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.
Journal article
2021-01-01T00:00:00+00:00
13
143 - 155
12
SOS response, antimicrobial resistance, drug discovery, Anti-Bacterial Agents, Bacterial Proteins, DNA Repair, Drug Resistance, Bacterial, Enzyme Inhibitors, Exodeoxyribonuclease V, Exodeoxyribonucleases, Gene Expression Regulation, Humans, Molecular Targeted Therapy, Rec A Recombinases, SOS Response, Genetics, Serine Endopeptidases, Signal Transduction, Structure-Activity Relationship, LexA Repressor Protein