A nationwide genomic study of clinical <i>Klebsiella pneumoniae</i> in Norway 2001-2015: Introduction and spread of ESBL facilitated by CG15 and CG307

Fostervold, Aasmund; Hetland, Marit Andrea Klokkhammer; Bakksjø, Ragna; Bernhoff, Eva; Holt, Kathryn E.; Samuelsen, Ørjan; Simonsen, Gunnar Skov; Sundsfjord, Arnfinn; Wyres, Kelly L.; Löhr, Iren Høyland

doi:10.1101/2021.07.16.452602

Cited by 3 publications

(1 citation statement)

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“…[13][14][15]17,18,[22][23][24] We have comprehensive knowledge of the prevalence and population structure of clinical ESBL-E isolates showing a dominance of CTX-M-group ESBL enzymes and the association with specific extraintestinal pathogenic E. coli (ExPEC) and multidrug-resistant K. pneumoniae high-risk clones. [25][26][27][28] Large-scale genomic studies have identified specific subclades of E. coli sequence type (ST) 131 and K. pneumoniae ST307 as major contributors to the increasing prevalence of ESBL infections. 25,27,29,30 Community-based studies from the Netherlands and Sweden also observed a predominance of ST131, but a high genetic diversity within the ESBL-Ec population.…”

Section: Introductionmentioning

confidence: 99%

Community carriage of ESBL-producingEscherichia coliandKlebsiella pneumoniae: A cross-sectional study of risk factors and comparative genomics of carriage and clinical isolates

Raffelsberger

Buczek

Svendsen

et al. 2022

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The global prevalence of infections caused by ESBL-producing Enterobacterales (ESBL-E) is increasing and for Escherichia coli observations indicate that this is partly driven by community-onset cases. The ESBL-E population structure in the community is scarcely described and data on risk factors for carriage are conflicting. Here, we report the prevalence and population structure of fecal ESBL-producing E. coli and Klebsiella pneumoniae (ESBL-Ec/Kp) in a general adult population, examine risk factors, and compare carriage isolates with contemporary clinical isolates. Fecal samples obtained from 4999 participants (54% women) ≥40 years in the seventh survey of the population-based Tromsø Study, Norway (2015-2016) were screened for ESBL-Ec/Kp. In addition, we included 118 ESBL-Ec clinical isolates from the Norwegian surveillance program in 2014. All ESBL-producing isolates were whole-genome sequenced. Risk factors associated with carriage were analyzed using multivariable logistic regression. ESBL-Ec gastrointestinal carriage prevalence was 3.3% (95%CI 2.8-3.9%, no sex difference) and 0.08% (0.02-0.20%) for ESBL-Kp. For ESBL-Ec, travel to Asia was the only independent risk factor (AOR 3.47, 95%CI 2.18-5.51). E. coli ST131 was most prevalent in both collections. However, the ST131 proportion was significantly lower in carriage (24%) vs. clinical isolates (58%, p<0.001). Carriage isolates were genetically more diverse with a higher proportion of phylogroup A (26% vs. 5%, p<0.001), indicating that ESBL gene acquisition occurs in a variety of E. coli lineages colonizing the gut. STs commonly related to extra-intestinal infections were more frequent in the clinical isolates also carrying a higher prevalence of antimicrobial resistance, which could indicate clone associated pathogenicity.

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Section: Introductionmentioning

confidence: 99%

Community carriage of ESBL-producingEscherichia coliandKlebsiella pneumoniae: A cross-sectional study of risk factors and comparative genomics of carriage and clinical isolates

Raffelsberger

Buczek

Svendsen

et al. 2022

Preprint

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Kaptive 2.0: updated capsule and lipopolysaccharide locus typing for the Klebsiella pneumoniae species complex

et al. 2022

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The outer polysaccharide capsule and lipopolysaccharide (LPS) antigens are key targets for novel control strategies targeting Klebsiella pneumoniae and related taxa from the K. pneumoniae species complex (KpSC), including vaccines, phage and monoclonal antibody therapies. Given the importance and growing interest in these highly diverse surface antigens, we had previously developed Kaptive, a tool for rapidly identifying and typing capsule (K) and outer LPS (O) loci from whole genome sequence data. Here, we report two significant updates, now freely available in Kaptive 2.0 (https://github.com/katholt/kaptive): (i) the addition of 16 novel K locus sequences to the K locus reference database following an extensive search of >17 000 KpSC genomes; and (ii) enhanced O locus typing to enable prediction of the clinically relevant O2 antigen (sub)types, for which the genetic determinants have been recently described. We applied Kaptive 2.0 to a curated dataset of >12 000 public KpSC genomes to explore for the first time, to the best of our knowledge, the distribution of predicted O (sub)types across species, sampling niches and clones, which highlighted key differences in the distributions that warrant further investigation. As the uptake of genomic surveillance approaches continues to expand globally, the application of Kaptive 2.0 will generate novel insights essential for the design of effective KpSC control strategies.

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Kaptive 2.0: updated capsule and LPS locus typing for the Klebsiella pneumoniae species complex

Wick

Judd

Holt

2021

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The outer polysaccharide capsule and lipopolysaccharide antigens are key targets for novel control strategies targeting Klebsiella pneumoniae and related taxa from the K. pneumoniae species complex (KpSC), including vaccines, phage and monoclonal antibody therapies. Given the importance and growing interest in these highly diverse surface antigens, we had previously developed Kaptive, a tool for rapidly identifying and typing capsule (K) and outer lipopolysaccharide (O) loci from whole genome sequence data. Here, we report two significant updates, now freely available in Kaptive 2.0 (github.com/katholt/kaptive); i) the addition of 16 novel K locus sequences to the K locus reference database following an extensive search of >17,000 KpSC genomes; and ii) enhanced O locus typing to enable prediction of the clinically relevant O2 antigen (sub)types, for which the genetic determinants have been recently described. We applied Kaptive 2.0 to a curated dataset of >12,000 public KpSC genomes to explore for the first time the distribution of predicted O (sub)types across species, sampling niches and clones, which highlighted key differences in the distributions that warrant further investigation. As the uptake of genomic surveillance approaches continues to expand globally, the application of Kaptive 2.0 will generate novel insights essential for the design of effective KpSC control strategies.Significance as a BioResource to the communityKlebsiella pneumoniae is a major cause of bacterial healthcare associated infections globally, with increasing rates of antimicrobial resistance, including strains with resistance to the drugs of last resort. The latter have therefore been flagged as priority pathogens for the development of novel control strategies.K. pneumoniae produce two key surface antigen sugars (capsular polysaccharide and lipopolysaccharide (LPS)) that are immunogenic and targets for novel controls such as a vaccines and phage therapy. However, there is substantial antigenic diversity in the population and relatively little is understood about the distribution of antigen types geographically and among strains causing different types of infections. Whereas laboratory-based antigen typing is difficult and rarely performed, information about the relevant synthesis loci can be readily extracted from whole genome sequence data. We have previously developed Kaptive, a freely available tool for rapid typing of Klebsiella capsule and LPS loci from genome sequences.Kaptive is now used widely in the global research community and has facilitated new insights into Klebsiella capsule and LPS diversity. Here we present an update to Kaptive facilitating i) the identification of 16 additional novel capsule loci, and ii) the prediction of immunologically relevant LPS O2 antigen subtypes. These updates will enable enhanced sero-epidemiological surveillance for K. pneumoniae, to inform the design of vaccines and other novel Klebsiella control strategies.Data summaryThe updated code and reference databases for Kaptive are available at https://github.com/katholt/KaptiveGenome accessions from which reference sequences of novel K loci were defined are listed in Supplementary Table 1, and genomes from which these loci were detected (along with the corresponding Kaptive output) are listed in Supplementary Table 2.Accessions for the genomes screened for O types/subtypes (along with the corresponding Kaptive output) are listed in Supplementary Table 3.The authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files.Repositories1.1RepositoriesGenome sequence from which the novel K locus KL182 was defined has been deposited under the accession JAJHNT000000000.

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A nationwide genomic study of clinical Klebsiella pneumoniae in Norway 2001-2015: Introduction and spread of ESBL facilitated by CG15 and CG307

Cited by 3 publications

References 42 publications

Community carriage of ESBL-producingEscherichia coliandKlebsiella pneumoniae: A cross-sectional study of risk factors and comparative genomics of carriage and clinical isolates

Community carriage of ESBL-producingEscherichia coliandKlebsiella pneumoniae: A cross-sectional study of risk factors and comparative genomics of carriage and clinical isolates

Kaptive 2.0: updated capsule and lipopolysaccharide locus typing for the Klebsiella pneumoniae species complex

Kaptive 2.0: updated capsule and LPS locus typing for the Klebsiella pneumoniae species complex

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