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Tracking key virulence loci encoding aerobactin and salmochelin siderophore synthesis in Klebsiella pneumoniae

BACKGROUND: Klebsiella pneumoniae is a recognised agent of multidrug-resistant (MDR) healthcare-associated infections; however, individual strains vary in their virulence potential due to the presence of mobile accessory genes. In particular, gene clusters encoding the biosynthesis of siderophores a...

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Autores principales: Lam, Margaret M. C., Wyres, Kelly L., Judd, Louise M., Wick, Ryan R., Jenney, Adam, Brisse, Sylvain, Holt, Kathryn E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205773/
https://www.ncbi.nlm.nih.gov/pubmed/30371343
http://dx.doi.org/10.1186/s13073-018-0587-5
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author Lam, Margaret M. C.
Wyres, Kelly L.
Judd, Louise M.
Wick, Ryan R.
Jenney, Adam
Brisse, Sylvain
Holt, Kathryn E.
author_facet Lam, Margaret M. C.
Wyres, Kelly L.
Judd, Louise M.
Wick, Ryan R.
Jenney, Adam
Brisse, Sylvain
Holt, Kathryn E.
author_sort Lam, Margaret M. C.
collection PubMed
description BACKGROUND: Klebsiella pneumoniae is a recognised agent of multidrug-resistant (MDR) healthcare-associated infections; however, individual strains vary in their virulence potential due to the presence of mobile accessory genes. In particular, gene clusters encoding the biosynthesis of siderophores aerobactin (iuc) and salmochelin (iro) are associated with invasive disease and are common amongst hypervirulent K. pneumoniae clones that cause severe community-associated infections such as liver abscess and pneumonia. Concerningly, iuc has also been reported in MDR strains in the hospital setting, where it was associated with increased mortality, highlighting the need to understand, detect and track the mobility of these virulence loci in the K. pneumoniae population. METHODS: Here, we examined the genetic diversity, distribution and mobilisation of iuc and iro loci amongst 2503 K. pneumoniae genomes using comparative genomics approaches and developed tools for tracking them via genomic surveillance. RESULTS: Iro and iuc were detected at low prevalence (< 10%). Considerable genetic diversity was observed, resolving into five iro and six iuc lineages that show distinct patterns of mobilisation and dissemination in the K. pneumoniae population. The major burden of iuc and iro amongst the genomes analysed was due to two linked lineages (iuc1/iro1 74% and iuc2/iro2 14%), each carried by a distinct non-self-transmissible IncFIB(K) virulence plasmid type that we designate KpVP-1 and KpVP-2. These dominant types also carry hypermucoidy (rmpA) determinants and include all previously described virulence plasmids of K. pneumoniae. The other iuc and iro lineages were associated with diverse plasmids, including some carrying IncFII conjugative transfer regions and some imported from Escherichia coli; the exceptions were iro3 (mobilised by ICEKp1) and iuc4 (fixed in the chromosome of K. pneumoniae subspecies rhinoscleromatis). Iro/iuc mobile genetic elements (MGEs) appear to be stably maintained at high frequency within known hypervirulent strains (ST23, ST86, etc.) but were also detected at low prevalence in others such as MDR strain ST258. CONCLUSIONS: Iuc and iro are mobilised in K. pneumoniae via a limited number of MGEs. This study provides a framework for identifying and tracking these important virulence loci, which will be important for genomic surveillance efforts including monitoring for the emergence of hypervirulent MDR K. pneumoniae strains. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13073-018-0587-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-62057732018-10-31 Tracking key virulence loci encoding aerobactin and salmochelin siderophore synthesis in Klebsiella pneumoniae Lam, Margaret M. C. Wyres, Kelly L. Judd, Louise M. Wick, Ryan R. Jenney, Adam Brisse, Sylvain Holt, Kathryn E. Genome Med Research BACKGROUND: Klebsiella pneumoniae is a recognised agent of multidrug-resistant (MDR) healthcare-associated infections; however, individual strains vary in their virulence potential due to the presence of mobile accessory genes. In particular, gene clusters encoding the biosynthesis of siderophores aerobactin (iuc) and salmochelin (iro) are associated with invasive disease and are common amongst hypervirulent K. pneumoniae clones that cause severe community-associated infections such as liver abscess and pneumonia. Concerningly, iuc has also been reported in MDR strains in the hospital setting, where it was associated with increased mortality, highlighting the need to understand, detect and track the mobility of these virulence loci in the K. pneumoniae population. METHODS: Here, we examined the genetic diversity, distribution and mobilisation of iuc and iro loci amongst 2503 K. pneumoniae genomes using comparative genomics approaches and developed tools for tracking them via genomic surveillance. RESULTS: Iro and iuc were detected at low prevalence (< 10%). Considerable genetic diversity was observed, resolving into five iro and six iuc lineages that show distinct patterns of mobilisation and dissemination in the K. pneumoniae population. The major burden of iuc and iro amongst the genomes analysed was due to two linked lineages (iuc1/iro1 74% and iuc2/iro2 14%), each carried by a distinct non-self-transmissible IncFIB(K) virulence plasmid type that we designate KpVP-1 and KpVP-2. These dominant types also carry hypermucoidy (rmpA) determinants and include all previously described virulence plasmids of K. pneumoniae. The other iuc and iro lineages were associated with diverse plasmids, including some carrying IncFII conjugative transfer regions and some imported from Escherichia coli; the exceptions were iro3 (mobilised by ICEKp1) and iuc4 (fixed in the chromosome of K. pneumoniae subspecies rhinoscleromatis). Iro/iuc mobile genetic elements (MGEs) appear to be stably maintained at high frequency within known hypervirulent strains (ST23, ST86, etc.) but were also detected at low prevalence in others such as MDR strain ST258. CONCLUSIONS: Iuc and iro are mobilised in K. pneumoniae via a limited number of MGEs. This study provides a framework for identifying and tracking these important virulence loci, which will be important for genomic surveillance efforts including monitoring for the emergence of hypervirulent MDR K. pneumoniae strains. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13073-018-0587-5) contains supplementary material, which is available to authorized users. BioMed Central 2018-10-29 /pmc/articles/PMC6205773/ /pubmed/30371343 http://dx.doi.org/10.1186/s13073-018-0587-5 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Lam, Margaret M. C.
Wyres, Kelly L.
Judd, Louise M.
Wick, Ryan R.
Jenney, Adam
Brisse, Sylvain
Holt, Kathryn E.
Tracking key virulence loci encoding aerobactin and salmochelin siderophore synthesis in Klebsiella pneumoniae
title Tracking key virulence loci encoding aerobactin and salmochelin siderophore synthesis in Klebsiella pneumoniae
title_full Tracking key virulence loci encoding aerobactin and salmochelin siderophore synthesis in Klebsiella pneumoniae
title_fullStr Tracking key virulence loci encoding aerobactin and salmochelin siderophore synthesis in Klebsiella pneumoniae
title_full_unstemmed Tracking key virulence loci encoding aerobactin and salmochelin siderophore synthesis in Klebsiella pneumoniae
title_short Tracking key virulence loci encoding aerobactin and salmochelin siderophore synthesis in Klebsiella pneumoniae
title_sort tracking key virulence loci encoding aerobactin and salmochelin siderophore synthesis in klebsiella pneumoniae
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205773/
https://www.ncbi.nlm.nih.gov/pubmed/30371343
http://dx.doi.org/10.1186/s13073-018-0587-5
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