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626. Mobile Genetic Element Dynamics of Co-Circulating Klebsiella pneumoniae Sequence Types Carrying blaKPC in Houston, Texas

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CR-Kpn) are a significant cause of hospital-associated infections. Class A β-lactamases, e.g., Klebsiella pneumoniae carbapenemases (KPCs), are major contributors to carbapenem resistance. Sequence type 258 (ST258) is the most common genetic li...

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Autores principales: Shropshire, William C, Dinh, An Q, Miller, William R, Ecklund, Heather, Wanger, Audrey, Tran, Truc T, Arias, Cesar A, Hanson, Blake
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811148/
http://dx.doi.org/10.1093/ofid/ofz360.694
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author Shropshire, William C
Dinh, An Q
Miller, William R
Ecklund, Heather
Wanger, Audrey
Tran, Truc T
Arias, Cesar A
Hanson, Blake
author_facet Shropshire, William C
Dinh, An Q
Miller, William R
Ecklund, Heather
Wanger, Audrey
Tran, Truc T
Arias, Cesar A
Hanson, Blake
author_sort Shropshire, William C
collection PubMed
description BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CR-Kpn) are a significant cause of hospital-associated infections. Class A β-lactamases, e.g., Klebsiella pneumoniae carbapenemases (KPCs), are major contributors to carbapenem resistance. Sequence type 258 (ST258) is the most common genetic lineage of CR-Kpn associated with bla(KPC) carriage. Recently, a newly emergent lineage ST307 has been identified within the Houston metropolitan region. The transmission of bla(KPC) and other antimicrobial resistance (AMR) genes is driven largely by exchange of mobile genetic elements (MGEs). We sought to describe the dynamics of horizontal gene transfer (HGT) in particular between co-circulating strains of ST307 and ST258. METHODS: Long-read sequencing technologies allow us to resolve plasmid sequences and their associated AMR genes as well as characterize a comprehensive range of MGEs enabling transmission of these clinically important resistance mechanisms. CR-Kpn isolates were collected as part of a study to describe CRE burden within a Houston metropolitan hospital system. The Oxford Nanopore Technology (ONT) GridION X5 was used for long-read sequencing with Illumina short-read data used to refine and generate high-quality, consensus assemblies. A custom bioinformatic pipeline was used to resolve plasmid structures and identify the genomic context of plasmids carrying bla(KPC) variants. RESULTS: 95 Kpn isolates were collected from May to December 2017. Phylogenetic and in silico MLST analysis revealed 38/95 (40%) and 35/95 (37%) were ST258 and ST307, respectively. 86% of Kpn isolates carried one or more IncF-type conjugative plasmids, which were the prime vectors for bla(KPC) intercellular transmission. Interestingly, we found similar AMR-harboring plasmids within ST258 and ST307 composed of mosaic, modular IS26 and Tn3-like transposase mediated elements that carried multiple AMR determinants including bla(KPC) variants (Figure 1). CONCLUSION: We were able to characterize mechanisms by which ST307 and ST258 lineages may transfer AMR determinants. There are clinically relevant implications to these HGT events that occur between these lineages as they may provide insights into how resistance differentially develops. [Image: see text] DISCLOSURES: All authors: No reported disclosures.
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spelling pubmed-68111482019-10-29 626. Mobile Genetic Element Dynamics of Co-Circulating Klebsiella pneumoniae Sequence Types Carrying blaKPC in Houston, Texas Shropshire, William C Dinh, An Q Miller, William R Ecklund, Heather Wanger, Audrey Tran, Truc T Arias, Cesar A Hanson, Blake Open Forum Infect Dis Abstracts BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CR-Kpn) are a significant cause of hospital-associated infections. Class A β-lactamases, e.g., Klebsiella pneumoniae carbapenemases (KPCs), are major contributors to carbapenem resistance. Sequence type 258 (ST258) is the most common genetic lineage of CR-Kpn associated with bla(KPC) carriage. Recently, a newly emergent lineage ST307 has been identified within the Houston metropolitan region. The transmission of bla(KPC) and other antimicrobial resistance (AMR) genes is driven largely by exchange of mobile genetic elements (MGEs). We sought to describe the dynamics of horizontal gene transfer (HGT) in particular between co-circulating strains of ST307 and ST258. METHODS: Long-read sequencing technologies allow us to resolve plasmid sequences and their associated AMR genes as well as characterize a comprehensive range of MGEs enabling transmission of these clinically important resistance mechanisms. CR-Kpn isolates were collected as part of a study to describe CRE burden within a Houston metropolitan hospital system. The Oxford Nanopore Technology (ONT) GridION X5 was used for long-read sequencing with Illumina short-read data used to refine and generate high-quality, consensus assemblies. A custom bioinformatic pipeline was used to resolve plasmid structures and identify the genomic context of plasmids carrying bla(KPC) variants. RESULTS: 95 Kpn isolates were collected from May to December 2017. Phylogenetic and in silico MLST analysis revealed 38/95 (40%) and 35/95 (37%) were ST258 and ST307, respectively. 86% of Kpn isolates carried one or more IncF-type conjugative plasmids, which were the prime vectors for bla(KPC) intercellular transmission. Interestingly, we found similar AMR-harboring plasmids within ST258 and ST307 composed of mosaic, modular IS26 and Tn3-like transposase mediated elements that carried multiple AMR determinants including bla(KPC) variants (Figure 1). CONCLUSION: We were able to characterize mechanisms by which ST307 and ST258 lineages may transfer AMR determinants. There are clinically relevant implications to these HGT events that occur between these lineages as they may provide insights into how resistance differentially develops. [Image: see text] DISCLOSURES: All authors: No reported disclosures. Oxford University Press 2019-10-23 /pmc/articles/PMC6811148/ http://dx.doi.org/10.1093/ofid/ofz360.694 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Shropshire, William C
Dinh, An Q
Miller, William R
Ecklund, Heather
Wanger, Audrey
Tran, Truc T
Arias, Cesar A
Hanson, Blake
626. Mobile Genetic Element Dynamics of Co-Circulating Klebsiella pneumoniae Sequence Types Carrying blaKPC in Houston, Texas
title 626. Mobile Genetic Element Dynamics of Co-Circulating Klebsiella pneumoniae Sequence Types Carrying blaKPC in Houston, Texas
title_full 626. Mobile Genetic Element Dynamics of Co-Circulating Klebsiella pneumoniae Sequence Types Carrying blaKPC in Houston, Texas
title_fullStr 626. Mobile Genetic Element Dynamics of Co-Circulating Klebsiella pneumoniae Sequence Types Carrying blaKPC in Houston, Texas
title_full_unstemmed 626. Mobile Genetic Element Dynamics of Co-Circulating Klebsiella pneumoniae Sequence Types Carrying blaKPC in Houston, Texas
title_short 626. Mobile Genetic Element Dynamics of Co-Circulating Klebsiella pneumoniae Sequence Types Carrying blaKPC in Houston, Texas
title_sort 626. mobile genetic element dynamics of co-circulating klebsiella pneumoniae sequence types carrying blakpc in houston, texas
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811148/
http://dx.doi.org/10.1093/ofid/ofz360.694
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