The Structural Modeling of the Interaction between Levofloxacin and the Mycobacterium tuberculosis Gyrase Catalytic Site Sheds Light on the Mechanisms of Fluoroquinolones Resistant Tuberculosis in Colombian Clinical Isolates

dc.creatorPeláez Jaramillo, Carlos Alberto
dc.creatorÁlvarez Zuluaga, Nataly
dc.creatorZapata, E.
dc.creatorMejía, G.I
dc.creatorRealpe, T.
dc.creatorAraque Marín, Predonel
dc.creatorRouzaud, F.
dc.creatorRobledo, J.
dc.date2023-06-01T11:28:10Z
dc.date2023-06-01T11:28:10Z
dc.date2014
dc.date.accessioned2024-04-23T18:14:09Z
dc.date.available2024-04-23T18:14:09Z
dc.identifierÁlvarez N, Zapata E, Mejía GI, Realpe T, Araque P, Peláez C, Rouzaud F, Robledo J. The structural modeling of the interaction between levofloxacin and the Mycobacterium tuberculosis gyrase catalytic site sheds light on the mechanisms of fluoroquinolones resistant tuberculosis in Colombian clinical isolates. Biomed Res Int. 2014;2014:367268. doi: 10.1155/2014/367268.
dc.identifier2314-6133
dc.identifierhttps://hdl.handle.net/10495/35210
dc.identifier10.1155/2014/367268
dc.identifier2314-6141
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/9230569
dc.descriptionABSTRACT: We compared the prevalence of levofloxacin (LVX) resistance with that of ofloxacin (OFX) and moxifloxacin (MFX) among multidrug resistant (MDR) MTB clinical isolates collected in Medellin, Colombia, between 2004 and 2009 and aimed at unraveling the underlying molecular mechanisms that explain the correlation between QRDR-A mutations and LVX resistance phenotype. We tested 104 MDR isolates for their susceptibility to OFX, MFX, and LVX. Resistance to OFX was encountered in 10 (9.6%) of the isolates among which 8 (7.7%) were also resistant to LVX and 6 (5.7%) to MFX. Four isolates resistant to the 3 FQ were harboring the Asp94Gly substitution, whilst 2 other isolates resistant to OFX and LVX presented the Ala90Val mutation. No mutations were found in the QRDR-B region.The molecular modeling of the interaction between LVX and the DNA-DNA gyrase complex indicates that the loss of an acetyl group in the Asp94Gly mutation removes the acid base interaction with LVX necessary for the quinolone activity. The Ala90Val mutation that substitutes a methyl for an isopropyl group induces a steric modification that blocks the LVX access to the gyrase catalytic site.
dc.descriptionCOL0007462
dc.format9
dc.formatapplication/pdf
dc.formatapplication/pdf
dc.languageeng
dc.publisherHindawi
dc.publisherGrupo Interdisciplinario de Estudios Moleculares
dc.publisherNueva York, Estados Unidos
dc.relationBiomed. Res. Int.
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightshttp://creativecommons.org/licenses/by/2.5/co/
dc.rightshttp://purl.org/coar/access_right/c_abf2
dc.rightshttps://creativecommons.org/licenses/by/4.0/
dc.subjectSustitución de Aminoácidos
dc.subjectAmino Acid Substitution
dc.subjectAntibacterianos
dc.subjectAnti-Bacterial Agents
dc.subjectProteínas Bacterianas
dc.subjectBacterial Proteins
dc.subjectDominio Catalítico
dc.subjectCatalytic Domain
dc.subjectFarmacorresistencia Bacteriana Múltiple
dc.subjectDrug Resistance, Multiple, Bacterial
dc.subjectLevofloxacino
dc.subjectLevofloxacin
dc.subjectMycobacterium tuberculosis
dc.subjectTuberculosis Resistente a Múltiples Medicamentos
dc.subjectTuberculosis, Multidrug-Resistant
dc.titleThe Structural Modeling of the Interaction between Levofloxacin and the Mycobacterium tuberculosis Gyrase Catalytic Site Sheds Light on the Mechanisms of Fluoroquinolones Resistant Tuberculosis in Colombian Clinical Isolates
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion
dc.typehttp://purl.org/coar/resource_type/c_2df8fbb1
dc.typehttps://purl.org/redcol/resource_type/ART
dc.typeArtículo de investigación


Este ítem pertenece a la siguiente institución