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

作者：Samuchiwal Sachin Kumar; Tousif Sultan; Singh Dhiraj Kumar; Kumar Arun; Ghosh Anamika; Bhalla Kuhulika; Prakash Prem; Kumar Sushil; Bhattacharyya Maitree; Moodley Prashini; Das Gobardhan^*; Ranganathan Anand

来源：BMC Infectious Diseases, 2014, 14(1): 355.

DOI：10.1186/1471-2334-14-355

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

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. %26lt;br%26gt;Methods: We therefore sought to improvise a method to attenuate M. tuberculosis while retaining the latter%26apos;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. %26lt;br%26gt;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. %26lt;br%26gt;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.

• 出版日期2014-7-1