XerC Is Required for the Repair of Antibiotic- and Immune-Mediated DNA Damage in Staphylococcus aureus

To survive in the host environment, pathogenic bacteria need to be able to 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 sensitize 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 the susceptibility of S. aureus to ciprofloxacin. Further characterization 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 defenses. Therefore, the inhibition of XerC may be a viable therapeutic approach to sensitize S. aureus to both antibiotics and the immune response. To survive in the host environment, pathogenic bacteria need to be able to 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 sensitize bacteria to antibiotics and the immune response.

Automated summary

Pathogenic bacteria need to repair DNA damage from antibiotics and the immune system to survive in the host environment. The SOS response is a vital pathway for bacterial DNA repair and could be targeted for new therapeutics to sensitize bacteria to antibiotics and the immune response. Through a mutant screen, 16 genes potentially involved in the SOS response were identified in Staphylococcus aureus, with 3 genes affecting susceptibility to ciprofloxacin. The loss of the tyrosine recombinase XerC also increased susceptibility to antibiotics and host immune defenses, suggesting that inhibiting XerC could sensitize S. aureus to both antibiotics and the immune response.