Inhibitors of bacterial H2S biogenesis targeting antibiotic resistance and tolerance.
Science
; 372(6547): 1169-1175, 2021 06 11.
Article
em En
| MEDLINE
| ID: mdl-34112687
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pseudomonas aeruginosa
/
Staphylococcus aureus
/
Cistationina gama-Liase
/
Inibidores Enzimáticos
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Sulfeto de Hidrogênio
/
Antibacterianos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Science
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos