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Stress-Induced Mutagenesis, Gambler Cells, and Stealth Targeting Antibiotic-Induced Evolution.
- Source :
-
MBio [mBio] 2022 Jun 28; Vol. 13 (3), pp. e0107422. Date of Electronic Publication: 2022 Jun 06. - Publication Year :
- 2022
-
Abstract
- Mechanisms of evolution and evolution of antibiotic resistance are both fundamental and world health problems. Stress-induced mutagenesis defines mechanisms of mutagenesis upregulated by stress responses, which drive adaptation when cells are maladapted to their environments-when stressed. Work in mutagenesis induced by antibiotics had produced tantalizing clues but not coherent mechanisms. We review recent advances in antibiotic-induced mutagenesis that integrate how reactive oxygen species (ROS), the SOS and general stress responses, and multichromosome cells orchestrate a stress response-induced switch from high-fidelity to mutagenic repair of DNA breaks. Moreover, while sibling cells stay stable, a mutable "gambler" cell subpopulation is induced by differentially generated ROS, which signal the general stress response. We discuss other evolvable subpopulations and consider diverse evolution-promoting molecules as potential targets for drugs to slow evolution of antibiotic resistance, cross-resistance, and immune evasion. An FDA-approved drug exemplifies "stealth" evolution-slowing drugs that avoid selecting resistance to themselves or antibiotics.
Details
- Language :
- English
- ISSN :
- 2150-7511
- Volume :
- 13
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- MBio
- Publication Type :
- Academic Journal
- Accession number :
- 35658528
- Full Text :
- https://doi.org/10.1128/mbio.01074-22