Inhibitors of bacterial H2S biogenesis targeting antibiotic resistance and tolerance.
Science
; 372(6547): 1169-1175, 2021 06 11.
Article
in English
| MEDLINE | ID: covidwho-1583231
ABSTRACT
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 γ-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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pseudomonas aeruginosa
/
Staphylococcus aureus
/
Cystathionine gamma-Lyase
/
Enzyme Inhibitors
/
Hydrogen Sulfide
/
Anti-Bacterial Agents
Type of study:
Prognostic study
Language:
English
Journal:
Science
Year:
2021
Document Type:
Article
Affiliation country:
SCIENCE.ABD8377
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