The contribution of DNA repair pathways to Staphylococcus aureus fitness and fidelity during nitric oxide stress

Abstract

Staphylococcus aureus is a major human pathogen that causes a variety of illnesses, ranging from minor skin and soft tissue infections to more severe systemic infections. Although the primary host immune response can typically clear bacterial infections, S. aureus is uniquely resistant to inflammation. For instance, our laboratory has determined that S. aureus is highly resistant to nitric oxide (NO.), an important component of the innate immune response that plays a role in both immunomodulatory and antibacterial processes. Additionally, NO. and its derivatives can cause damage to S. aureus DNA, more specifically, deamination and/or oxidation of DNA bases; however, regulation and repair mechanisms of DNA in S. aureus are understudied. Thus, we hypothesize that several DNA repair mechanisms may account for the replication fidelity of S. aureus and may contribute to fitness in the presence of NO. Here, we show the role of several DNA repair mechanisms in S. aureus. More specifically, we found that recombinational repair genes recJ, recG, and polA may play a role in the repair of NO.-induced replication fork collapses. We also show the role of the base excision repair pathway protein, MutY, in reducing NO.-mediated mutagenesis. Overall, our results suggest that NO. leads to DNA damage, which subsequently induces the activity of several DNA repair pathways, contributing to the replication fidelity and fitness of S. aureus.