Nonlethal deleterious mutation-induced stress accelerates bacterial aging.

Autor:	Kohram M; Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, PA 15260., Sanderson AE; Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, PA 15260., Loui A; Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, PA 15260., Thompson PV; Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15260., Vashistha H; Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, PA 15260., Shomar A; Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel., Oltvai ZN; Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15260.; Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA 15260.; Department of Pathology and Laboratory Medicine, University of Rochester, Rochester, NY 14627., Salman H; Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, PA 15260.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 May 14; Vol. 121 (20), pp. e2316271121. Date of Electronic Publication: 2024 May 06.
DOI:	10.1073/pnas.2316271121
Abstrakt:	Random mutagenesis, including when it leads to loss of gene function, is a key mechanism enabling microorganisms' long-term adaptation to new environments. However, loss-of-function mutations are often deleterious, triggering, in turn, cellular stress and complex homeostatic stress responses, called "allostasis," to promote cell survival. Here, we characterize the differential impacts of 65 nonlethal, deleterious single-gene deletions on Escherichia coli growth in three different growth environments. Further assessments of select mutants, namely, those bearing single adenosine triphosphate (ATP) synthase subunit deletions, reveal that mutants display reorganized transcriptome profiles that reflect both the environment and the specific gene deletion. We also find that ATP synthase α-subunit deleted ( ΔatpA ) cells exhibit elevated metabolic rates while having slower growth compared to wild-type (wt) E. coli cells. At the single-cell level, compared to wt cells, individual ΔatpA cells display near normal proliferation profiles but enter a postreplicative state earlier and exhibit a distinct senescence phenotype. These results highlight the complex interplay between genomic diversity, adaptation, and stress response and uncover an "aging cost" to individual bacterial cells for maintaining population-level resilience to environmental and genetic stress; they also suggest potential bacteriostatic antibiotic targets and -as select human genetic diseases display highly similar phenotypes, - a bacterial origin of some human diseases. Competing Interests: Competing interests statement:The authors declare no competing interest.
Databáze:	MEDLINE
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