Estudio de cepas de Mycobacterium leprae colombiano causantes de múltiples episodios sintomáticos de lepra post poliquimioterapia

ilustraciones, graficas

Autores:: Chavarro Portillo, Bibiana

Tipo de recurso:: Doctoral thesis

Fecha de publicación:: 2021

Institución:: Universidad Nacional de Colombia

Repositorio:: Universidad Nacional de Colombia

Idioma:: spa

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dc.title.spa.fl_str_mv	Estudio de cepas de Mycobacterium leprae colombiano causantes de múltiples episodios sintomáticos de lepra post poliquimioterapia
dc.title.translated.eng.fl_str_mv	Study of Colombian strains of Mycobacterium leprae causing multiple symptomatic episodes of post-polychemotherapy leprosy
title	Estudio de cepas de Mycobacterium leprae colombiano causantes de múltiples episodios sintomáticos de lepra post poliquimioterapia
spellingShingle	Estudio de cepas de Mycobacterium leprae colombiano causantes de múltiples episodios sintomáticos de lepra post poliquimioterapia 610 - Medicina y salud Recurrencia Mycobacterium leprae Recurrence Mycobacterium leprae Genotipo Reinfección Células de Schwann Recaída Genotype Schwann Cells Relapse Reinfection
title_short	Estudio de cepas de Mycobacterium leprae colombiano causantes de múltiples episodios sintomáticos de lepra post poliquimioterapia
title_full	Estudio de cepas de Mycobacterium leprae colombiano causantes de múltiples episodios sintomáticos de lepra post poliquimioterapia
title_fullStr	Estudio de cepas de Mycobacterium leprae colombiano causantes de múltiples episodios sintomáticos de lepra post poliquimioterapia
title_full_unstemmed	Estudio de cepas de Mycobacterium leprae colombiano causantes de múltiples episodios sintomáticos de lepra post poliquimioterapia
title_sort	Estudio de cepas de Mycobacterium leprae colombiano causantes de múltiples episodios sintomáticos de lepra post poliquimioterapia
dc.creator.fl_str_mv	Chavarro Portillo, Bibiana
dc.contributor.advisor.none.fl_str_mv	Soto Ospina, Carlos Yesid
dc.contributor.author.none.fl_str_mv	Chavarro Portillo, Bibiana
dc.contributor.projectleader.none.fl_str_mv	Guerrero Guerrero Martha Inirida
dc.contributor.researchgroup.spa.fl_str_mv	Bioquímica y Biología Molecular de las Micobacterias
dc.contributor.orcid.spa.fl_str_mv	https://orcid.org/0000-0001-7186-2028
dc.contributor.researchgate.spa.fl_str_mv	https://www.researchgate.net/profile/Bibiana-Chavarro-Portillo
dc.subject.ddc.spa.fl_str_mv	610 - Medicina y salud
topic	610 - Medicina y salud Recurrencia Mycobacterium leprae Recurrence Mycobacterium leprae Genotipo Reinfección Células de Schwann Recaída Genotype Schwann Cells Relapse Reinfection
dc.subject.decs.spa.fl_str_mv	Recurrencia Mycobacterium leprae
dc.subject.decs.eng.fl_str_mv	Recurrence Mycobacterium leprae
dc.subject.proposal.spa.fl_str_mv	Genotipo Reinfección
dc.subject.proposal.eng.fl_str_mv	Células de Schwann Recaída Genotype Schwann Cells Relapse Reinfection
description	ilustraciones, graficas
publishDate	2021
dc.date.issued.none.fl_str_mv	2021-07-26
dc.date.accessioned.none.fl_str_mv	2023-06-01T13:03:48Z
dc.date.available.none.fl_str_mv	2023-06-01T13:03:48Z
dc.type.spa.fl_str_mv	Trabajo de grado - Doctorado
dc.type.driver.spa.fl_str_mv	info:eu-repo/semantics/doctoralThesis
dc.type.version.spa.fl_str_mv	info:eu-repo/semantics/acceptedVersion
dc.type.coar.spa.fl_str_mv	http://purl.org/coar/resource_type/c_db06
dc.type.content.spa.fl_str_mv	Text
dc.type.redcol.spa.fl_str_mv	http://purl.org/redcol/resource_type/TD
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status_str	acceptedVersion
dc.identifier.uri.none.fl_str_mv	https://repositorio.unal.edu.co/handle/unal/83938
dc.identifier.instname.spa.fl_str_mv	Universidad Nacional de Colombia
dc.identifier.reponame.spa.fl_str_mv	Repositorio Institucional Universidad Nacional de Colombia
dc.identifier.repourl.spa.fl_str_mv	https://repositorio.unal.edu.co
url	https://repositorio.unal.edu.co/handle/unal/83938 https://repositorio.unal.edu.co
identifier_str_mv	Universidad Nacional de Colombia Repositorio Institucional Universidad Nacional de Colombia
dc.language.iso.spa.fl_str_mv	spa
language	spa
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dc.publisher.spa.fl_str_mv	Universidad Nacional de Colombia
dc.publisher.program.spa.fl_str_mv	Bogotá - Ciencias - Doctorado en Biotecnología
dc.publisher.faculty.spa.fl_str_mv	Facultad de Ciencias
dc.publisher.branch.spa.fl_str_mv	Universidad Nacional de Colombia - Sede Bogotá
institution	Universidad Nacional de Colombia
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spelling	Atribución-NoComercial-SinDerivadas 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Soto Ospina, Carlos Yesid90f333e0838e289f724edbb356042e46600Chavarro Portillo, Bibiana9b7808f945f66df32401fcd73d42513d600Guerrero Guerrero Martha IniridaBioquímica y Biología Molecular de las Micobacteriashttps://orcid.org/0000-0001-7186-2028https://www.researchgate.net/profile/Bibiana-Chavarro-Portillo2023-06-01T13:03:48Z2023-06-01T13:03:48Z2021-07-26https://repositorio.unal.edu.co/handle/unal/83938Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.coilustraciones, graficasLa lepra es una enfermedad dermato-neurológica crónica, causada por Mycobacterium leprae, que en Colombia causa cerca de 400 casos nuevos cada año. La lepra se trata con una poliquimioterapia (PQT) y su eficacia es establecida por el seguimiento de casos recurrentes de la enfermedad. Debido a que la recurrencia no puede ser diferenciada en recaída o reinfección clínicamente, en el presente estudio, usamos técnicas de secuenciación total de ADN (genoma) y ARN (transcriptoma), con el fin de conocer algunas características genómicas y transcriptómicas de cepas de M. leprae asociadas con múltiples episodios de lepra post-PQT en Colombia. A partir de biopsias provenientes del diagnóstico inicial y durante la recurrencia de la enfermedad, se aisló ADN y se realizó la secuenciación total de genomas de M. leprae causantes de cada evento y se analizaron in silico los conjuntos de secuencias resultantes. Los análisis de genómica comparativa de las cepas de M. leprae causantes de eventos recurrentes permitieron establecer tres hallazgos importantes: i) encontrar ciertas características genómicas que podrían diferenciar una recaída de una recaída y reinfección, ii) la relación genética entre cepas colombianas y cepas antiguas y modernas , además de cepas aisladas en otros hospederos, como el armadillo de nueve bandas y ardillas de cola roja y iii) establecer posibles efectos de las mutaciones identificadas en los genomas analizados. Por otra parte, también se pudo establecer la capacidad infectiva de cepas de M. leprae relacionadas con un evento inicial en comparación con cepas asociadas a eventos recurrentes en un modelo in vitro de infección de células de Schwann. Se pudo observar que la entrada inicial de M. leprae a las células de Schwann no depende de las características inherentes de las cepas (vivas o muertas, de pacientes de eventos recurrentes o nuevos) ni de la carga bacteriana usada para la infección; pero la capacidad de infectar más células a través del tiempo si depende de la viabilidad del bacilo. Los análisis transcripcionales muestran la actividad de genes involucrados en la virulencia y supervivencia, además de los genes codificantes de proteínas de choque térmico, los cuales favorecen la supervivencia de M. leprae en condiciones de estrés o durante el cultivo in vitro. Como un marcador de patogenicidad, mediante qPCR, se evaluaron los niveles de expresión de siete genes implicados en la síntesis de PGL-1 durante la infección de células de Schwann. Los resultados mostraron una expresión diferencial de ciertos genes que se sugieren una capacidad metabólica disminuida en el caso de M. leprae provenientes de pacientes con recaída. (Texto tomado de la fuente)Leprosy is a chronic dermato-neurological disease caused by Mycobacterium leprae, which in Colombia causes about 400 new cases each year. Leprosy is treated with multidrug therapy (MDT) or polychemotherapy (PQT), and its efficacy is established by monitoring recurrent cases of the disease. Because recurrence cannot be clinically differentiated into relapse or reinfection, in the present study, we used total DNA (genome) and RNA (transcriptome) sequencing technique, in order to know some genomic and transcriptomic characteristics of M. leprae strains associated with multiple episodes of post-PQT leprosy in Colombia. From biopsies of initial diagnosis and during disease recurrence, DNA was isolated, and total genomes of M. leprae causing each event were sequence. The resulting sets of sequences were analyzed in silico. The comparative genomic analyzes of the M. leprae strains causing recurrent events allowed to us stablish three important findings: i) find certain genomic characteristics that could differentiate between relapse and reinfection, ii) the genetic relationship between Colombian strains and ancient, modern strains and strains isolated in other hosts, non-humans and iii) establish possible effects of the mutations identified in the genomes analyzed. An in vitro model of Schwann cell infection could establish the infective capacity of M. leprae strains from initial events compared to strains associated with recurrent events. It could be observed that the initial entry of M. leprae into Schwann cells does not depend on the inherent characteristics of the strains of patients with recurrent or new events or the bacterial load used for infection; but the ability to infect more cells over time depends on the genomic or metabolic characteristics of the bacillus. Transcriptional analyzes show the activity of genes involved in survival, in addition to genes encoding heat shock proteins, which favor the survival of M. leprae under stress conditions or during in vitro culture. As a marker of pathogenicity, by means of qPCR, the expression levels of seven genes involved in the synthesis of PGL-1 during the infection of Schwann cells were evaluated. The results showed a differential expression of certain genes that suggest a decreased metabolic capacity in the case of M. leprae from patients with relapse.DoctoradoDoctor en Biotecnología160 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Ciencias - Doctorado en BiotecnologíaFacultad de CienciasUniversidad Nacional de Colombia - Sede Bogotá610 - Medicina y saludRecurrenciaMycobacterium lepraeRecurrenceMycobacterium lepraeGenotipoReinfecciónCélulas de SchwannRecaídaGenotypeSchwann CellsRelapseReinfectionEstudio de cepas de Mycobacterium leprae colombiano causantes de múltiples episodios sintomáticos de lepra post poliquimioterapiaStudy of Colombian strains of Mycobacterium leprae causing multiple symptomatic episodes of post-polychemotherapy leprosyTrabajo de grado - Doctoradoinfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/acceptedVersionhttp://purl.org/coar/resource_type/c_db06Texthttp://purl.org/redcol/resource_type/TDBritton WJ, Lockwood DNJ. 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International journal of leprosy and other mycobacterial diseases: official organ of the International Leprosy Association. 1993;61: 600–604.Convocatoria de Doctorados Nacionales 727 - 2015Ministerio de Ciencia y TecnologiaEstudiantesGrupos comunitariosInvestigadoresLICENSElicense.txtlicense.txttext/plain; charset=utf-85879https://repositorio.unal.edu.co/bitstream/unal/83938/1/license.txteb34b1cf90b7e1103fc9dfd26be24b4aMD51ORIGINAL53133739.2021.pdf53133739.2021.pdfTesis de Doctorado en Biotecnologíaapplication/pdf3507767https://repositorio.unal.edu.co/bitstream/unal/83938/2/53133739.2021.pdf96f444b0ba5f02080c24eb686e45ad7dMD52THUMBNAIL53133739.2021.pdf.jpg53133739.2021.pdf.jpgGenerated Thumbnailimage/jpeg4657https://repositorio.unal.edu.co/bitstream/unal/83938/3/53133739.2021.pdf.jpg444330209a3819b68acf6352d3dd6597MD53unal/83938oai:repositorio.unal.edu.co:unal/839382023-08-07 23:03:38.367Repositorio Institucional Universidad Nacional de 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Estudio de cepas de Mycobacterium leprae colombiano causantes de múltiples episodios sintomáticos de lepra post poliquimioterapia

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