Inhibition of the SOS response by olivetol improves the efficacy of DNA-damaging antibiotics in Escherichia coli

It is known that the rapid increase in antibiotic-resistant bacteria is reducing the effectiveness of existing antibiotics. The spread of resistant Escherichia coli strains has become a major concern in public health. Developing compounds that increase antibiotic activity is a promising alternative strategy to overcome this problem. SOS response mechanism in bacteria activates DNA repair and increases antibiotic resistance. Natural sources, such as lichens, are valuable for discovering potential SOS inhibitors due to their unique secondary metabolites with medicinal potential. This study aims to enhance the efficacy of antibiotics in E. coli by inhibiting SOS with olivetol, a natural metabolite derived from lichens. The SOS inhibition potential of olivetol was quantitatively assessed using qRT-PCR and GFP-based monitor strains. Moreover, MIC values of DNA damage-inducing ciprofloxacin, trimethoprim, nitrofurantoin and mitomycin C antibiotics were reassessed following combined treatment with olivetol. Overall, the results show that olivetol effectively suppresses the SOS response at high concentrations and reduces the MIC values of the antibiotics trimethoprim, nitrofurantoin, and mitomycin C. These findings indicate that olivetol has significant potential as a natural SOS inhibitor that can enhance the performances of certain antibiotics.