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Genomic evolution of Neisseria gonorrhoeae since the preantibiotic era (1928–2013): antimicrobial use/misuse selects for resistance and drives evolution

BACKGROUND: Multidrug-resistant Neisseria gonorrhoeae strains are prevalent, threatening gonorrhoea treatment globally, and understanding of emergence, evolution, and spread of antimicrobial resistance (AMR) in gonococci remains limited. We describe the genomic evolution of gonococci and their AMR,...

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Autores principales: Golparian, Daniel, Harris, Simon R., Sánchez-Busó, Leonor, Hoffmann, Steen, Shafer, William M., Bentley, Stephen D., Jensen, Jörgen S., Unemo, Magnus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6998845/
https://www.ncbi.nlm.nih.gov/pubmed/32013864
http://dx.doi.org/10.1186/s12864-020-6511-6
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author Golparian, Daniel
Harris, Simon R.
Sánchez-Busó, Leonor
Hoffmann, Steen
Shafer, William M.
Bentley, Stephen D.
Jensen, Jörgen S.
Unemo, Magnus
author_facet Golparian, Daniel
Harris, Simon R.
Sánchez-Busó, Leonor
Hoffmann, Steen
Shafer, William M.
Bentley, Stephen D.
Jensen, Jörgen S.
Unemo, Magnus
author_sort Golparian, Daniel
collection PubMed
description BACKGROUND: Multidrug-resistant Neisseria gonorrhoeae strains are prevalent, threatening gonorrhoea treatment globally, and understanding of emergence, evolution, and spread of antimicrobial resistance (AMR) in gonococci remains limited. We describe the genomic evolution of gonococci and their AMR, related to the introduction of antimicrobial therapies, examining isolates from 1928 (preantibiotic era) to 2013 in Denmark. This is, to our knowledge, the oldest gonococcal collection globally. METHODS: Lyophilised isolates were revived and examined using Etest (18 antimicrobials) and whole-genome sequencing (WGS). Quality-assured genome sequences were obtained for 191 viable and 40 non-viable isolates and analysed with multiple phylogenomic approaches. RESULTS: Gonococcal AMR, including an accumulation of multiple AMR determinants, started to emerge particularly in the 1950s–1970s. By the twenty-first century, resistance to most antimicrobials was common. Despite that some AMR determinants affect many physiological functions and fitness, AMR determinants were mainly selected by the use/misuse of gonorrhoea therapeutic antimicrobials. Most AMR developed in strains belonging to one multidrug-resistant (MDR) clade with close to three times higher genomic mutation rate. Modern N. gonorrhoeae was inferred to have emerged in the late-1500s and its genome became increasingly conserved over time. CONCLUSIONS: WGS of gonococci from 1928 to 2013 showed that no AMR determinants, except penB, were in detectable frequency before the introduction of gonorrhoea therapeutic antimicrobials. The modern gonococcus is substantially younger than previously hypothesized and has been evolving into a more clonal species, driven by the use/misuse of antimicrobials. The MDR gonococcal clade should be further investigated for early detection of strains with predispositions to develop and maintain MDR and for initiation of public health interventions.
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spelling pubmed-69988452020-02-10 Genomic evolution of Neisseria gonorrhoeae since the preantibiotic era (1928–2013): antimicrobial use/misuse selects for resistance and drives evolution Golparian, Daniel Harris, Simon R. Sánchez-Busó, Leonor Hoffmann, Steen Shafer, William M. Bentley, Stephen D. Jensen, Jörgen S. Unemo, Magnus BMC Genomics Research Article BACKGROUND: Multidrug-resistant Neisseria gonorrhoeae strains are prevalent, threatening gonorrhoea treatment globally, and understanding of emergence, evolution, and spread of antimicrobial resistance (AMR) in gonococci remains limited. We describe the genomic evolution of gonococci and their AMR, related to the introduction of antimicrobial therapies, examining isolates from 1928 (preantibiotic era) to 2013 in Denmark. This is, to our knowledge, the oldest gonococcal collection globally. METHODS: Lyophilised isolates were revived and examined using Etest (18 antimicrobials) and whole-genome sequencing (WGS). Quality-assured genome sequences were obtained for 191 viable and 40 non-viable isolates and analysed with multiple phylogenomic approaches. RESULTS: Gonococcal AMR, including an accumulation of multiple AMR determinants, started to emerge particularly in the 1950s–1970s. By the twenty-first century, resistance to most antimicrobials was common. Despite that some AMR determinants affect many physiological functions and fitness, AMR determinants were mainly selected by the use/misuse of gonorrhoea therapeutic antimicrobials. Most AMR developed in strains belonging to one multidrug-resistant (MDR) clade with close to three times higher genomic mutation rate. Modern N. gonorrhoeae was inferred to have emerged in the late-1500s and its genome became increasingly conserved over time. CONCLUSIONS: WGS of gonococci from 1928 to 2013 showed that no AMR determinants, except penB, were in detectable frequency before the introduction of gonorrhoea therapeutic antimicrobials. The modern gonococcus is substantially younger than previously hypothesized and has been evolving into a more clonal species, driven by the use/misuse of antimicrobials. The MDR gonococcal clade should be further investigated for early detection of strains with predispositions to develop and maintain MDR and for initiation of public health interventions. BioMed Central 2020-02-03 /pmc/articles/PMC6998845/ /pubmed/32013864 http://dx.doi.org/10.1186/s12864-020-6511-6 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 Article
Golparian, Daniel
Harris, Simon R.
Sánchez-Busó, Leonor
Hoffmann, Steen
Shafer, William M.
Bentley, Stephen D.
Jensen, Jörgen S.
Unemo, Magnus
Genomic evolution of Neisseria gonorrhoeae since the preantibiotic era (1928–2013): antimicrobial use/misuse selects for resistance and drives evolution
title Genomic evolution of Neisseria gonorrhoeae since the preantibiotic era (1928–2013): antimicrobial use/misuse selects for resistance and drives evolution
title_full Genomic evolution of Neisseria gonorrhoeae since the preantibiotic era (1928–2013): antimicrobial use/misuse selects for resistance and drives evolution
title_fullStr Genomic evolution of Neisseria gonorrhoeae since the preantibiotic era (1928–2013): antimicrobial use/misuse selects for resistance and drives evolution
title_full_unstemmed Genomic evolution of Neisseria gonorrhoeae since the preantibiotic era (1928–2013): antimicrobial use/misuse selects for resistance and drives evolution
title_short Genomic evolution of Neisseria gonorrhoeae since the preantibiotic era (1928–2013): antimicrobial use/misuse selects for resistance and drives evolution
title_sort genomic evolution of neisseria gonorrhoeae since the preantibiotic era (1928–2013): antimicrobial use/misuse selects for resistance and drives evolution
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6998845/
https://www.ncbi.nlm.nih.gov/pubmed/32013864
http://dx.doi.org/10.1186/s12864-020-6511-6
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