Nonlethal deleterious mutation-induced stress accelerates bacterial aging.

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.

Effect of cage-change frequency on rodent breeding performance.

Many people who work in laboratory rodent breeding facilities believe that disrupting certain sensitive rodent lines will result in increased breeding failures and loss of newborn pups. To evaluate this hypothesis, the authors assessed the effect of cage-change frequency on the breeding performances of a mouse strain (C57BL/6NTac) and a rat stock (NTac:NIH-Whn) that were thought to be sensitive to disruption. As per recommendations in the Guide for the Care and Use of Laboratory Animals, personnel changed one half of the breeding cages weekly, regardless of the presence of newborn pups. The other breeding cages were also changed weekly, unless newborn pups were present, in which case the cages were not changed until the following week. The authors assessed breeding performance by calculating the production efficiency index (the total number of pups that survived to weaning divided by the total number of actively breeding females). Breeding performance did not differ significantly between rodents whose cages were changed weekly and those whose pups were not disturbed.