Antimicrobial Resistance and SOS-Mediated DNA Damage Responses: Molecular Mechanisms and Emerging Therapeutic Targets

Antibiotic exposure promotes the emergence of antimicrobial resistance by activating SOS-dependent mutagenesis and facilitating horizontal gene transfer (HGT), both of which accelerate bacterial adaptation under selective pressure. Consequently, pharmacological inhibition of the SOS response has emerged as a promising strategy to suppress resistance evolution and enhance the efficacy of existing antibiotics. In particular, proteins involved in homologous recombination and DNA repair, such as RecA and LexA, represent attractive therapeutic targets for preventing SOS activation and limiting mutagenesis. This review highlights the pivotal role of the bacterial SOS response in antimicrobial resistance and discusses emerging strategies to therapeutically target the SOS pathway for combating resistant pathogens.