Targeting the bacterial SOS response for new antimicrobial agents: drug targets, molecular mechanisms and inhibitors

Antimicrobial resistance is a pressing threat to global health, with multidrug-resistant pathogens becoming increasingly prevalent. The bacterial SOS pathway functions in response to DNA damage that occurs during infection, initiating several pro-survival and resistance mechanisms, such as DNA repair and hypermutation. This makes SOS pathway components potential targets that may combat drug-resistant pathogens and decrease resistance emergence. This review discusses the mechanism of the SOS pathway; the structure and function of potential targets AddAB, RecBCD, RecA and LexA; and efforts to develop selective small-molecule inhibitors of these proteins. These inhibitors may serve as valuable tools for target validation and provide the foundations for desperately needed novel antibacterial therapeutics.

Automated summary

The review explores the role of the bacterial SOS pathway in combating drug-resistant pathogens, potential targets for inhibition such as AddAB, RecBCD, RecA, and LexA, and efforts to develop selective small-molecule inhibitors. These inhibitors may serve as valuable tools for combating drug resistance and developing novel antibacterial therapeutics.