Nonlethal deleterious mutation-induced stress accelerates bacterial aging

• 成果类型: Article
• 署名作者: Kohram, Maryam; Sanderson, Amy E.; Loui, Alicia; Thompson, Peyton V.; Vashistha, Harsh; Shomar, Aseel; Oltvai, Zoltan N.; Salman, Hanna
• 署名单位: Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Technion Israel Institute of Technology; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; University of Rochester; Princeton University; Yale University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14432
• DOI: 10.1073/pnas.2316271121
• 发表日期: 2024-05-14
• 关键词: escherichia-coli; rpos mutations; segregation; resistance; mechanism; EVOLUTION; DYNAMICS; synthase; yeast; AGE

摘要

Random mutagenesis, including when it leads to loss of gene function, is a key mechanism enabling microorganisms' long - term adaptation to new environments. However, lossof - 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 alpha- subunit deleted ( Delta atpA ) 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 Delta atpA 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.