Gre factors protect against phenotypic diversification and cheating inEscherichia colipopulations under toxic metabolite stress

Abstract

AbstractNitric oxide (·NO) is one of the toxic metabolites that bacteria can be exposed to within phagosomes. Gre factors, which are also known as transcript cleavage factors or transcription elongation factors, relieve back-tracked transcription elongation complexes by cleaving nascent RNAs, which allows transcription to resume after stalling. Here we discovered that loss of both Gre factors inE. coli, GreA and GreB, significantly compromised ·NO detoxification through a phenotypic diversification of the population. Under normal culturing conditions, both wild-type and ΔgreAΔgreBsynthesized protein uniformly. However, treatment with ·NO led to bimodal protein expression in ΔgreAΔgreB, whereas wild-type remained unimodal. Interestingly, exposure to another toxic metabolite of phagosomes, hydrogen peroxide (H2O2), produced similar results. We found that the diversification in ΔgreAΔgreBcultures requiredE. coliRNAP, occurred at the level of transcription, and could produce cheating where transcriptionally-deficient cells benefit from the detoxification activities of the transcriptionally-proficient subpopulation. Collectively, these results indicate that Gre factors bolster bacterial defenses by preventing phenotypic diversification and cheating in environments with fast-diffusing toxic metabolites.ImportanceToxic metabolite stress occurs in a broad range of contexts that are important to human health, microbial ecology, and biotechnology; whereas Gre factors are highly conserved throughout the bacterial kingdom. Here we discovered that the Gre factors ofE. coliprevent phenotypic diversification under toxic metabolite stress. Such conformist regulation improves populationwide removal of those stressors and protects against cheating, where one subpopulation commits resources to counter a threat, and the other subpopulation does not, yet both subpopulations benefit.