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Long-term evolution of antibiotic tolerance in Pseudomonas aeruginosa lung infections

Abstract:

Pathogenic bacteria respond to antibiotic pressure with the evolution of resistance but survival can also depend on their ability to tolerate antibiotic treatment, known as tolerance. While a variety of resistance mechanisms and underlying genetics are well characterized in vitro and in vivo, an understanding of the evolution of tolerance, and how it interacts with resistance in situ is lacking. We assayed for tolerance and resistance in isolates of Pseudomonas aeruginosa from chronic cystic fibrosis lung infections spanning up to 40 years of evolution, with 3 clinically relevant antibiotics: meropenem, ciprofloxacin, and tobramycin. We present evidence that tolerance is under positive selection in the lung and that it can act as an evolutionary stepping stone to resistance. However, by examining evolutionary patterns across multiple patients in different clone types, a key result is that the potential for an association between the evolution of resistance and tolerance is not inevitable, and difficult to predict.

Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1093/evlett/qrad034

Authors


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Role:
Author
ORCID:
0000-0002-7030-040X
More by this author
Role:
Author
ORCID:
0000-0002-5759-9769


Publisher:
Oxford University Press
Journal:
Evolution Letters More from this journal
Volume:
7
Issue:
6
Pages:
389-400
Publication date:
2023-09-20
Acceptance date:
2023-08-02
DOI:
EISSN:
2056-3744
Pmid:
38045720


Language:
English
Keywords:
Pubs id:
1547273
Local pid:
pubs:1547273
Deposit date:
2023-12-11

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