Role of Mycobacterium tuberculosis expressing unique protein Rv000B in immune modulation of host cell machinery

Abstract

Abstract Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb.), an intracellular pathogen remains a major global health problem. M.tb., comprising more than 120 species has evolved by successive genomic reduction events. Comparative genomic and proteomic analysis of 13 Mycobacterium species classified into Strict pathogens (virulent), Opportunistic pathogens (Non-tuberculous Mycobacteria, NTM) and the Non-pathogenic bacteria revealed the presence of 25 unique protein. These 25 proteins share less than 20% homology with any other proteins of Mycobacteria species used in the study. Rv000B, one of the unique proteins is present in M.tb and M. bovis BCG only. The presence of Rv000B in M. tb and M.bovis BCG only points to its importance as “Signature proteins”, suggesting that Rv000B could be used for its diagnostic potential. Rv000B is a hypothetical protein and hence it will be interesting to study their functional role in the pathogenesis of M.tb. In-silico analysis of Rv000B revealed that this protein is highly disordered and unstable. Immunogenicity of Rv000B protein was evaluated by treating the splenocytes ex-vivo obtained from mice that were previously immunized with Rv000B protein. Our results showed that Rv000B is highly antigenic and elicited a pro-inflammatory immune response. High IgG reactivity of Rv000B is also seen in immunized mice and different categories of TB patients. Besides inducing Th1 responses, it also significantly induced apoptosis of macrophages. Therefore, these pro-host antigenic proteins are ideal candidates to produce recombinant BCG vaccine to enhances its vaccine potential.