Heterocyclic Diaryliodonium-Based Inhibitors of Carbapenem-Resistant Acinetobacter baumannii.

ABSTRACT: Finding new therapeutic strategies against Gram-negative pathogens such as Acinetobacter baumannii is challenging. Starting from diphenyleneiodonium (dPI) salts, which are moderate Gram-positive antibacterials, we synthesized a focused heterocyclic library and found a potent inhibitor of patient-derived multidrug-resistant Acinetobacter baumannii strains that significantly reduced bacterial burden in an animal model of infection caused by carbapenem-resistant Acinetobacter baumannii (CRAB), listed as a priority 1 critical pathogen by the World Health Organization. Next, using advanced chemoproteomics platforms and activity-based protein profiling (ABPP), we identified and biochemically validated betaine aldehyde dehydrogenase (BetB), an enzyme that is involved in the metabolism and mainten

SUBMITTER: Kumari P 

PROVIDER: S-EPMC10101131 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature