Comparative Proteomic Analysis of Aminoglycosides Resistant and Susceptible Mycobacterium tuberculosis Clinical Isolates for Exploring Potential Drug TargetsReport as inadecuate




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Aminoglycosides, amikacin AK and kanamycin KM are second line anti-tuberculosis drugs used to treat tuberculosis TB and resistance to them affects the treatment. Membrane and membrane associated proteins have an anticipated role in biological processes and pathogenesis and are potential targets for the development of new diagnostics-vaccine-therapeutics. In this study we compared membrane and membrane associated proteins of AK and KM resistant and susceptible Mycobacterium tuberculosis isolates by 2DE coupled with MALDI-TOF-TOF-MS and bioinformatic tools. Twelve proteins were found to have increased intensities PDQuest Advanced Software in resistant isolates and were identified as ATP synthase subunit alpha Rv1308, Trigger factor Rv2462c, Dihydrolipoyl dehydrogenase Rv0462, Elongation factor Tu Rv0685, Transcriptional regulator MoxR1Rv1479, Universal stress protein Rv2005c, 35kDa hypothetical protein Rv2744c, Proteasome subunit alpha Rv2109c, Putative short-chain type dehydrogenase-reductase Rv0148, Bacterioferritin Rv1876, Ferritin Rv3841 and Alpha-crystallin-HspX Rv2031c. Among these Rv2005c, Rv2744c and Rv0148 are proteins with unknown functions. Docking showed that both drugs bind to the conserved domain Usp, PspA and SDR domain of these hypothetical proteins and GPS-PUP predicted potential pupylation sites within them. Increased intensities of these proteins and proteasome subunit alpha might not only be neutralized-modulated the drug molecules but also involved in protein turnover to overcome the AK and KM resistance. Besides that Rv1876, Rv3841 and Rv0685 were found to be associated with iron regulation signifying the role of iron in resistance. Further research is needed to explore how these potential protein targets contribute to resistance of AK and KM.



Author: Divakar Sharma, Bhavnesh Kumar, Manju Lata, Beenu Joshi, Krishnamurthy Venkatesan, Sangeeta Shukla, Deepa Bisht

Source: http://plos.srce.hr/



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