Targeting the bacterial SOS response for new antimicrobial agents: drug targets, molecular mechanisms and inhibitors.
Thomas Lanyon-HoggPublished in: Future medicinal chemistry (2021)
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.
Keyphrases
- antimicrobial resistance
- drug resistant
- multidrug resistant
- dna repair
- dna damage
- gram negative
- small molecule
- global health
- acinetobacter baumannii
- oxidative stress
- public health
- klebsiella pneumoniae
- staphylococcus aureus
- protein protein
- emergency department
- anti inflammatory
- dna damage response
- cancer therapy
- pseudomonas aeruginosa
- drug delivery
- adverse drug