期刊
NATURE COMMUNICATIONS
卷 13, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-28141-x
关键词
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资金
- Fund for Scientific Research, Flanders (FWO) [12O1917N, 12O1922N, V428917N, 11C6812/4N]
- Federation of European Microbiological Societies [RG-2016-0052]
- Belgian American Educational Foundation [2016-E083]
- European Molecular Biology Organization (EMBO) [ALTF 3442017]
- Agency for Innovation by Science and Technology (IWT)
- FWO [1528318N, G0B2515N, G055517N]
- KU Leuven [C16/17/006]
- Flanders Institute for Biotechnology (VIB)
- Deutsche Forschungsgemeinschaft [278002225/RTG 2202]
- Dutch Research Council (NWO
- VIDI grant) [864.11.001]
Antibiotic persisters are phenotypic variants within an isogenic bacterial population that are transiently tolerant to antibiotic treatment. This study provides evidence that cytoplasmic acidification, amplified by a compromised respiratory complex I, can act as a signaling hub for perturbed metabolic homeostasis in antibiotic persisters.
Antibiotic persisters are phenotypic variants within an isogenic bacterial population that are transiently tolerant to antibiotic treatment. Here, the authors provide evidence that cytoplasmic acidification, amplified by a compromised respiratory complex I, can act as a signaling hub for perturbed metabolic homeostasis in antibiotic persisters. Antibiotic persistence describes the presence of phenotypic variants within an isogenic bacterial population that are transiently tolerant to antibiotic treatment. Perturbations of metabolic homeostasis can promote antibiotic persistence, but the precise mechanisms are not well understood. Here, we use laboratory evolution, population-wide sequencing and biochemical characterizations to identify mutations in respiratory complex I and discover how they promote persistence in Escherichia coli. We show that persistence-inducing perturbations of metabolic homeostasis are associated with cytoplasmic acidification. Such cytoplasmic acidification is further strengthened by compromised proton pumping in the complex I mutants. While RpoS regulon activation induces persistence in the wild type, the aggravated cytoplasmic acidification in the complex I mutants leads to increased persistence via global shutdown of protein synthesis. Thus, we propose that cytoplasmic acidification, amplified by a compromised complex I, can act as a signaling hub for perturbed metabolic homeostasis in antibiotic persisters.
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