Inhibitors of bacterial H2S biogenesis targeting antibiotic resistance and tolerance.
Science
; 372(6547): 1169-1175, 2021 06 11.
Artículo
en Inglés
| 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.
Texto completo:
Disponible
Colección:
Bases de datos internacionales
Base de datos:
MEDLINE
Asunto principal:
Pseudomonas aeruginosa
/
Staphylococcus aureus
/
Cistationina gamma-Liasa
/
Inhibidores Enzimáticos
/
Sulfuro de Hidrógeno
/
Antibacterianos
Tipo de estudio:
Estudio pronóstico
Idioma:
Inglés
Revista:
Science
Año:
2021
Tipo del documento:
Artículo
País de afiliación:
SCIENCE.ABD8377
Similares
MEDLINE
...
LILACS
LIS