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dc.contributor.authorKumar, Rupesh
dc.contributor.authorMadhumathi, Bhavani Shankar
dc.contributor.authorNagaraja, V.
dc.date.accessioned2017-02-21T09:53:24Z-
dc.date.available2017-02-21T09:53:24Z-
dc.date.issued2014
dc.identifier.citationKumar, R; Madhumathi, BS; Nagaraja, V, Molecular Basis for the Differential Quinolone Susceptibility of Mycobacterial DNA Gyrase. Antimicrobial Agents And Chemotherapy 2014, 58 (4) 2013-2020, http://dx.doi.org/10.1128/AAC.01958-13en_US
dc.identifier.citationAntimicrobial Agents And Chemotherapyen_US
dc.identifier.citation58en_US
dc.identifier.citation4en_US
dc.identifier.issn0066-4804
dc.identifier.urihttp://hdl.handle.net/10572/2600-
dc.descriptionRestricted Accessen_US
dc.description.abstractDNA gyrase is a type II topoisomerase that catalyzes the introduction of negative supercoils in the genomes of eubacteria. Fluoroquinolones (FQs), successful as drugs clinically, target the enzyme to trap the gyrase-DNA complex, leading to the accumulation of double-strand breaks in the genome. Mycobacteria are less susceptible to commonly used FQs. However, an 8-methoxy-substituted FQ, moxifloxacin (MFX), is a potent antimycobacterial, and a higher susceptibility of mycobacterial gyrase to MFX has been demonstrated. Although several models explain the mechanism of FQ action and gyrase-DNA-FQ interaction, the basis for the differential susceptibility of mycobacterial gyrase to various FQs is not understood. We have addressed the basis of the differential susceptibility of the gyrase and revisited the mode of action of FQs. We demonstrate that FQs bind both Escherichia coli and Mycobacterium tuberculosis gyrases in the absence of DNA and that the addition of DNA enhances the drug binding. The FQs bind primarily to the GyrA subunit of mycobacterial gyrase, while in E. coli holoenzyme is the target. The binding of MFX to GyrA of M. tuberculosis correlates with its effectiveness as a better inhibitor of the enzyme and its efficacy in cell killing.en_US
dc.description.uri1098-6596en_US
dc.description.urihttp://dx.doi.org/10.1128/AAC.01958-13en_US
dc.language.isoEnglishen_US
dc.publisherAmerican Society Microbiologyen_US
dc.rights@American Society Microbiology, 2014en_US
dc.subjectMicrobiologyen_US
dc.subjectPharmacology & Pharmacyen_US
dc.subjectResistance-Determining Regionen_US
dc.subjectEscherichia-Colien_US
dc.subjectTopoisomerase-Iven_US
dc.subjectFluoroquinolone Actionen_US
dc.subjectIia Topoisomerasesen_US
dc.subjectMagnesium-Ionsen_US
dc.subjectMechanismen_US
dc.subjectBindingen_US
dc.subjectInhibitionen_US
dc.subjectTuberculosisen_US
dc.titleMolecular Basis for the Differential Quinolone Susceptibility of Mycobacterial DNA Gyraseen_US
dc.typeArticleen_US
Appears in Collections:Research Articles (Nagaraja, V.)

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