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Publication Abstract from PubMed

Emergent resistance to all clinical antibiotics calls for the next generation of therapeutics. Here we report an effective antimicrobial strategy targeting the bacterial hydrogen sulfide (H2S)-mediated defense system. We identified cystathionine gamma-lyase (CSE) as the primary generator of H2S in two major human pathogens, Staphylococcus aureus and Pseudomonas aeruginosa, and discovered small molecules that inhibit bacterial CSE. These inhibitors potentiate bactericidal antibiotics against both pathogens in vitro and in mouse models of infection. CSE inhibitors also suppress bacterial tolerance, disrupting biofilm formation and substantially reducing the number of persister bacteria that survive antibiotic treatment. Our results establish bacterial H2S as a multifunctional defense factor and CSE as a drug target for versatile antibiotic enhancers.

Inhibitors of bacterial H2S biogenesis targeting antibiotic resistance and tolerance.,Shatalin K, Nuthanakanti A, Kaushik A, Shishov D, Peselis A, Shamovsky I, Pani B, Lechpammer M, Vasilyev N, Shatalina E, Rebatchouk D, Mironov A, Fedichev P, Serganov A, Nudler E Science. 2021 Jun 11;372(6547):1169-1175. doi: 10.1126/science.abd8377. PMID:34112687^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.