Proteomic analysis of streptomycin resistant and sensitive clinical isolates of Mycobacterium tuberculosis

Two-dimensional gel electrophoresis (2DE) and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry was employed for analyzing the protein profiles. Homology and in silico characterization for identified proteins was assessed using BLAST, InterProScan and KEGG database searches. Computational studies on the possible interactions between SM and identified proteins were carried out by a battery of online servers and softwares, namely, CLUSTALW (KEGG), I-TASSER, VMD, PatchDock and FireDock. On comparing 2DE patterns, nine proteins were found consistently overexpressed in SM resistant isolates and were identified as Rv0350, Rv0440, Rv1240, Rv3075c, Rv2971, Rv3028c, Rv2145c, Rv2031c and Rv0569. In silico docking analysis showed significant interactions of SM with essential (Rv0350, Rv0440 and Rv2971) and non essential (Rv1240, Rv3075c and Rv2031c) genes.The computational results suggest high protein binding affinity of SM and suggested many possible interactions between identified proteins and the drug. Bioinformatic analysis proves attributive for analysis of diversity of proteins identified by whole proteome analysis. In-depth study of the these proteins will give an insight into probable sites of drug action other than established primary sites and hence may help in search of novel chemotherapeutic agents at these new sites as inhibitors.Tuberculosis is one of the most challenging infectious diseases. Globally, 9.2 million new cases and 1.7 million deaths occur due to this disease [1]. Its impact on public health is further aggravated by co-infection with human immunodeficiency virus, emergence of multi-drug resistant strains and reactivation of the dormant bacteria. Attempt for primary prevention using Bacillus Calmette Guerin (BCG) and other integral vaccines have generally been disappointing though some subunit vaccines are under trial [2]. The excessive emergence of drug resistant tuberculosis has stimulated interest in the under