Title:Proteome Analysis of Ofloxacin and Moxifloxacin Induced Mycobacterium tuberculosis Isolates by Proteomic Approach
Volume: 22
Issue: 4
Author(s): Manju Lata, Divakar Sharma, Bhavnesh kumar, Nirmala Deo, Pramod Kumar Tiwari, Deepa Bisht and Krishnamurthy Venkatesan
Affiliation:
Keywords:
Bioinformatic tools, drug induced, mass spectrometry, moxifloxacin, Mycobacterium tuberculosis, ofloxacin.
Abstract: Ofloxacin (OFX) and moxifloxacin (MOX) are the most promising second line drugs for
tuberculosis treatment. Although the primary mechanism of action of OFX and MOX is gyrase inhibition,
other possible mechanisms cannot be ruled out. Being the functional moiety of cell, the proteins
act as primary targets for developing drugs, diagnostics and therapeutics. In this study we have investigated
the proteomic changes of Mycobacterium tuberculosis isolates induced by OFX and MOX by
applying comparative proteomic approaches based on two-dinensional gel electrophoresis (2DE)
along with matrix assisted laser desorption ionisation time of flight mass spectrometry (MALDI
TOF/TOF-MS) and bioinformatic tools. The findings are likely to provide new understanding of OFX and MOX mechanisms
that might be helpful in exploring new diagnostics and drug targets. Our study explored eleven proteins (Rv2889c,
Rv2623, Rv0952, Rv1827, Rv1932, Rv0054, Rv1080c, Rv3418c, Rv3914, Rv1636 and Rv0009) that were overexpressed
in the presence of drugs. Among them, Rv2623, Rv1827 and Rv1636 were identified as proteins with unknown function.
InterProScan and molecular docking revealed that the conserved domain of hypothetical proteins interact with OFX and
MOX which indicate a probable inhibition/modulation of the functioning of these proteins by both drugs, which might be
overexpressed to overcome this effect.
