Abrogation of SOS mutagenesis by the E. coli OxyR oxidative stress response

ABSTRACT Most bacteria are capable of living and surviving under a wide range of conditions, including exposures to chemical and physical stressors. A key to survival under adverse conditions is their ability to induce specific stress response systems that mitigate harmful effects. Examples are the well-studied SOS system induced under replication stress caused by DNA damage and the OxyR response induced by oxidative stress (e.g., hydroxyl radicals). In the present study, we have investigated interactions between these two systems under the assumption that harmful conditions may generally induce more than one bacterial response, and in such a case, their combined effect might feature additional factors critical for survival. We used Escherichia coli strains that were constitutively induced for the SOS system (using the recA730 allele) in combination with the OxyR oxidative response (using the oxyR2 c allele). The main finding was that joint expression of these systems strongly diminished the mutator effect associated with SOS induction. This so called SOS mutator effect is due to the error-prone DNA polymerase Pol V (product of the umuDC operon, UmuD′ 2 UmuC), which is derepressed upon SOS induction. Gene expression studies revealed an overall reduction of genes of the SOS regulon in the double mutant, with the largest reduction for the genes of the umuDC operon. In parallel, Western blots showed the UmuD and UmuD′ proteins to be severely depleted from extracts of such strains. The data suggest an additional layer of control of SOS mutagenesis under certain stress conditions. IMPORTANCE Many microorganisms such as pathogenic bacteria that attempt to invade a host will encounter a series of host-produced challenges that try to thwart their entry into and establishment within the host. As a countermeasure, the invading organisms have evolutionarily developed a range of stress responses that will help them to counter such challenges. The current study explores what happens in the bacterium E. coli when two such systems are induced simultaneously. We show that, remarkably, the strong increase in the mutation rate upon SOS induction (provoked by DNA replication stress) is nearly completely abolished by OxyR oxidative stress response. This study may serve as a paradigm for studies that might reveal novel regulatory features in cells subjected to multiple stressors.