A γ-Lactam Siderophore Antibiotic Effective against Multidrug-Resistant Gram-Negative Bacilli Article Swipe

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Siderophore Microbiology Bacilli Antibiotics Lactam Multiple drug resistance Gram-negative bacterial infections Gram Gram-negative bacteria Biology Bacteria Chemistry Genetics Escherichia coli Stereochemistry Gene

Goldberg J.A. , Hoan Nguyen , Vijay Kumar , Spencer E.J. , Daniël Hoyer , Marshall E.K. , Anna Cmolik , Margaret O’Shea , Marshall S.H. , Hujer A.M. , Hujer K.M. , Rudin S.D. , Domitrovic T.N. , Bethel C.R. , Papp-Wallace K.M. , Logan L.K. , Federico Pérez , Jacobs M.R. , van Duin D. , Kreiswirth B.M. , Bonomo R.A. , Plummer M.S. , van den Akker F. ·

YOU? · · 2024 · Open Access · · DOI: https://doi.org/10.17615/6a2r-nh24 · OA: W4400022330

Treatment of multidrug-resistant Gram-negative bacterial pathogens represents a critical clinical need. Here, we report a novel γ-lactam pyrazolidinone that targets penicillin-binding proteins (PBPs) and incorporates a siderophore moiety to facilitate uptake into the periplasm. The MIC values of γ-lactam YU253434, 1, are reported along with the finding that 1 is resistant to hydrolysis by all four classes of β-lactamases. The druglike characteristics and mouse PK data are described along with the X-ray crystal structure of 1 binding to its target PBP3.