The SOS Response Mediates Sustained Colonization of the Mammalian Gut

Abstract

Bacteria have a remarkable ability to survive, persist, and ultimately adapt to environmental challenges. A ubiquitous environmental hazard is DNA damage, and most bacteria have evolved a network of genes to combat genotoxic stress. This network is known as the SOS response and aids in bacterial survival by regulating genes involved in DNA repair and damage tolerance. Recently, the SOS response has been shown to play an important role in bacterial pathogenesis, and yet the role of the SOS response in nonpathogenic organisms and in physiological settings remains underexplored. Using a commensal Escherichia coli strain, MP1, we showed that the SOS response plays a vital role during colonization of the murine gut. In an unperturbed environment, the SOS-off mutant is impaired for stable colonization relative to a wild-type strain, suggesting the presence of genotoxic stress in the mouse gut. We evaluated the possible origins of genotoxic stress in the mouse gut by examining factors associated with the host versus the competing commensal organisms. In a dextran sulfate sodium (DSS) colitis model, the SOS-off colonization defect persisted but was not exacerbated. In contrast, in a germ-free model, the SOS-off mutant colonized with efficiency equal to that seen with the wild-type strain, suggesting that competing commensal organisms might be a significant source of genotoxic stress. This report extends our understanding of the importance of a functional SOS response for bacterial fitness in the context of a complex physiological environment and highlights the SOS response as a possible mechanism that contributes to ongoing genomic changes, including potential antibiotic resistance, in the microbiome of healthy hosts.

New insights into intestinal phages

“…Yet, several pieces of evidence suggest that induction rates are globally higher in the murine GIT than in classical in vitro growth cultures, due to more frequent activation of the DNA damage response (SOS response). 58,62,63 In the case of Lactobacillus reuteri, SOS activation was proposed to result from the activation of specific bacterial metabolic pathways in the GIT. 62 Conflicting results were reported concerning the possible increase or, on the contrary, decrease of E. coli stx prophage induction rates by gut metabolites such as nitric oxide or bile salts (reviewed in ref.…”

The DNA Damage Inducible SOS Response Is a Key Player in the Generation of Bacterial Persister Cells and Population Wide Tolerance

“…Conditions conducive to SOS induction are encountered by E. coli at various host anatomical sites. The SOS response plays a vital role for maintaining colonization of the murine gut by commensal E. coli with competing commensal organisms, a possible source of genotoxic stress (Samuels et al, 2019).…”

Spinal Cord Injury Changes the Structure and Functional Potential of Gut Bacterial and Viral Communities

“…Temperate phages integrate themselves into host genomes and can regulate host gene function (reviewed in reference 134 ) and/or provide their hosts with new functions, like antibiotic resistance, toxin production, and other functions that may promote the virulence of commensals or confer fitness and competitive advantages to the hosts ( 123 , 135 ). However, stressors, like antibiotics, hydrogen peroxide, and changes in nutrients and pH, which activate the bacterial host's SOS response, can induce temperate prophages, causing them to become lytic and ultimately kill host cells ( 123 , 136 , 137 ). Dietary fructose and short-chain fatty acids (SCFAs) were shown to induce Lactobacillus reuteri temperate phages ( 138 ), and bile salts were shown to induce some Salmonella temperate phages ( 139 ).…”