Convergent phenotypic evolution towards fosfomycin collateral sensitivity of Pseudomonas aeruginosa antibiotic-resistant mutants.
Journal
Microbial biotechnology
ISSN: 1751-7915
Titre abrégé: Microb Biotechnol
Pays: United States
ID NLM: 101316335
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
revised:
06
04
2021
received:
08
02
2021
accepted:
07
04
2021
pubmed:
8
5
2021
medline:
16
4
2022
entrez:
7
5
2021
Statut:
ppublish
Résumé
The rise of antibiotic resistance and the reduced amount of novel antibiotics support the need of developing novel strategies to fight infections, based on improving the use of the antibiotics we already have. Collateral sensitivity is an evolutionary trade-off associated with the acquisition of antibiotic resistance that can be exploited to tackle this relevant health problem. However, different works have shown that patterns of collateral sensitivity are not always conserved, thus precluding the exploitation of this evolutionary trade-off to fight infections. In this work, we identify a robust pattern of collateral sensitivity to fosfomycin in Pseudomonas aeruginosa antibiotic-resistant mutants, selected by antibiotics belonging to different structural families. We characterize the underlying mechanism of the collateral sensitivity observed, which is a reduced expression of the genes encoding the peptidoglycan-recycling pathway, which preserves the peptidoglycan synthesis in situations where its de novo synthesis is blocked, and a reduced expression of fosA, encoding a fosfomycin-inactivating enzyme. We propose that the identification of robust collateral sensitivity patterns, as well as the understanding of the molecular mechanisms behind these phenotypes, would provide valuable information to design evolution-based strategies to treat bacterial infections.
Identifiants
pubmed: 33960651
doi: 10.1111/1751-7915.13817
pmc: PMC8867969
doi:
Substances chimiques
Anti-Bacterial Agents
0
Peptidoglycan
0
Fosfomycin
2N81MY12TE
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
613-629Informations de copyright
© 2021 The Authors. Microbial Biotechnology published by Society for Applied Microbiology and John Wiley & Sons Ltd.
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