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

Future Med Chem

Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK.

Published: January 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.

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http://dx.doi.org/10.4155/fmc-2020-0310DOI Listing

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