title: Comparative Proteomic Analyses of Avirulent, Virulent, and Clinical Strains of Mycobacterium tuberculosis Identify Strain-specific Patterns.
abstract: Mycobacterium tuberculosis is an adaptable intracellular pathogen, existing in both dormant as well as active disease-causing states. Here, we report systematic proteomic analyses of four strains, H37Ra, H37Rv, and clinical isolates BND and JAL, to determine the differences in protein expression patterns that contribute to their virulence and drug resistance. Resolution of lysates of the four strains by liquid chromatography, coupled to mass spectrometry analysis, identified a total of 2161 protein groups covering ∼54% of the predicted M. tuberculosis proteome. Label-free quantification analysis of the data revealed 257 differentially expressed protein groups. The differentially expressed protein groups could be classified into seven K-means cluster bins, which broadly delineated strain-specific variations. Analysis of the data for possible mechanisms responsible for drug resistance phenotype of JAL suggested that it could be due to a combination of overexpression of proteins implicated in drug resistance and the other factors. Expression pattern analyses of transcription factors and their downstream targets demonstrated substantial differential modulation in JAL, suggesting a complex regulatory mechanism. Results showed distinct variations in the protein expression patterns of Esx and mce1 operon proteins in JAL and BND strains, respectively. Abrogating higher levels of ESAT6, an important Esx protein known to be critical for virulence, in the JAL strain diminished its virulence, although it had marginal impact on the other strains. Taken together, this study reveals that strain-specific variations in protein expression patterns have a meaningful impact on the biology of the pathogen.
authors.affiliation: National Institute of Immunology, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067.
authors.forename: Gagan Deep
authors.initials: GD
authors.lastname: Jhingan
authors.affiliation: National Institute of Immunology, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Kumari
authors.affiliation: Drug Discovery Research Center, Translational Health Science and Technology Institute, Faridabad, Haryana 121004.
authors.forename: Shilpa V
authors.initials: SV
authors.lastname: Jamwal
authors.affiliation: Cellular Immunology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067.
authors.forename: Haroon
authors.initials: H
authors.lastname: Kalam
authors.affiliation: National Institute of Immunology, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067.
authors.forename: Divya
authors.initials: D
authors.lastname: Arora
authors.affiliation: Cellular Immunology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067.
authors.forename: Neharika
authors.initials: N
authors.lastname: Jain
authors.affiliation: Institute of Mathematical Sciences, Chennai 600113, India.
authors.forename: Lakshmi Krishna
authors.initials: LK
authors.lastname: Kumaar
authors.affiliation: Institute of Mathematical Sciences, Chennai 600113, India.
authors.forename: Areejit
authors.initials: A
authors.lastname: Samal
authors.affiliation: Cellular Immunology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067.
authors.forename: Kanury V S
authors.initials: KVS
authors.lastname: Rao
authors.affiliation: Cellular Immunology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067.
authors.forename: Dhiraj
authors.initials: D
authors.lastname: Kumar
authors.affiliation: National Institute of Immunology, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067. Electronic address: vinaykn@nii.ac.in.
authors.forename: Vinay Kumar
authors.initials: VK
authors.lastname: Nandicoori
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity; D040901:Proteomics; D013045:Species Specificity; D014774:Virulence
chemical_list: D001426:Bacterial Proteins
keywords: Mycobacterium tuberculosis; mycobacteria; protein expression; proteomics; virulence factor