecular epidemiology of Escherichia coli and Klebsiella species bloodstream infections in Oxfordshire (UK) 2008-2018

Ten Years of Population-Level Genomic Escherichia coli and Klebsiella pneumoniae Serotype Surveillance Informs Vaccine Development for Invasive Infections

Horizontally acquired papGII-containing pathogenicity islands underlie the emergence of invasive uropathogenic Escherichia coli lineages

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