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Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia

BACKGROUND: Klebsiella pneumoniae is a leading cause of bloodstream infection (BSI). Strains producing extended-spectrum beta-lactamases (ESBLs) or carbapenemases are considered global priority pathogens for which new treatment and prevention strategies are urgently required, due to severely limited...

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Autores principales: Wyres, Kelly L., Nguyen, To N. T., Lam, Margaret M. C., Judd, Louise M., van Vinh Chau, Nguyen, Dance, David A. B., Ip, Margaret, Karkey, Abhilasha, Ling, Clare L., Miliya, Thyl, Newton, Paul N., Lan, Nguyen Phu Huong, Sengduangphachanh, Amphone, Turner, Paul, Veeraraghavan, Balaji, Vinh, Phat Voong, Vongsouvath, Manivanh, Thomson, Nicholas R., Baker, Stephen, Holt, Kathryn E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966826/
https://www.ncbi.nlm.nih.gov/pubmed/31948471
http://dx.doi.org/10.1186/s13073-019-0706-y
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author Wyres, Kelly L.
Nguyen, To N. T.
Lam, Margaret M. C.
Judd, Louise M.
van Vinh Chau, Nguyen
Dance, David A. B.
Ip, Margaret
Karkey, Abhilasha
Ling, Clare L.
Miliya, Thyl
Newton, Paul N.
Lan, Nguyen Phu Huong
Sengduangphachanh, Amphone
Turner, Paul
Veeraraghavan, Balaji
Vinh, Phat Voong
Vongsouvath, Manivanh
Thomson, Nicholas R.
Baker, Stephen
Holt, Kathryn E.
author_facet Wyres, Kelly L.
Nguyen, To N. T.
Lam, Margaret M. C.
Judd, Louise M.
van Vinh Chau, Nguyen
Dance, David A. B.
Ip, Margaret
Karkey, Abhilasha
Ling, Clare L.
Miliya, Thyl
Newton, Paul N.
Lan, Nguyen Phu Huong
Sengduangphachanh, Amphone
Turner, Paul
Veeraraghavan, Balaji
Vinh, Phat Voong
Vongsouvath, Manivanh
Thomson, Nicholas R.
Baker, Stephen
Holt, Kathryn E.
author_sort Wyres, Kelly L.
collection PubMed
description BACKGROUND: Klebsiella pneumoniae is a leading cause of bloodstream infection (BSI). Strains producing extended-spectrum beta-lactamases (ESBLs) or carbapenemases are considered global priority pathogens for which new treatment and prevention strategies are urgently required, due to severely limited therapeutic options. South and Southeast Asia are major hubs for antimicrobial-resistant (AMR) K. pneumoniae and also for the characteristically antimicrobial-sensitive, community-acquired “hypervirulent” strains. The emergence of hypervirulent AMR strains and lack of data on exopolysaccharide diversity pose a challenge for K. pneumoniae BSI control strategies worldwide. METHODS: We conducted a retrospective genomic epidemiology study of 365 BSI K. pneumoniae from seven major healthcare facilities across South and Southeast Asia, extracting clinically relevant information (AMR, virulence, K and O antigen loci) using Kleborate, a K. pneumoniae-specific genomic typing tool. RESULTS: K. pneumoniae BSI isolates were highly diverse, comprising 120 multi-locus sequence types (STs) and 63 K-loci. ESBL and carbapenemase gene frequencies were 47% and 17%, respectively. The aerobactin synthesis locus (iuc), associated with hypervirulence, was detected in 28% of isolates. Importantly, 7% of isolates harboured iuc plus ESBL and/or carbapenemase genes. The latter represent genotypic AMR-virulence convergence, which is generally considered a rare phenomenon but was particularly common among South Asian BSI (17%). Of greatest concern, we identified seven novel plasmids carrying both iuc and AMR genes, raising the prospect of co-transfer of these phenotypes among K. pneumoniae. CONCLUSIONS: K. pneumoniae BSI in South and Southeast Asia are caused by different STs from those predominating in other regions, and with higher frequency of acquired virulence determinants. K. pneumoniae carrying both iuc and AMR genes were also detected at higher rates than have been reported elsewhere. The study demonstrates how genomics-based surveillance—reporting full molecular profiles including STs, AMR, virulence and serotype locus information—can help standardise comparisons between sites and identify regional differences in pathogen populations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13073-019-0706-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-69668262020-01-22 Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia Wyres, Kelly L. Nguyen, To N. T. Lam, Margaret M. C. Judd, Louise M. van Vinh Chau, Nguyen Dance, David A. B. Ip, Margaret Karkey, Abhilasha Ling, Clare L. Miliya, Thyl Newton, Paul N. Lan, Nguyen Phu Huong Sengduangphachanh, Amphone Turner, Paul Veeraraghavan, Balaji Vinh, Phat Voong Vongsouvath, Manivanh Thomson, Nicholas R. Baker, Stephen Holt, Kathryn E. Genome Med Research BACKGROUND: Klebsiella pneumoniae is a leading cause of bloodstream infection (BSI). Strains producing extended-spectrum beta-lactamases (ESBLs) or carbapenemases are considered global priority pathogens for which new treatment and prevention strategies are urgently required, due to severely limited therapeutic options. South and Southeast Asia are major hubs for antimicrobial-resistant (AMR) K. pneumoniae and also for the characteristically antimicrobial-sensitive, community-acquired “hypervirulent” strains. The emergence of hypervirulent AMR strains and lack of data on exopolysaccharide diversity pose a challenge for K. pneumoniae BSI control strategies worldwide. METHODS: We conducted a retrospective genomic epidemiology study of 365 BSI K. pneumoniae from seven major healthcare facilities across South and Southeast Asia, extracting clinically relevant information (AMR, virulence, K and O antigen loci) using Kleborate, a K. pneumoniae-specific genomic typing tool. RESULTS: K. pneumoniae BSI isolates were highly diverse, comprising 120 multi-locus sequence types (STs) and 63 K-loci. ESBL and carbapenemase gene frequencies were 47% and 17%, respectively. The aerobactin synthesis locus (iuc), associated with hypervirulence, was detected in 28% of isolates. Importantly, 7% of isolates harboured iuc plus ESBL and/or carbapenemase genes. The latter represent genotypic AMR-virulence convergence, which is generally considered a rare phenomenon but was particularly common among South Asian BSI (17%). Of greatest concern, we identified seven novel plasmids carrying both iuc and AMR genes, raising the prospect of co-transfer of these phenotypes among K. pneumoniae. CONCLUSIONS: K. pneumoniae BSI in South and Southeast Asia are caused by different STs from those predominating in other regions, and with higher frequency of acquired virulence determinants. K. pneumoniae carrying both iuc and AMR genes were also detected at higher rates than have been reported elsewhere. The study demonstrates how genomics-based surveillance—reporting full molecular profiles including STs, AMR, virulence and serotype locus information—can help standardise comparisons between sites and identify regional differences in pathogen populations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13073-019-0706-y) contains supplementary material, which is available to authorized users. BioMed Central 2020-01-16 /pmc/articles/PMC6966826/ /pubmed/31948471 http://dx.doi.org/10.1186/s13073-019-0706-y Text en © The Author(s). 2020 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
Wyres, Kelly L.
Nguyen, To N. T.
Lam, Margaret M. C.
Judd, Louise M.
van Vinh Chau, Nguyen
Dance, David A. B.
Ip, Margaret
Karkey, Abhilasha
Ling, Clare L.
Miliya, Thyl
Newton, Paul N.
Lan, Nguyen Phu Huong
Sengduangphachanh, Amphone
Turner, Paul
Veeraraghavan, Balaji
Vinh, Phat Voong
Vongsouvath, Manivanh
Thomson, Nicholas R.
Baker, Stephen
Holt, Kathryn E.
Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia
title Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia
title_full Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia
title_fullStr Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia
title_full_unstemmed Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia
title_short Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia
title_sort genomic surveillance for hypervirulence and multi-drug resistance in invasive klebsiella pneumoniae from south and southeast asia
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966826/
https://www.ncbi.nlm.nih.gov/pubmed/31948471
http://dx.doi.org/10.1186/s13073-019-0706-y
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