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 Spain6B-2) clone of Streptococcus pneu...
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Online Access: | http://nrs.harvard.edu/urn-3:HUL.InstRepos:12717422 https://doi.org/10.1186/1741-7007-12-49 |
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ftharvardudash:oai:dash.harvard.edu:1/12717422 2023-05-15T16:47:29+02:00 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 2014 application/pdf http://nrs.harvard.edu/urn-3:HUL.InstRepos:12717422 https://doi.org/10.1186/1741-7007-12-49 en_US eng BioMed Central doi:10.1186/1741-7007-12-49 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4094930/pdf/ BMC Biology Croucher, N. J., W. P. Hanage, S. R. Harris, L. McGee, M. van der Linden, H. de Lencastre, R. Sá-Leão, et al. 2014. “Variable recombination dynamics during the emergence, transmission and ‘disarming’ of a multidrug-resistant pneumococcal clone.” BMC Biology 12 (1): 49. doi:10.1186/1741-7007-12-49. http://dx.doi.org/10.1186/1741-7007-12-49. 1741-7007 http://nrs.harvard.edu/urn-3:HUL.InstRepos:12717422 Bacterial evolution Antibiotic resistance Recombination Mobile genetic elements Coalescent analysis Phylogeography Journal Article 2014 ftharvardudash https://doi.org/10.1186/1741-7007-12-49 2022-04-04T20:51:29Z 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 Spain6B-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. Version of Record Article in Journal/Newspaper Iceland Reykjavík Reykjavík Harvard University: DASH - Digital Access to Scholarship at Harvard Reykjavík BMC Biology 12 1 49 |
institution |
Open Polar |
collection |
Harvard University: DASH - Digital Access to Scholarship at Harvard |
op_collection_id |
ftharvardudash |
language |
English |
topic |
Bacterial evolution Antibiotic resistance Recombination Mobile genetic elements Coalescent analysis Phylogeography |
spellingShingle |
Bacterial evolution Antibiotic resistance Recombination Mobile genetic elements Coalescent analysis Phylogeography 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 |
topic_facet |
Bacterial evolution Antibiotic resistance Recombination Mobile genetic elements Coalescent analysis Phylogeography |
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 Spain6B-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. Version of Record |
format |
Article in Journal/Newspaper |
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 |
title |
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_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_sort |
variable recombination dynamics during the emergence, transmission and ‘disarming’ of a multidrug-resistant pneumococcal clone |
publisher |
BioMed Central |
publishDate |
2014 |
url |
http://nrs.harvard.edu/urn-3:HUL.InstRepos:12717422 https://doi.org/10.1186/1741-7007-12-49 |
geographic |
Reykjavík |
geographic_facet |
Reykjavík |
genre |
Iceland Reykjavík Reykjavík |
genre_facet |
Iceland Reykjavík Reykjavík |
op_relation |
doi:10.1186/1741-7007-12-49 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4094930/pdf/ BMC Biology Croucher, N. J., W. P. Hanage, S. R. Harris, L. McGee, M. van der Linden, H. de Lencastre, R. Sá-Leão, et al. 2014. “Variable recombination dynamics during the emergence, transmission and ‘disarming’ of a multidrug-resistant pneumococcal clone.” BMC Biology 12 (1): 49. doi:10.1186/1741-7007-12-49. http://dx.doi.org/10.1186/1741-7007-12-49. 1741-7007 http://nrs.harvard.edu/urn-3:HUL.InstRepos:12717422 |
op_doi |
https://doi.org/10.1186/1741-7007-12-49 |
container_title |
BMC Biology |
container_volume |
12 |
container_issue |
1 |
container_start_page |
49 |
_version_ |
1766037574729596928 |