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Evaluación de la susceptibilidad a la anfotericina B de parásitos de Leishmania del subgénero Viannia con resistencia adquirida in vitro a miltefosina

dc.rights.licenseAtribución-NoComercial-SinDerivadas 4.0 Internacional
dc.contributor.advisorEcheverry Gaitán, María Clara
dc.contributor.advisorOvalle Bracho, Clemencia Elena
dc.contributor.authorCastaño Rodríguez, Marcela
dc.date.accessioned2020-09-04T20:49:31Z
dc.date.available2020-09-04T20:49:31Z
dc.date.issued2020-03-19
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/78396
dc.description.abstractDentro de los fármacos usados como segunda línea de tratamiento para la leishmaniasis están la anfotericina B y la miltefosina. Los dos medicamentos interfieren con la composición de lípidos en la membrana parasitaria y existe evidencia tanto in vitro como en aislamientos clínicos de resistencia cruzada entre estos medicamentos en especies pertenecientes al subgénero Leishmania Leishmania spp. En Suramérica las especies predominantes pertenecen al subgénero Leishmania Viannia spp. El presente estudio evaluó la ocurrencia de disminución de susceptibilidad a anfotericina B in vitro en parásitos de Leishmania Viannia spp con previa exposición a miltefosina. Los parásitos evaluados correspondían a clones inducidos resistentes y a aislamientos de pacientes tratados con miltefosina. El establecimiento de dosis efectivas 50 (EC50) se hizo por el método de rezarsurina, la cuantificación de mRNA de genes involucrados en la biosíntesis y transporte de lípidos se realizó por RT-qPCR. En los parásitos con inducción experimental de resistencia a miltefosina se observó concomitantemente el aumento en la tolerancia a anfotericina B; acompañado por una disminución en la expresión de enzimas involucradas en la biosíntesis de esterol, esterol metil transferasa y latosterol oxidasa; de una proteína de unión endosoma-lisosoma vamp y del transportador de miltefosina. El limitado número de aislamientos clínicos no presentó una correlación entre los valores EC50 calculados para los dos fármacos. Lo anterior permite concluir que es posible generar resistencia cruzada entre miltefosina y anfotericina b en parásitos del subgénero Leishmania Viannia y se requiere estudios con mayor número de aislamiento
dc.description.abstractAmong the second-line drugs used to treat Leishmaniasis are amphotericin B and miltefosine, both drugs interfere with the lipid composition of the parasite membrane, there is cross-resistance evidence in vitro and in clinical isolates in species of the Leishmania subgenus, Leishmania leishmania spp. In South America the predominant species belong to the subgenus Leishmania viannia spp. The aim of the study was to evaluate the susceptibility to amphotericin B in vitro in parasites of Leishmania viannia spp with previous exposition to miltefosine. The evaluated parasites were clones induce resistant to miltefosine and clinical isolates that have been previously expose to miltefosine in Leishmaniasis treatment. Resarzurin method was used to stablish the EC50, mRNA quantification of genes involve in sterol biosynthesis was done through a RT-qPCR. It was observed in induce resistant clones to miltefosine a higher tolerance to amphotericin B, accompany by a loss of expression of enzymes involved in the sterol biosynthesis, sterol methyl transferase and lathosterol oxidase, of a protein involve in membrane fusion of endosome-lysosome, vamp and miltefosina transporter. The limit number of clinical isolates did not follow the change in susceptibility observed for the induce resistant clones in both drugs. As a conclusion, is possible to induce cross-resistance between amphotericin B and miltefosina in Leishmania viannia parasites and a bigger sample size of clinical isolates is needed to assess cross-resistance.
dc.description.sponsorshipColciencias
dc.format.extent97
dc.format.mimetypeapplication/pdf
dc.language.isospa
dc.rightsDerechos reservados - Universidad Nacional de Colombia
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc500 - Ciencias naturales y matemáticas::507 - Educación, investigación, temas relacionados
dc.titleEvaluación de la susceptibilidad a la anfotericina B de parásitos de Leishmania del subgénero Viannia con resistencia adquirida in vitro a miltefosina
dc.typeOtro
dc.rights.spaAcceso abierto
dc.description.projectProyecto número 212074455505 acuerdo 467-2017
dc.description.additionalLínea de investigación: Leishmaniasis
dc.type.driverinfo:eu-repo/semantics/other
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dc.publisher.programBogotá - Medicina - Maestría en Infecciones y Salud en el Trópico
dc.contributor.researchgroupInfecciones y Salud en el Trópico
dc.description.degreelevelMaestría
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotá
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dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.subject.proposalmiltefosine
dc.subject.proposalMiltefosina
dc.subject.proposalanfotericina B
dc.subject.proposalamphotericin B
dc.subject.proposalcross-resistance
dc.subject.proposalresistencia cruzada
dc.subject.proposalLeishmania braziliensis
dc.subject.proposalLeishmania braziliensis
dc.type.coarhttp://purl.org/coar/resource_type/c_1843
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.contentText
oaire.accessrightshttp://purl.org/coar/access_right/c_abf2


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