Construcción y caracterización parcial de un doble mutante de Mycobacterium tuberculosis en los transportadores de membrana CtpF y MmpL7

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dc.contributor.advisorSoto Ospina, Carlos Yesid
dc.contributor.authorCruz Cacais, Alver Antonio
dc.contributor.orcidCruz Cacais, Alver Antonio [000000018208863X]
dc.contributor.researchgroupBioquímica y Biología Molecular de las Micobacterias
dc.coverage.countryColombia
dc.date.accessioned2025-09-09T14:05:21Z
dc.date.available2025-09-09T14:05:21Z
dc.date.issued2025
dc.descriptionilustraciones (principalmente a color), diagramas, fotografías, mapaspa
dc.description.abstractLa tuberculosis (TB), producida por su agente etiológico Mycobacterium tuberculosis (Mtb), es actualmente la primera causa de muerte por un agente infeccioso a nivel mundial. Sin embargo, la única vacuna autorizada contra la TB, el bacilo Calmette–Guérin (BCG), no logra proteger de forma eficiente contra la enfermedad. En este sentido, el desarrollo de nuevos candidatos a vacuna contra la TB, que reemplacen a la BCG es absolutamente prioritario. Actualmente, ha surgido mucho interés en el uso de proteínas de membrana como dianas de atenuación de Mtb encaminado a la construcción de mutantes atenuados con potencial vacunal. Por ejemplo, CtpF, una ATPasa tipo P transportadora de Ca2+, relevante en la virulencia y supervivencia del bacilo tuberculoso, se muestra como una buena diana de atenuación de Mtb. Por otra parte, MmpL7 es una proteína transportadora no relacionada con CtpF, implicada en la biosíntesis de lípidos de Mtb, incluyendo los dimicocerosatos de tiocerol (PDIM), considerados factores de virulencia. La deleción del gen mmpL7 en el genoma micobacteriano conduce a la atenuación del bacilo tuberculoso. El objetivo del presente trabajo es obtener y evaluar preliminarmente un doble mutante defectivo en los genes ctpF y mmpL7, desprovisto parcialmente de resistencia antibiótica, y que pueda ser probado en estudios preclínicos de atenuación en modelo celular y animal como un posible candidato a vacuna viva contra la TB. (Texto tomado de la fuente)spa
dc.description.abstractTuberculosis (TB), caused by the etiological agent Mycobacterium tuberculosis (Mtb), remains the leading cause of death from a single infectious agent worldwide. The only licensed TB vaccine, Bacillus Calmette–Guérin (BCG), provides limited and inconsistent protection, underscoring the urgent need for more effective alternatives. Membrane proteins have recently gained attention as promising targets for Mtb attenuation, enabling the generation of live attenuated mutants with vaccine potential. CtpF, a P-type ATPase involved in Ca²⁺ transport, plays a critical role in Mtb virulence and survival, making it an attractive candidate for genetic inactivation. In parallel, MmpL7, an unrelated membrane transporter required for the biosynthesis of phthiocerol dimycocerosates (PDIM), recognized virulence factors, has also been implicated in pathogenesis. Deletion of the mmpL7 gene leads to attenuation of the bacillus. Here, we describe the generation and preliminary characterization of a double mutant lacking ctpF and mmpL7, engineered to be partially devoid of antibiotic resistance markers. This strain is intended for preclinical evaluation in cellular and animal models as a potential live attenuated TB vaccine candidate.eng
dc.description.curricularareaQuímica.Sede Bogotá
dc.description.degreelevelMaestría
dc.description.degreenameMagíster en Ciencias – Bioquímica
dc.description.researchareaHospedero-Patógeno
dc.description.researcharea[Virulencia y latencia de las micobacterias]
dc.description.sponsorshipDivisión de Investigación de Bogotá-DIB por financiar el proyecto “Construcción y caracterización parcial del mutante de Mycobacterium tuberculosis en los transportadores de membrana CtpF y MmpL7, con potencial vacunal.” en la Convocatoria para el apoyo a proyectos de investigación y creación artística de la Sede Bogotá de la Universidad Nacional De Colombia-2019.
dc.format.extent109 páginas
dc.format.mimetypeapplication/pdf
dc.identifier.instnameUniversidad Nacional de Colombiaspa
dc.identifier.reponameRepositorio Institucional Universidad Nacional de Colombiaspa
dc.identifier.repourlhttps://repositorio.unal.edu.co/spa
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/88662
dc.language.isospaspa
dc.publisherUniversidad Nacional de Colombia
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotá
dc.publisher.facultyFacultad de Ciencias
dc.publisher.placeBogotá, Colombia
dc.publisher.programBogotá - Ciencias - Maestría en Ciencias - Bioquímica
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dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/
dc.subject.ddc540 - Química y ciencias afines
dc.subject.ddc570 - Biología::572 - Bioquímica
dc.subject.decsMycobacterium tuberculosis -- Químicaspa
dc.subject.decsMycobacterium tuberculosis -- Chemistryeng
dc.subject.decsTuberculosis -- Microbiologíaspa
dc.subject.decsTuberculosis -- Microbiologyeng
dc.subject.decsTuberculosis -- Etiologíaspa
dc.subject.decsTuberculosis -- Etiologyeng
dc.subject.decsATPasas Tipo P -- Químicaspa
dc.subject.decsP-type ATPases -- Chemistryeng
dc.subject.decsProteínas mutantes -- Biosíntesisspa
dc.subject.decsMutant proteins -- Biosynthesiseng
dc.subject.proposalMtbspa
dc.subject.proposalMutante atenuadospa
dc.subject.proposalATPasa tipo Pspa
dc.subject.proposalTransportador de lípidosspa
dc.subject.proposalMtbspa
dc.subject.proposalMtbeng
dc.subject.proposalTuberculosiseng
dc.subject.proposalAttenuated mutanteng
dc.subject.proposalP-type ATPaseeng
dc.subject.proposalLipid transportereng
dc.titleConstrucción y caracterización parcial de un doble mutante de Mycobacterium tuberculosis en los transportadores de membrana CtpF y MmpL7spa
dc.title.translatedConstruction and partial characterization of a double mutant of Mycobacterium tuberculosis in the membrane transporters CtpF and MmpL7eng
dc.typeTrabajo de grado - Maestría
dc.type.coarhttp://purl.org/coar/resource_type/c_bdcc
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.contentText
dc.type.driverinfo:eu-repo/semantics/masterThesis
dc.type.redcolhttp://purl.org/redcol/resource_type/TM
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dcterms.audience.professionaldevelopmentEstudiantes
dcterms.audience.professionaldevelopmentInvestigadores
dcterms.audience.professionaldevelopmentPúblico general
oaire.accessrightshttp://purl.org/coar/access_right/c_abf2
oaire.awardtitleConstrucción y caracterización parcial del mutante de Mycobacterium tuberculosis en los transportadores de membrana CtpF y MmpL7, con potencial vacunal
oaire.fundernameDivisión de Investigación de Bogotá-DIB

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