Diversification of Colonization Factors in a Multidrug-Resistant <named-content content-type="genus-species">Escherichia coli</named-content> Lineage Evolving under Negative Frequency-Dependent Selection

ABSTRACT Escherichia coli is a major cause of bloodstream and urinary tract infections globally. The wide dissemination of multidrug-resistant (MDR) strains of extraintestinal pathogenic E. coli (ExPEC) poses a rapidly increasing public health burden due to narrowed treatment options and increased r...

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Autores principales: Alan McNally, Teemu Kallonen, Christopher Connor, Khalil Abudahab, David M. Aanensen, Carolyne Horner, Sharon J. Peacock, Julian Parkhill, Nicholas J. Croucher, Jukka Corander
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Publicado: American Society for Microbiology 2019
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Acceso en línea:https://doaj.org/article/6edd90209edf4b91aca6e2d94a4f76d2
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spelling oai:doaj.org-article:6edd90209edf4b91aca6e2d94a4f76d22021-11-15T15:55:26ZDiversification of Colonization Factors in a Multidrug-Resistant <named-content content-type="genus-species">Escherichia coli</named-content> Lineage Evolving under Negative Frequency-Dependent Selection10.1128/mBio.00644-192150-7511https://doaj.org/article/6edd90209edf4b91aca6e2d94a4f76d22019-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00644-19https://doaj.org/toc/2150-7511ABSTRACT Escherichia coli is a major cause of bloodstream and urinary tract infections globally. The wide dissemination of multidrug-resistant (MDR) strains of extraintestinal pathogenic E. coli (ExPEC) poses a rapidly increasing public health burden due to narrowed treatment options and increased risk of failure to clear an infection. Here, we present a detailed population genomic analysis of the ExPEC ST131 clone, in which we seek explanations for its success as an emerging pathogenic strain beyond the acquisition of antimicrobial resistance (AMR) genes. We show evidence for evolution toward separate ecological niches for the main clades of ST131 and differential evolution of anaerobic metabolism, key colonization, and virulence factors. We further demonstrate that negative frequency-dependent selection acting across accessory loci is a major mechanism that has shaped the population evolution of this pathogen. IMPORTANCE Infections with multidrug-resistant (MDR) strains of Escherichia coli are a significant global public health concern. To combat these pathogens, we need a deeper understanding of how they evolved from their background populations. By understanding the processes that underpin their emergence, we can design new strategies to limit evolution of new clones and combat existing clones. By combining population genomics with modelling approaches, we show that dominant MDR clones of E. coli are under the influence of negative frequency-dependent selection, preventing them from rising to fixation in a population. Furthermore, we show that this selection acts on genes involved in anaerobic metabolism, suggesting that this key trait, and the ability to colonize human intestinal tracts, is a key step in the evolution of MDR clones of E. coli.Alan McNallyTeemu KallonenChristopher ConnorKhalil AbudahabDavid M. AanensenCarolyne HornerSharon J. PeacockJulian ParkhillNicholas J. CroucherJukka CoranderAmerican Society for MicrobiologyarticleAMREscherichia colievolutionary genomicsnegative frequency-dependent selectionMicrobiologyQR1-502ENmBio, Vol 10, Iss 2 (2019)
institution DOAJ
collection DOAJ
language EN
topic AMR
Escherichia coli
evolutionary genomics
negative frequency-dependent selection
Microbiology
QR1-502
spellingShingle AMR
Escherichia coli
evolutionary genomics
negative frequency-dependent selection
Microbiology
QR1-502
Alan McNally
Teemu Kallonen
Christopher Connor
Khalil Abudahab
David M. Aanensen
Carolyne Horner
Sharon J. Peacock
Julian Parkhill
Nicholas J. Croucher
Jukka Corander
Diversification of Colonization Factors in a Multidrug-Resistant <named-content content-type="genus-species">Escherichia coli</named-content> Lineage Evolving under Negative Frequency-Dependent Selection
description ABSTRACT Escherichia coli is a major cause of bloodstream and urinary tract infections globally. The wide dissemination of multidrug-resistant (MDR) strains of extraintestinal pathogenic E. coli (ExPEC) poses a rapidly increasing public health burden due to narrowed treatment options and increased risk of failure to clear an infection. Here, we present a detailed population genomic analysis of the ExPEC ST131 clone, in which we seek explanations for its success as an emerging pathogenic strain beyond the acquisition of antimicrobial resistance (AMR) genes. We show evidence for evolution toward separate ecological niches for the main clades of ST131 and differential evolution of anaerobic metabolism, key colonization, and virulence factors. We further demonstrate that negative frequency-dependent selection acting across accessory loci is a major mechanism that has shaped the population evolution of this pathogen. IMPORTANCE Infections with multidrug-resistant (MDR) strains of Escherichia coli are a significant global public health concern. To combat these pathogens, we need a deeper understanding of how they evolved from their background populations. By understanding the processes that underpin their emergence, we can design new strategies to limit evolution of new clones and combat existing clones. By combining population genomics with modelling approaches, we show that dominant MDR clones of E. coli are under the influence of negative frequency-dependent selection, preventing them from rising to fixation in a population. Furthermore, we show that this selection acts on genes involved in anaerobic metabolism, suggesting that this key trait, and the ability to colonize human intestinal tracts, is a key step in the evolution of MDR clones of E. coli.
format article
author Alan McNally
Teemu Kallonen
Christopher Connor
Khalil Abudahab
David M. Aanensen
Carolyne Horner
Sharon J. Peacock
Julian Parkhill
Nicholas J. Croucher
Jukka Corander
author_facet Alan McNally
Teemu Kallonen
Christopher Connor
Khalil Abudahab
David M. Aanensen
Carolyne Horner
Sharon J. Peacock
Julian Parkhill
Nicholas J. Croucher
Jukka Corander
author_sort Alan McNally
title Diversification of Colonization Factors in a Multidrug-Resistant <named-content content-type="genus-species">Escherichia coli</named-content> Lineage Evolving under Negative Frequency-Dependent Selection
title_short Diversification of Colonization Factors in a Multidrug-Resistant <named-content content-type="genus-species">Escherichia coli</named-content> Lineage Evolving under Negative Frequency-Dependent Selection
title_full Diversification of Colonization Factors in a Multidrug-Resistant <named-content content-type="genus-species">Escherichia coli</named-content> Lineage Evolving under Negative Frequency-Dependent Selection
title_fullStr Diversification of Colonization Factors in a Multidrug-Resistant <named-content content-type="genus-species">Escherichia coli</named-content> Lineage Evolving under Negative Frequency-Dependent Selection
title_full_unstemmed Diversification of Colonization Factors in a Multidrug-Resistant <named-content content-type="genus-species">Escherichia coli</named-content> Lineage Evolving under Negative Frequency-Dependent Selection
title_sort diversification of colonization factors in a multidrug-resistant <named-content content-type="genus-species">escherichia coli</named-content> lineage evolving under negative frequency-dependent selection
publisher American Society for Microbiology
publishDate 2019
url https://doaj.org/article/6edd90209edf4b91aca6e2d94a4f76d2
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