title: 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.
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.
authors.forename: Sachin Kumar
authors.initials: SK
authors.lastname: Samuchiwal
authors.forename: Sultan
authors.initials: S
authors.lastname: Tousif
authors.forename: Dhiraj Kumar
authors.initials: DK
authors.lastname: Singh
authors.forename: Arun
authors.initials: A
authors.lastname: Kumar
authors.forename: Anamika
authors.initials: A
authors.lastname: Ghosh
authors.forename: Kuhulika
authors.initials: K
authors.lastname: Bhalla
authors.forename: Prem
authors.initials: P
authors.lastname: Prakash
authors.forename: Sushil
authors.initials: S
authors.lastname: Kumar
authors.forename: Maitree
authors.initials: M
authors.lastname: Bhattacharyya
authors.forename: Prashini
authors.initials: P
authors.lastname: Moodley
authors.affiliation: Recombinant Gene Products Group, International Centre for Genetic Engineering and Biotechnology, ICGEB, Aruna Asaf Ali Marg, New Delhi 110067, India. gobardhan.das07@gmail.com.
authors.forename: Gobardhan
authors.initials: G
authors.lastname: Das
authors.forename: Anand
authors.initials: A
authors.lastname: Ranganathan
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D010446:Peptide Fragments / Q000494:pharmacology; D014397:Tuberculosis, Pulmonary / Q000382:microbiology*; D014774:Virulence
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D010446:Peptide Fragments