XerC is required for the repair of antibiotic- and immune-mediated DNA damage in Staphylococcus aureus

Abstract

To survive in the host environment, pathogenic bacteria need to be able repair DNA damage caused by both antibiotics and the immune system. The SOS response is a key bacterial pathway to repair DNA double strand breaks and may therefore be a good target for novel therapeutics to sensitise bacteria to antibiotics and the immune response. However, the genes required for the SOS response in Staphylococcus aureus have not been fully established. Therefore, we carried out a screen of mutants involved in various DNA repair pathways to understand which were required for induction of the SOS response. This led to the identification of 16 genes that may play a role in SOS response induction, and of these, 3 that affected susceptibility of S. aureus to ciprofloxacin. Further characterisation revealed that, in addition to ciprofloxacin, loss of the tyrosine recombinase XerC increased the susceptibility of S. aureus to various classes of antibiotics, as well as to host immune defences. Therefore, the inhibition of XerC may be a viable therapeutic approach to sensitise S. aureus to both antibiotics and the immune response.