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Discovery and validation of broadly effective LpxH inhibitors as novel therapeutics against multi-drug resistant Gram-negative pathogens

Objective

Project Summary/AbstractAn alarming number of Gram-negative nosocomial pathogens have acquired resistance to nearly all currentlyavailable antibiotics, making it very difficult to treat patients effectively. Moreover, in the last decade, only ahandful of new antimicrobial agents have been introduced, and these have mostly targeted drug-resistantGram-positive pathogens such as methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci(VRE). The goal of this proposal is to develop a high-throughput screening assay to discover and validate smallmolecule inhibitors of LpxH, an essential enzyme in the lipid A biosynthetic pathway, as novel antibiotics for thetreatment of infections caused by multidrug-resistant Gram-negative pathogens.

Investigators
Zhou, Pei
Institution
Duke University
Start date
2019
End date
2023
Project number
1R01AI139216-01A1
Accession number
139216