Small molecule inhibitor of FosA expands fosfomycin activity to multidrug-resistant Gram-negative pathogens.

In this study, we describe the discovery and biochemical and structural characterization of 3-bromo-6-[3-(3-bromo-2-oxo-1H-pyrazolo[1,5-a]pyrimidin-6-yl)-4-nitro-1H-pyrazol-5-yl]-1H-pyrazolo[1,5-a]pyrimidin-2-one (ANY1), a small molecule active site inhibitor of FosA. Importantly, ANY1 potentiates FOM activity in representative Gram-negative pathogens. Collectively, our study outlines a new strategy to expand FOM activity to a broader spectrum of Gram-negative pathogens, including multidrug-resistant strains. PMID: 30642934 [PubMed - as supplied by publisher]

https://www.ncbi.nlm.nih.gov/pubmed/30642934?dopt=Abstract

Source: Antimicrobial Agents and Chemotherapy - January 14, 2019 Category: Microbiology Authors: Tomich AD, Klontz EH, Deredge D, Barnard JP, McElheny CL, Eshbach ML, Weisz OA, Wintrode P, Doi Y, Sundberg EJ, Sluis-Cremer N Tags: Antimicrob Agents Chemother Source Type: research