Dysregulation of bacterial proteolytic machinery by a new class of antibiotics.
Nat Med
; 11(10): 1082-7, 2005 Oct.
Article
em En
| MEDLINE
| ID: mdl-16200071
ABSTRACT
Here we show that a new class of antibiotics-acyldepsipeptides-has antibacterial activity against Gram-positive bacteria in vitro and in several rodent models of bacterial infection. The acyldepsipeptides are active against isolates that are resistant to antibiotics in clinical application, implying a new target, which we identify as ClpP, the core unit of a major bacterial protease complex. ClpP is usually tightly regulated and strictly requires a member of the family of Clp-ATPases and often further accessory proteins for proteolytic activation. Binding of acyldepsipeptides to ClpP eliminates these safeguards. The acyldepsipeptide-activated ClpP core is capable of proteolytic degradation in the absence of the regulatory Clp-ATPases. Such uncontrolled proteolysis leads to inhibition of bacterial cell division and eventually cell death.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bactérias
/
Proteínas de Escherichia coli
/
Depsipeptídeos
/
Endopeptidase Clp
/
Antibacterianos
Limite:
Animals
Idioma:
En
Revista:
Nat Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
MEDICINA
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Alemanha