In silico identification and characterization of a hypothetical protein of Mycobacterium tuberculosis EAI5 as a potential virulent factor

Tuberculosis, a life threatening disease caused by different strains of Mycobacterium tuberculosis is creating an alarming condition due to the emergence of increasing multi drug resistance (MDR) trait. In this study, in silico approach was used for the identification of a conserved novel virulent factor in Mycobacterium tuberculosis EAI5 (Accession no.CP006578) which can also act as potential therapeutic target. Systematic comparative search of genes that are common to strain EAI5 and other human pathogenic strains of M. tuberculosis enlisted 408 genes. These were absent in the non-pathogenic Mycobacterium smegmatis MC2155 and in the human genome. Among those genes, only the protein coding hypothetical genes (97 out of 408) and their corresponding products were selected for further exploration. Of these, 11 proteins were found to have notable conserved domains, of which one hypothetical protein (NCBI Acc No. AGQ35418.1) was selected for further in silico exploration which was found to have two functional domains, one having phosphatidylinositol specific phospholipase C (PI-PLC) activity while the other short domain with weak lectin binding activity. As PI-PLC contributes virulence property in some pathogenic bacteria with a broad range of activities, different bioinformatic tools were used to explore its physicochemical and other important properties which indicated its secretary nature. This PI-PLC was previously not reported as drug/vaccine target to the best of our knowledge. Its predicted 3D structure can be explored for development of inhibitor for novel therapeutic strategies against MDR-TB.