title: Proteomic analysis of ofloxacin-mono resistant Mycobacterium tuberculosis isolates.
abstract: 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.
authors.affiliation: Department of Biochemistry, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra 282004, India.. Electronic address: jalma.manju@gmail.com.
authors.forename: Manju
authors.initials: M
authors.lastname: Lata
authors.affiliation: Department of Biochemistry, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra 282004, India.. Electronic address: divakarsharma88@gmail.com.
authors.forename: Divakar
authors.initials: D
authors.lastname: Sharma
authors.affiliation: Department of Biochemistry, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra 282004, India.. Electronic address: nirmaladeo2000@gmail.com.
authors.forename: Nirmala
authors.initials: N
authors.lastname: Deo
authors.affiliation: School of Studies in Zoology, Jiwaji University, Gwalior, India. Electronic address: pk_tiwari@hotmail.com.
authors.forename: Pramod Kumar
authors.initials: PK
authors.lastname: Tiwari
authors.affiliation: Department of Biochemistry, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra 282004, India.. Electronic address: abd1109@rediffmail.com.
authors.forename: Deepa
authors.initials: D
authors.lastname: Bisht
authors.affiliation: Department of Biochemistry, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra 282004, India.. Electronic address: drvenkatesan1952@gmail.com.
authors.forename: Krishnamurthy
authors.initials: K
authors.lastname: Venkatesan
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D024881:Drug Resistance, Bacterial; D005260:Female; D006801:Humans; D008297:Male; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification / Q000378:metabolism*; D015242:Ofloxacin / Q000494:pharmacology*; D040901:Proteomics
chemical_list: D001426:Bacterial Proteins; D015242:Ofloxacin