A peptide fragment from the human COX3 protein disrupts association of Mycobacterium tuberculosis virulence proteins ESAT-6 and CFP10, inhibits mycobacterial growth and mounts protective immune response.
BMC Infect Dis
; 14: 355, 2014 Jul 01.
Article
en En
| MEDLINE
| ID: mdl-24985537
ABSTRACT
BACKGROUND:
Tuberculosis (TB) is one of the most prevalent infectious diseases affecting millions worldwide. The currently available anti-TB drugs and vaccines have proved insufficient to contain this scourge, necessitating an urgent need for identification of novel drug targets and therapeutic strategies. The disruption of crucial protein-protein interactions, especially those that are responsible for virulence in Mycobacterium tuberculosis - for example the ESAT-6CFP10 complex - are a worthy pursuit in this direction.METHODS:
We therefore sought to improvise a method to attenuate M. tuberculosis while retaining the latter's antigenic properties. We screened peptide libraries for potent ESAT-6 binders capable of dissociating CFP10 from ESAT-6. We assessed the disruption by a peptide named HCL2, of the ESAT-6CFP10 complex and studied its effects on mycobacterial survival and virulence.RESULTS:
We found that HCL2, derived from the human cytochrome c oxidase subunit 3 (COX3) protein, disrupts ESAT-6CFP10 complex, binds ESAT-6 potently, disintegrates bacterial cell wall and inhibits extracellular as well as intracellular mycobacterial growth. In addition, an HCL2 expressing M. tuberculosis strain induces both Th1 and Th17 host protective responses.CONCLUSIONS:
Disruption of ESAT-6CFP10 association could, therefore, be an alternate method for attenuating M. tuberculosis, and a possible route towards future vaccine generation.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteínas Bacterianas
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Tuberculosis Pulmonar
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Mycobacterium tuberculosis
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Antígenos Bacterianos
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
BMC Infect Dis
Asunto de la revista:
DOENCAS TRANSMISSIVEIS
Año:
2014
Tipo del documento:
Article