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Impact of transient acquired hypermutability on the inter- and intra-species competitiveness of Pseudomonas aeruginosa.

Published version
Peer-reviewed

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Authors

Figueroa, Wendy 
Fan, Catherine 
Bényei, Éva Bernadett 

Abstract

Once acquired, hypermutation is unrelenting, and in the long-term, leads to impaired fitness due to its cumulative impact on the genome. This raises the question of why hypermutators arise so frequently in microbial ecosystems. In this work, we explore this problem by examining how the transient acquisition of hypermutability affects inter- and intra-species competitiveness, and the response to environmental insults such as antibiotic challenge. We do this by engineering Pseudomonas aeruginosa to allow the expression of an important mismatch repair gene, mutS, to be experimentally controlled over a wide dynamic range. We show that high levels of mutS expression induce genomic stasis (hypomutation), whereas lower levels of induction lead to progressively higher rates of mutation. Whole-genome sequence analyses confirmed that the mutational spectrum of the inducible hypermutator is similar to the distinctive profile associated with mutS mutants obtained from the airways of people with cystic fibrosis (CF). The acquisition of hypermutability conferred a distinct temporal fitness advantage over the wild-type P. aeruginosa progenitor strain, in both the presence and the absence of an antibiotic selection pressure. However, over a similar time-scale, acquisition of hypermutability had little impact on the population dynamics of P. aeruginosa when grown in the presence of a competing species (Staphylococcus aureus). These data indicate that in the short term, acquired hypermutability primarily confers a competitive intra-species fitness advantage.

Description

Acknowledgements: YYO was supported by the Government of Malaysia under a King’s Scholarship [BYDPA 2018]. Elements of the work described in this research article were also supported by funding from the UK Cystic Fibrosis Trust [SRC017]. WFC was supported by CONAcYT and the Cambridge Trusts. EBB is supported by a studentship from the Oliver Gatty Trust (Cambridge). RAF, AW, and CR are supported by the Wellcome Trust (107032AIA), the Botnar Foundation (6063), and the UK Cystic Fibrosis Trust (Innovation Hub grant 001). RAF is supported by the NIHR Cambridge Biomedical Research Centre, and Health Enterprise East.


Funder: Government of Malaysia King’s Scholarship (BYDPA 2018)


Funder: CONAcYT and Cambridge Trusts Scholarship


Funder: Oliver Gatty Trust Scholarship


Funder: Foundation Botnar (6063) and UK Cystic Fibrosis Trust (Innovation Hub grant 001)


Funder: Foundation Botnar (6063), UK Cystic Fibrosis Trust (Innovation Hub grant 001), NIHR Cambridge Biomedical Research Centre, and Health Enterprise East.

Keywords

Humans, Pseudomonas aeruginosa, Ecosystem, Anti-Bacterial Agents, Mutation, Cystic Fibrosis, Pseudomonas Infections

Journal Title

ISME J

Conference Name

Journal ISSN

1751-7362
1751-7370

Volume Title

17

Publisher

Oxford University Press (OUP)
Sponsorship
Cystic Fibrosis Trust (SRC-017)
Wellcome Trust (107032/B/15/Z)
YYO was supported by the Government of Malaysia under a King’s Scholarship [BYDPA 2018]. Elements of the work described in this research article were also supported by funding from the UK Cystic Fibrosis Trust [SRC017]. WFC was supported by CONAcYT and the Cambridge Trusts. EBB is supported by a studentship from the Oliver Gatty Trust (Cambridge). RAF, AW, and CR are supported by the Wellcome Trust (107032AIA), the Botnar Foundation (6063), and the UK Cystic Fibrosis Trust (Innovation Hub grant 001). RAF is supported by the NIHR Cambridge Biomedical Research Centre, and Health Enterprise East.