Diversification of colonization factors in a multidrug-resistant escherichia coli lineage evolving under negative frequency-dependent selection
Autor: | McNally, A, Kallonen, T, Connor, C, Abudahab, K, Aanensen, D, Horner, C, Peacock, S, Parkhill, J, Croucher, N, Corander, J |
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Přispěvatelé: | Wellcome Trust, Parkhill, Julian [0000-0002-7069-5958], Apollo - University of Cambridge Repository, Jukka Corander / Principal Investigator, Department of Mathematics and Statistics, Biostatistics Helsinki |
Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
Genotype
Extraintestinal Pathogenic Escherichia coli Virulence Factors evolutionary genomics Genetic Variation Ecological and Evolutionary Science Editor's Pick Microbiology QR1-502 Evolution Molecular Drug Resistance Multiple Bacterial 111 Mathematics Escherichia coli Humans AMR Selection Genetic negative frequency-dependent selection Escherichia coli Infections 0605 Microbiology Research Article |
Zdroj: | mBio mBio, Vol 10, Iss 2, p e00644-19 (2019) mBio, Vol 10, Iss 2 (2019) |
ISSN: | 2161-2129 |
DOI: | 10.1128/mbio.00644-19 |
Popis: | 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. 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. |
Databáze: | OpenAIRE |
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