A new antibiotic with potent activity targets MscL.
J Antibiot (Tokyo)
; 68(7): 453-62, 2015 Jul.
Article
en En
| MEDLINE
| ID: mdl-25649856
ABSTRACT
The growing problem of antibiotic-resistant bacteria is a major threat to human health. Paradoxically, new antibiotic discovery is declining, with most of the recently approved antibiotics corresponding to new uses for old antibiotics or structurally similar derivatives of known antibiotics. We used an in silico approach to design a new class of nontoxic antimicrobials for the bacteria-specific mechanosensitive ion channel of large conductance, MscL. One antimicrobial of this class, compound 10, is effective against methicillin-resistant Staphylococcus aureus with no cytotoxicity in human cell lines at the therapeutic concentrations. As predicted from in silico modeling, we show that the mechanism of action of compound 10 is at least partly dependent on interactions with MscL. Moreover we show that compound 10 cured a methicillin-resistant S. aureus infection in the model nematode Caenorhabditis elegans. Our work shows that compound 10, and other drugs that target MscL, are potentially important therapeutics against antibiotic-resistant bacterial infections.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Mecanotransducción Celular
/
Inhibidores Enzimáticos
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Staphylococcus aureus Resistente a Meticilina
/
Canales Iónicos
/
Antibacterianos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Antibiot (Tokyo)
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos