Population Genomic Molecular Epidemiological Study of Macrolide-Resistant Streptococcus pyogenes in Iceland, 1995 to 2016: Identification of a Large Clonal Population with a pbp2x Mutation Conferring Reduced In Vitro β-Lactam Susceptibility
Publisher's version (útgefin grein) Resistance to macrolide antibiotics is a global concern in the treatment of Streptococcus pyogenes (group A Streptococcus [GAS]) infections. In Iceland, since the detection of the first macrolide-resistant isolate in 1998, three epidemic waves of macrolide-re...
Published in: | Journal of Clinical Microbiology |
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American Society for Microbiology
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Online Access: | https://hdl.handle.net/20.500.11815/2219 https://doi.org/10.1128/JCM.00638-20 |
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ftopinvisindi:oai:opinvisindi.is:20.500.11815/2219 2023-05-15T16:46:56+02:00 Population Genomic Molecular Epidemiological Study of Macrolide-Resistant Streptococcus pyogenes in Iceland, 1995 to 2016: Identification of a Large Clonal Population with a pbp2x Mutation Conferring Reduced In Vitro β-Lactam Susceptibility Southon, Sara B. Beres, Stephen B. Kachroo, Priyanka Saavedra, Matthew Ojeda Erlendsdóttir, Helga Haraldsson, Gunnsteinn Yerramilli, Prasanti Pruitt, Layne Zhu, Luchang Musser, James M. Kristinsson, Karl G. Læknadeild (HÍ) Faculty of Medicine (UI) Heilbrigðisvísindasvið (HÍ) School of Health Sciences (UI) Háskóli Íslands University of Iceland 2020-06-10 e00638-20 https://hdl.handle.net/20.500.11815/2219 https://doi.org/10.1128/JCM.00638-20 en eng American Society for Microbiology Journal of Clinical Microbiology;58(9) https://syndication.highwire.org/content/doi/10.1128/JCM.00638-20 Southon SB, Beres SB, Kachroo P, Saavedra MO, Erlendsdóttir H, Haraldsson G, Yerramilli P, Pruitt L, Zhu L, Musser JM, Kristinsson KG. 2020. Population genomic molecular epidemiological study of macrolide-resistant Streptococcus pyogenes in Iceland, 1995 to 2016: identification of a large clonal population with a pbp2x mutation conferring reduced in vitro β-lactam susceptibility. Journal of Clinical Microbiology 58:e00638-20. https://doi.org/10.1128/JCM.00638-20. 0095-1137 1098-660X (eISSN) https://hdl.handle.net/20.500.11815/2219 Journal of Clinical Microbiology doi:10.1128/JCM.00638-20 info:eu-repo/semantics/openAccess Antibiotic resistance Macrolides Molecular epidemiology Population genomics Streptococcus pyogenes Sýkingar Sýklalyf Erfðarannsóknir info:eu-repo/semantics/article 2020 ftopinvisindi https://doi.org/20.500.11815/2219 https://doi.org/10.1128/JCM.00638-20 2022-11-18T06:52:02Z Publisher's version (útgefin grein) Resistance to macrolide antibiotics is a global concern in the treatment of Streptococcus pyogenes (group A Streptococcus [GAS]) infections. In Iceland, since the detection of the first macrolide-resistant isolate in 1998, three epidemic waves of macrolide-resistant GAS infections have occurred, with peaks in 1999, 2004, and 2008. We conducted whole-genome sequencing of all 1,575 available GAS macrolide-resistant clinical isolates of all infection types collected at the national reference laboratory in Reykjavik, Iceland, from 1998 to 2016. Among 1,515 erythromycin-resistant isolates, 90.3% were of only three emm types, emm4 (n = 713), emm6 (n = 324), and emm12 (n = 332), with each being predominant in a distinct epidemic peak. The antibiotic efflux pump genes, mef(A) and msr(D), were present on chimeric mobile genetic elements in 99.3% of the macrolide-resistant isolates of these emm types. Of note, in addition to macrolide resistance, virtually all emm12 isolates had a single amino acid substitution in penicillin-binding protein PBP2X that conferred a 2-fold increased penicillin G and ampicillin MIC among the isolates tested. We conclude that each of the three large epidemic peaks of macrolide-resistant GAS infections occurring in Iceland since 1998 was caused by the emergence and clonal expansion of progenitor strains, with macrolide resistance being conferred predominantly by inducible Mef(A) and Msr(D) drug efflux pumps. The occurrence of emm12 strains with macrolide resistance and decreased beta-lactam susceptibility was unexpected and is of public health concern. This study was supported in part by the Fondren Foundation, Houston Methodist Hospital and Research Institute, and National Institutes of Health grants AI139369 and AI146771 (to J.M.M.). Peer Reviewed Article in Journal/Newspaper Iceland Opin vísindi (Iceland) Journal of Clinical Microbiology 58 9 |
institution |
Open Polar |
collection |
Opin vísindi (Iceland) |
op_collection_id |
ftopinvisindi |
language |
English |
topic |
Antibiotic resistance Macrolides Molecular epidemiology Population genomics Streptococcus pyogenes Sýkingar Sýklalyf Erfðarannsóknir |
spellingShingle |
Antibiotic resistance Macrolides Molecular epidemiology Population genomics Streptococcus pyogenes Sýkingar Sýklalyf Erfðarannsóknir Southon, Sara B. Beres, Stephen B. Kachroo, Priyanka Saavedra, Matthew Ojeda Erlendsdóttir, Helga Haraldsson, Gunnsteinn Yerramilli, Prasanti Pruitt, Layne Zhu, Luchang Musser, James M. Kristinsson, Karl G. Population Genomic Molecular Epidemiological Study of Macrolide-Resistant Streptococcus pyogenes in Iceland, 1995 to 2016: Identification of a Large Clonal Population with a pbp2x Mutation Conferring Reduced In Vitro β-Lactam Susceptibility |
topic_facet |
Antibiotic resistance Macrolides Molecular epidemiology Population genomics Streptococcus pyogenes Sýkingar Sýklalyf Erfðarannsóknir |
description |
Publisher's version (útgefin grein) Resistance to macrolide antibiotics is a global concern in the treatment of Streptococcus pyogenes (group A Streptococcus [GAS]) infections. In Iceland, since the detection of the first macrolide-resistant isolate in 1998, three epidemic waves of macrolide-resistant GAS infections have occurred, with peaks in 1999, 2004, and 2008. We conducted whole-genome sequencing of all 1,575 available GAS macrolide-resistant clinical isolates of all infection types collected at the national reference laboratory in Reykjavik, Iceland, from 1998 to 2016. Among 1,515 erythromycin-resistant isolates, 90.3% were of only three emm types, emm4 (n = 713), emm6 (n = 324), and emm12 (n = 332), with each being predominant in a distinct epidemic peak. The antibiotic efflux pump genes, mef(A) and msr(D), were present on chimeric mobile genetic elements in 99.3% of the macrolide-resistant isolates of these emm types. Of note, in addition to macrolide resistance, virtually all emm12 isolates had a single amino acid substitution in penicillin-binding protein PBP2X that conferred a 2-fold increased penicillin G and ampicillin MIC among the isolates tested. We conclude that each of the three large epidemic peaks of macrolide-resistant GAS infections occurring in Iceland since 1998 was caused by the emergence and clonal expansion of progenitor strains, with macrolide resistance being conferred predominantly by inducible Mef(A) and Msr(D) drug efflux pumps. The occurrence of emm12 strains with macrolide resistance and decreased beta-lactam susceptibility was unexpected and is of public health concern. This study was supported in part by the Fondren Foundation, Houston Methodist Hospital and Research Institute, and National Institutes of Health grants AI139369 and AI146771 (to J.M.M.). Peer Reviewed |
author2 |
Læknadeild (HÍ) Faculty of Medicine (UI) Heilbrigðisvísindasvið (HÍ) School of Health Sciences (UI) Háskóli Íslands University of Iceland |
format |
Article in Journal/Newspaper |
author |
Southon, Sara B. Beres, Stephen B. Kachroo, Priyanka Saavedra, Matthew Ojeda Erlendsdóttir, Helga Haraldsson, Gunnsteinn Yerramilli, Prasanti Pruitt, Layne Zhu, Luchang Musser, James M. Kristinsson, Karl G. |
author_facet |
Southon, Sara B. Beres, Stephen B. Kachroo, Priyanka Saavedra, Matthew Ojeda Erlendsdóttir, Helga Haraldsson, Gunnsteinn Yerramilli, Prasanti Pruitt, Layne Zhu, Luchang Musser, James M. Kristinsson, Karl G. |
author_sort |
Southon, Sara B. |
title |
Population Genomic Molecular Epidemiological Study of Macrolide-Resistant Streptococcus pyogenes in Iceland, 1995 to 2016: Identification of a Large Clonal Population with a pbp2x Mutation Conferring Reduced In Vitro β-Lactam Susceptibility |
title_short |
Population Genomic Molecular Epidemiological Study of Macrolide-Resistant Streptococcus pyogenes in Iceland, 1995 to 2016: Identification of a Large Clonal Population with a pbp2x Mutation Conferring Reduced In Vitro β-Lactam Susceptibility |
title_full |
Population Genomic Molecular Epidemiological Study of Macrolide-Resistant Streptococcus pyogenes in Iceland, 1995 to 2016: Identification of a Large Clonal Population with a pbp2x Mutation Conferring Reduced In Vitro β-Lactam Susceptibility |
title_fullStr |
Population Genomic Molecular Epidemiological Study of Macrolide-Resistant Streptococcus pyogenes in Iceland, 1995 to 2016: Identification of a Large Clonal Population with a pbp2x Mutation Conferring Reduced In Vitro β-Lactam Susceptibility |
title_full_unstemmed |
Population Genomic Molecular Epidemiological Study of Macrolide-Resistant Streptococcus pyogenes in Iceland, 1995 to 2016: Identification of a Large Clonal Population with a pbp2x Mutation Conferring Reduced In Vitro β-Lactam Susceptibility |
title_sort |
population genomic molecular epidemiological study of macrolide-resistant streptococcus pyogenes in iceland, 1995 to 2016: identification of a large clonal population with a pbp2x mutation conferring reduced in vitro β-lactam susceptibility |
publisher |
American Society for Microbiology |
publishDate |
2020 |
url |
https://hdl.handle.net/20.500.11815/2219 https://doi.org/10.1128/JCM.00638-20 |
genre |
Iceland |
genre_facet |
Iceland |
op_relation |
Journal of Clinical Microbiology;58(9) https://syndication.highwire.org/content/doi/10.1128/JCM.00638-20 Southon SB, Beres SB, Kachroo P, Saavedra MO, Erlendsdóttir H, Haraldsson G, Yerramilli P, Pruitt L, Zhu L, Musser JM, Kristinsson KG. 2020. Population genomic molecular epidemiological study of macrolide-resistant Streptococcus pyogenes in Iceland, 1995 to 2016: identification of a large clonal population with a pbp2x mutation conferring reduced in vitro β-lactam susceptibility. Journal of Clinical Microbiology 58:e00638-20. https://doi.org/10.1128/JCM.00638-20. 0095-1137 1098-660X (eISSN) https://hdl.handle.net/20.500.11815/2219 Journal of Clinical Microbiology doi:10.1128/JCM.00638-20 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/20.500.11815/2219 https://doi.org/10.1128/JCM.00638-20 |
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Journal of Clinical Microbiology |
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58 |
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9 |
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1766037026184888320 |