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Variable recombination dynamics during the emergence, transmission and ‘disarming’ of a multidrug-resistant pneumococcal clone

BACKGROUND: Pneumococcal β-lactam resistance was first detected in Iceland in the late 1980s, and subsequently peaked at almost 25% of clinical isolates in the mid-1990s largely due to the spread of the internationally-disseminated multidrug-resistant PMEN2 (or Spain(6B)-2) clone of Streptococcus pn...

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Autores principales: Croucher, Nicholas J, Hanage, William P, Harris, Simon R, McGee, Lesley, van der Linden, Mark, de Lencastre, Herminia, Sá-Leão, Raquel, Song, Jae-Hoon, Ko, Kwan Soo, Beall, Bernard, Klugman, Keith P, Parkhill, Julian, Tomasz, Alexander, Kristinsson, Karl G, Bentley, Stephen D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4094930/
https://www.ncbi.nlm.nih.gov/pubmed/24957517
http://dx.doi.org/10.1186/1741-7007-12-49
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author Croucher, Nicholas J
Hanage, William P
Harris, Simon R
McGee, Lesley
van der Linden, Mark
de Lencastre, Herminia
Sá-Leão, Raquel
Song, Jae-Hoon
Ko, Kwan Soo
Beall, Bernard
Klugman, Keith P
Parkhill, Julian
Tomasz, Alexander
Kristinsson, Karl G
Bentley, Stephen D
author_facet Croucher, Nicholas J
Hanage, William P
Harris, Simon R
McGee, Lesley
van der Linden, Mark
de Lencastre, Herminia
Sá-Leão, Raquel
Song, Jae-Hoon
Ko, Kwan Soo
Beall, Bernard
Klugman, Keith P
Parkhill, Julian
Tomasz, Alexander
Kristinsson, Karl G
Bentley, Stephen D
author_sort Croucher, Nicholas J
collection PubMed
description BACKGROUND: Pneumococcal β-lactam resistance was first detected in Iceland in the late 1980s, and subsequently peaked at almost 25% of clinical isolates in the mid-1990s largely due to the spread of the internationally-disseminated multidrug-resistant PMEN2 (or Spain(6B)-2) clone of Streptococcus pneumoniae. RESULTS: Whole genome sequencing of an international collection of 189 isolates estimated that PMEN2 emerged around the late 1960s, developing resistance through multiple homologous recombinations and the acquisition of a Tn5253-type integrative and conjugative element (ICE). Two distinct clades entered Iceland in the 1980s, one of which had acquired a macrolide resistance cassette and was estimated to have risen sharply in its prevalence by coalescent analysis. Transmission within the island appeared to mainly emanate from Reykjavík and the Southern Peninsular, with evolution of the bacteria effectively clonal, mainly due to a prophage disrupting a gene necessary for genetic transformation in many isolates. A subsequent decline in PMEN2’s prevalence in Iceland coincided with a nationwide campaign that reduced dispensing of antibiotics to children in an attempt to limit its spread. Specific mutations causing inactivation or loss of ICE-borne resistance genes were identified from the genome sequences of isolates that reverted to drug susceptible phenotypes around this time. Phylogenetic analysis revealed some of these occurred on multiple occasions in parallel, suggesting they may have been at least temporarily advantageous. However, alteration of ‘core’ sequences associated with resistance was precluded by the absence of any substantial homologous recombination events. CONCLUSIONS: PMEN2’s clonal evolution was successful over the short-term in a limited geographical region, but its inability to alter major antigens or ‘core’ gene sequences associated with resistance may have prevented persistence over longer timespans.
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spelling pubmed-40949302014-07-15 Variable recombination dynamics during the emergence, transmission and ‘disarming’ of a multidrug-resistant pneumococcal clone Croucher, Nicholas J Hanage, William P Harris, Simon R McGee, Lesley van der Linden, Mark de Lencastre, Herminia Sá-Leão, Raquel Song, Jae-Hoon Ko, Kwan Soo Beall, Bernard Klugman, Keith P Parkhill, Julian Tomasz, Alexander Kristinsson, Karl G Bentley, Stephen D BMC Biol Research Article BACKGROUND: Pneumococcal β-lactam resistance was first detected in Iceland in the late 1980s, and subsequently peaked at almost 25% of clinical isolates in the mid-1990s largely due to the spread of the internationally-disseminated multidrug-resistant PMEN2 (or Spain(6B)-2) clone of Streptococcus pneumoniae. RESULTS: Whole genome sequencing of an international collection of 189 isolates estimated that PMEN2 emerged around the late 1960s, developing resistance through multiple homologous recombinations and the acquisition of a Tn5253-type integrative and conjugative element (ICE). Two distinct clades entered Iceland in the 1980s, one of which had acquired a macrolide resistance cassette and was estimated to have risen sharply in its prevalence by coalescent analysis. Transmission within the island appeared to mainly emanate from Reykjavík and the Southern Peninsular, with evolution of the bacteria effectively clonal, mainly due to a prophage disrupting a gene necessary for genetic transformation in many isolates. A subsequent decline in PMEN2’s prevalence in Iceland coincided with a nationwide campaign that reduced dispensing of antibiotics to children in an attempt to limit its spread. Specific mutations causing inactivation or loss of ICE-borne resistance genes were identified from the genome sequences of isolates that reverted to drug susceptible phenotypes around this time. Phylogenetic analysis revealed some of these occurred on multiple occasions in parallel, suggesting they may have been at least temporarily advantageous. However, alteration of ‘core’ sequences associated with resistance was precluded by the absence of any substantial homologous recombination events. CONCLUSIONS: PMEN2’s clonal evolution was successful over the short-term in a limited geographical region, but its inability to alter major antigens or ‘core’ gene sequences associated with resistance may have prevented persistence over longer timespans. BioMed Central 2014-06-23 /pmc/articles/PMC4094930/ /pubmed/24957517 http://dx.doi.org/10.1186/1741-7007-12-49 Text en Copyright © 2014 Croucher et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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 Article
Croucher, Nicholas J
Hanage, William P
Harris, Simon R
McGee, Lesley
van der Linden, Mark
de Lencastre, Herminia
Sá-Leão, Raquel
Song, Jae-Hoon
Ko, Kwan Soo
Beall, Bernard
Klugman, Keith P
Parkhill, Julian
Tomasz, Alexander
Kristinsson, Karl G
Bentley, Stephen D
Variable recombination dynamics during the emergence, transmission and ‘disarming’ of a multidrug-resistant pneumococcal clone
title Variable recombination dynamics during the emergence, transmission and ‘disarming’ of a multidrug-resistant pneumococcal clone
title_full Variable recombination dynamics during the emergence, transmission and ‘disarming’ of a multidrug-resistant pneumococcal clone
title_fullStr Variable recombination dynamics during the emergence, transmission and ‘disarming’ of a multidrug-resistant pneumococcal clone
title_full_unstemmed Variable recombination dynamics during the emergence, transmission and ‘disarming’ of a multidrug-resistant pneumococcal clone
title_short Variable recombination dynamics during the emergence, transmission and ‘disarming’ of a multidrug-resistant pneumococcal clone
title_sort variable recombination dynamics during the emergence, transmission and ‘disarming’ of a multidrug-resistant pneumococcal clone
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4094930/
https://www.ncbi.nlm.nih.gov/pubmed/24957517
http://dx.doi.org/10.1186/1741-7007-12-49
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