Secretory Proteome Analysis of Streptomycin-Resistant Mycobacterium tuberculosis Clinical Isolates.
Tuberculosis still remains one of the most fatal infectious diseases. Streptomycin (SM) is the drug of choice, especially for patients with multidrug-resistant tuberculosis or category II patients, because it targets the protein synthesis machinery by interacting with steps of translation. Several mechanisms have been proposed to explain the resistance, but our knowledge is inadequate. Secretome often plays an important role in pathogenesis and is considered an attractive reservoir for the development of novel diagnostic markers and targets. In this study, we analyze the secretory proteins of streptomycin-resistant Mycobacterium tuberculosis isolates by 2-dimensional gel electrophoresis-matrix assisted laser desorption/ionization-time-of-flight mass spectrometry and bioinformatic tools. Fifteen overexpressed proteins were identified in a resistant isolate that belonged to various categories such as virulence/detoxification/adaptation, intermediary metabolism and respiration, and conserved hypotheticals. Among them, Rv1860, Rv1980c, Rv2140c, Rv1636, and Rv1926c were proteins of an undefined role. Molecular docking of these proteins with SM showed that it binds to their conserved domains and suggests that these might neutralize/compensate the effect of the drug. The interactome also suggests that overexpressed proteins along with their interactive partner might be involved in M. tuberculosis virulence and resistance. The cumulative effect of these overexpressed proteins could involve SM resistance, and these might be used as diagnostic markers or potential drug targets.
1 Department of Biochemistry, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra, India.
Divakar
D
Sharma
1 Department of Biochemistry, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra, India.
Deepa
D
Bisht
D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D062105:Molecular Docking Simulation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000378:metabolism; D025941:Protein Interaction Mapping; D020543:Proteome / Q000378:metabolism*; D013307:Streptomycin / Q000494:pharmacology*
D001426:Bacterial Proteins; D020543:Proteome; D013307:Streptomycin
2DE; MALDI-TOF/MS; Mycobacterium tuberculosis; bioinformatic tools; secretory proteome; streptomycin