Diversification of colonization factors in a multidrug-resistant escherichia coli lineage evolving under negative frequency-dependent selection

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 fa...

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Main Authors: McNally, A, Kallonen, T, Connor, C, Abudahab, K, Aanensen, D, Horner, C, Peacock, S, Parkhill, J, Croucher, N, Corander, J
Formato: Journal article
Idioma:English
Publicado: American Society for Microbiology 2019
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author McNally, A
Kallonen, T
Connor, C
Abudahab, K
Aanensen, D
Horner, C
Peacock, S
Parkhill, J
Croucher, N
Corander, J
author_facet McNally, A
Kallonen, T
Connor, C
Abudahab, K
Aanensen, D
Horner, C
Peacock, S
Parkhill, J
Croucher, N
Corander, J
author_sort McNally, A
collection OXFORD
description 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.
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spelling oxford-uuid:d0aa21be-c9e3-4398-b2e7-e7a8653f90f62022-03-27T07:51:35ZDiversification of colonization factors in a multidrug-resistant escherichia coli lineage evolving under negative frequency-dependent selectionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d0aa21be-c9e3-4398-b2e7-e7a8653f90f6EnglishSymplectic Elements at OxfordAmerican Society for Microbiology2019McNally, AKallonen, TConnor, CAbudahab, KAanensen, DHorner, CPeacock, SParkhill, JCroucher, NCorander, JEscherichia 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.
spellingShingle McNally, A
Kallonen, T
Connor, C
Abudahab, K
Aanensen, D
Horner, C
Peacock, S
Parkhill, J
Croucher, N
Corander, J
Diversification of colonization factors in a multidrug-resistant escherichia coli lineage evolving under negative frequency-dependent selection
title Diversification of colonization factors in a multidrug-resistant escherichia coli lineage evolving under negative frequency-dependent selection
title_full Diversification of colonization factors in a multidrug-resistant escherichia coli lineage evolving under negative frequency-dependent selection
title_fullStr Diversification of colonization factors in a multidrug-resistant escherichia coli lineage evolving under negative frequency-dependent selection
title_full_unstemmed Diversification of colonization factors in a multidrug-resistant escherichia coli lineage evolving under negative frequency-dependent selection
title_short Diversification of colonization factors in a multidrug-resistant escherichia coli lineage evolving under negative frequency-dependent selection
title_sort diversification of colonization factors in a multidrug resistant escherichia coli lineage evolving under negative frequency dependent selection
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