Mycobacterium tuberculosis effectors involved in host–pathogen interaction revealed by a multiple scales integrative pipeline

Mycobacterium tuberculosis (Mtb) has evolved multiple strategies to counter host immunity. Proteins are one important player in the host–pathogen interaction. A comprehensive list of such proteins will benefit our understanding of pathogenesis of Mtb. A genome-scale dataset was created from different sources of published data: global gene expression studies in disease models; genome-wide insertional mutagenesis defining gene essentiality under different conditions; genes lost in clinical isolates; subcellular localization analysis and non-homology analysis. Using data mining and meta-analysis, expressed proteins critical for intracellular survival of Mtb are first identified, followed by subcellular localization analysis, finally filtering a series of subtractive channel of analysis to find out promising drug target candidates. The analysis found 54 potential candidates essential for the intracellular survival of the pathogen and non-homologous to host or gut flora, and might be promising drug targets. Based on our meta-analysis and bioinformatics analysis, 54 hits were found from Mtb around 4000 open reading frames. These hits can be good candidates for further experimental investigation.