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Research Studies is a monthly compilation of research articles funded by AHRQ or authored by AHRQ researchers and recently published in journals or newsletters.
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Edwards RL, Heueck I, Lee SG
Potent, specific MEPicides for treatment of zoonotic staphylococci.
In this study, researchers demonstrated that fosmidomycin (FSM) inhibited the first step of the isoprenoid biosynthetic pathway catalyzed by deoxyxylulose phosphate reductoisomerase (DXR) in staphylococci. They synthesized a series of lipophilic ester prodrugs (termed MEPicides) structurally related to FSM, and their data indicated that the presence of the prodrug moiety not only substantially increased potency of the inhibitors against staphylococci but also bypassed the need for GlpT-mediated cellular transport. They concluded that their data indicated that the prodrug MEPicides selectively and robustly inhibited DXR in zoonotic staphylococci, and, further, that DXR represented a promising, druggable target for future development.
AHRQ-funded; HS021736; HS024269.
Citation: Edwards RL, Heueck I, Lee SG . Potent, specific MEPicides for treatment of zoonotic staphylococci. PLoS Pathog 2020 Jun;16(6):e1007806. doi: 10.1371/journal.ppat.1007806..
Keywords: Infectious Diseases, Antibiotics, Medication, Genetics