Proteomic analysis of ofloxacin-mono resistant Mycobacterium tuberculosis isolates

• Proteins showed increased intensity in M. tuberculosis of OFX resistant (six) and OFX resistant induced with OFX (fourteen).
• Out of them four proteins (Rv2744c, Rv2140c, Rv3551 and Rv0148) were with unknown functions.
• Molecular docking revealed that OFX interacts with conserved motifs of these hypothetical proteins.
• We hypothesized that these proteins might be neutralizing the effect of OFX & contributing to OFX resistance.

Drug resistance particularly, multi drug resistance tuberculosis (MDR-TB) has emerged as a major problem in the chemotherapy of tuberculosis. Ofloxacin (OFX) has been used as second-line drug against MDR-TB. The principal target of the OFX is DNA gyrase encoded by gyrA and gyrB genes. Many explanations have been proposed for drug resistance to OFX but still some mechanisms are unknown. As proteins manifest most of the biological processes, these are attractive targets for developing drugs and diagnostics/therapeutics. We examined the OFX resistant Mycobacterium tuberculosis isolates by proteomic approach (2DE-MALDI-TOF-MS) and bioinformatic tools under OFX induced conditions. Our study showed fourteen proteins (Rv0685, Rv0363c, Rv2744c, Rv3803c, Rv2534c, Rv2140c, Rv1475c, Rv0440, Rv2245, Rv1436, Rv3551, Rv0148, Rv2882c and Rv0733) with increased intensities in OFX resistant and OFX induced as compared to susceptible isolates. Bioinformatic analysis of hypothetical proteins (Rv2744c, Rv2140c, Rv3551 and Rv0148) revealed the presence of conserved motifs and domains. Molecular docking showed proper interaction of OFX with residues of conserved motifs. These proteins might be involved in the OFX modulation/neutralization and act as novel resistance mechanisms as well as potential for diagnostics and drug targets against OFX resistance.This article is part of a Special Issue entitled: Proteomics in India.

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