Real-Time Biosynthetic Reaction Monitoring Informs the Mechanism of Action of Antibiotics.

ABSTRACT: The rapid spread of drug-resistant pathogens and the declining discovery of new antibiotics have created a global health crisis and heightened interest in the search for novel antibiotics. Beyond their discovery, elucidating mechanisms of action has necessitated new approaches, especially for antibiotics that interact with lipidic substrates and membrane proteins. Here, we develop a methodology for real-time reaction monitoring of the activities of two bacterial membrane phosphatases, UppP and PgpB. We then show how we can inhibit their activities using existing and newly discovered antibiotics such as bacitracin and teixobactin. Additionally, we found that the UppP dimer is stabilized by phosphatidylethanolamine, which, unexpectedly, enhanced the speed of substrate processing. Overall, ou

SUBMITTER: Oluwole AO 

PROVIDER: S-EPMC10941186 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature