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

Sachin K. Samuchiwal, Sultan Tousif, Dhiraj K. Singh, Arun Kumar, Anamika Ghosh, Kuhulika Bhalla, Prem Prakash, Sushil Kumar, Maitree Bhattacharyya, Prashini Moodley, Gobardhan Das, Anand Ranganathan

Research output: Contribution to journalArticle

9 Scopus citations

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-6:CFP10 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-6:CFP10 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-6:CFP10 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-6:CFP10 association could, therefore, be an alternate method for attenuating M. tuberculosis, and a possible route towards future vaccine generation.

Original languageEnglish (US)
Article number355
JournalBMC Infectious Diseases
Volume14
Issue number1
DOIs
StatePublished - Jul 25 2014

Keywords

  • CFP10
  • ESAT-6
  • Human COX3
  • Protein-protein interactions
  • Th1
  • Th17
  • Tuberculosis

ASJC Scopus subject areas

  • Infectious Diseases

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