Caracterización genómica y transcriptómica de los aislamientos de Leishmania (V.) braziliensis con diferente patrón de susceptibilidad a la Anfotericina B (AmB).

ilustraciones a color, diagramas

Autores:: Clavijo Vanegas, Ana María

Tipo de recurso:

Fecha de publicación:: 2024

Institución:: Universidad Nacional de Colombia

Repositorio:: Universidad Nacional de Colombia

Idioma:: spa

id	UNACIONAL2_dd5c727d656d3875083a83f3ebffd674
oai_identifier_str	oai:repositorio.unal.edu.co:unal/86558
network_acronym_str	UNACIONAL2
network_name_str	Universidad Nacional de Colombia
repository_id_str
dc.title.spa.fl_str_mv	Caracterización genómica y transcriptómica de los aislamientos de Leishmania (V.) braziliensis con diferente patrón de susceptibilidad a la Anfotericina B (AmB).
dc.title.translated.eng.fl_str_mv	Genomic and transcriptomic characterization of Leishmania (V.) braziliensis isolates with different susceptibility pattern to amphotericin B (AmB).
title	Caracterización genómica y transcriptómica de los aislamientos de Leishmania (V.) braziliensis con diferente patrón de susceptibilidad a la Anfotericina B (AmB).
spellingShingle	Caracterización genómica y transcriptómica de los aislamientos de Leishmania (V.) braziliensis con diferente patrón de susceptibilidad a la Anfotericina B (AmB). 610 - Medicina y salud::616 - Enfermedades 570 - Biología::576 - Genética y evolución 610 - Medicina y salud::615 - Farmacología y terapéutica Vacunas contra la Leishmaniasis Anfotericina B Secuenciación completa del genoma Farmacogenética Variantes farmacogenómicas Leishmaniasis vaccines Amphotericin B Whole genome sequencing Pharmacogenetics Pharmacogenomic variants Infección parasitaria Leishmania Baja susceptibilidad Tratamiento Anfotericina B Parasitic infection Leishmania Low susceptibility Treatment Amphotericin B
title_short	Caracterización genómica y transcriptómica de los aislamientos de Leishmania (V.) braziliensis con diferente patrón de susceptibilidad a la Anfotericina B (AmB).
title_full	Caracterización genómica y transcriptómica de los aislamientos de Leishmania (V.) braziliensis con diferente patrón de susceptibilidad a la Anfotericina B (AmB).
title_fullStr	Caracterización genómica y transcriptómica de los aislamientos de Leishmania (V.) braziliensis con diferente patrón de susceptibilidad a la Anfotericina B (AmB).
title_full_unstemmed	Caracterización genómica y transcriptómica de los aislamientos de Leishmania (V.) braziliensis con diferente patrón de susceptibilidad a la Anfotericina B (AmB).
title_sort	Caracterización genómica y transcriptómica de los aislamientos de Leishmania (V.) braziliensis con diferente patrón de susceptibilidad a la Anfotericina B (AmB).
dc.creator.fl_str_mv	Clavijo Vanegas, Ana María
dc.contributor.advisor.spa.fl_str_mv	Echeverry Gaitán, María Clara Clavijo-Ramírez, Carlos Arturo
dc.contributor.author.spa.fl_str_mv	Clavijo Vanegas, Ana María
dc.contributor.researchgroup.spa.fl_str_mv	Infecciones y Salud en El Trópico
dc.contributor.orcid.spa.fl_str_mv	Clavijo Vanegas, Ana María [0000000221592768]
dc.contributor.cvlac.spa.fl_str_mv	Clavijo Vanegas, Ana María [0000146519]
dc.subject.ddc.spa.fl_str_mv	610 - Medicina y salud::616 - Enfermedades 570 - Biología::576 - Genética y evolución 610 - Medicina y salud::615 - Farmacología y terapéutica
topic	610 - Medicina y salud::616 - Enfermedades 570 - Biología::576 - Genética y evolución 610 - Medicina y salud::615 - Farmacología y terapéutica Vacunas contra la Leishmaniasis Anfotericina B Secuenciación completa del genoma Farmacogenética Variantes farmacogenómicas Leishmaniasis vaccines Amphotericin B Whole genome sequencing Pharmacogenetics Pharmacogenomic variants Infección parasitaria Leishmania Baja susceptibilidad Tratamiento Anfotericina B Parasitic infection Leishmania Low susceptibility Treatment Amphotericin B
dc.subject.decs.spa.fl_str_mv	Vacunas contra la Leishmaniasis Anfotericina B Secuenciación completa del genoma Farmacogenética Variantes farmacogenómicas
dc.subject.decs.eng.fl_str_mv	Leishmaniasis vaccines Amphotericin B Whole genome sequencing Pharmacogenetics Pharmacogenomic variants
dc.subject.proposal.spa.fl_str_mv	Infección parasitaria Leishmania Baja susceptibilidad Tratamiento Anfotericina B
dc.subject.proposal.eng.fl_str_mv	Parasitic infection Leishmania Low susceptibility Treatment Amphotericin B
description	ilustraciones a color, diagramas
publishDate	2024
dc.date.accessioned.none.fl_str_mv	2024-07-18T15:00:53Z
dc.date.available.none.fl_str_mv	2024-07-18T15:00:53Z
dc.date.issued.none.fl_str_mv	2024
dc.type.spa.fl_str_mv	Trabajo de grado - Maestría
dc.type.driver.spa.fl_str_mv	info:eu-repo/semantics/masterThesis
dc.type.version.spa.fl_str_mv	info:eu-repo/semantics/acceptedVersion
dc.type.content.spa.fl_str_mv	Text
dc.type.redcol.spa.fl_str_mv	http://purl.org/redcol/resource_type/TM
status_str	acceptedVersion
dc.identifier.uri.none.fl_str_mv	https://repositorio.unal.edu.co/handle/unal/86558
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/86558 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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spelling	Reconocimiento 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Echeverry Gaitán, María Clarae040dbadd72121efdf7220643864e808Clavijo-Ramírez, Carlos Arturo75b9265ba83a38076e8f4e14bc259e76600Clavijo Vanegas, Ana María4bdfcd50013d69a00a7d12386ce9b1d1Infecciones y Salud en El TrópicoClavijo Vanegas, Ana María [0000000221592768]Clavijo Vanegas, Ana María [0000146519]2024-07-18T15:00:53Z2024-07-18T15:00:53Z2024https://repositorio.unal.edu.co/handle/unal/86558Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustraciones a color, diagramasLa leishmaniasis es una enfermedad causada por un parásito perteneciente al género Leishmania, el cual se transmite en el nuevo mundo por una mosca vector hematófaga perteneciente al género Lutzomyia, mediante ciclos de infección zoonótica y antroponótica. La leishmaniasis presenta manifestaciones viscerales (LV), cutáneas (LC) o mucosas (LM). En Colombia la forma más común es la LC y está asociada principalmente a las especies de Leishmania pertenecientes al subgénero Viannia [L.(V.) braziliensis, L. (V.) panamensis y L. (V.) guyanensis]. El tratamiento de la LC se hace de manera sistémica mediante el uso de fármacos con alto nivel de toxicidad como son las sales de antimonio (SbV), tratamiento de primera línea y la anfotericina B (AmB) que se emplea como tratamiento de segunda línea. Datos de meta-análisis estiman la falla terapéutica en el tratamiento de LC con SbV en un 25% de los casos. Adicionalmente, en Colombia se ha informado la circulación de aislamientos clínicos de L.(V.) braziliensis y L.(V.) panamensis con susceptibilidad reducida a la AmB. Una de las posibles causas de falla terapéutica en LC es la resistencia por parte del parásito, no obstante, los mecanismos moleculares asociados a resistencia a la AmB en Leishmania spp, son poco conocidos y han sido estudiados principalmente en cepas del laboratorio de especies del subgénero Leishmania Leishmania. Por lo tanto, en la presente investigación, se emplearon aislamientos clínicos de L.(V.) braziliensis, en los que previamente se determinó un patrón diferencial de susceptibilidad a la AmB in vitro, y se estudiaron factores potencialmente asociados al patrón de susceptibilidad, con el fin de proponer posibles moléculas o vías metabólicas involucradas en la respuesta in vitro de L.(V.) braziliensis a la AmB. Entre los factores estudiados están el mantenimiento en cultivo del aislamiento clínico y las diferencias genómicas y de niveles de transcrito entre aislamientos con diferente susceptibilidad. Para lograr el propósito mencionado, se realizaron ensayos de dosis-respuesta a la AmB en los dos estadios parasitarios, se analizó el genoma de los aislamientos clínicos, se evaluaron niveles de transcrito de genes seleccionados y se adelantaron ensayos preliminares de sobre-expresión génica. Mediante esta aproximación, se determinó que en los aislamientos clínicos de L.(V.) braziliensis, no existe relación entre susceptibilidad in vitro a la AmB y el mantenimiento in vitro. Con el análisis de la secuenciación del genoma, se evidenció aumento en el número de copias de algunos genes codificantes de enzimas relacionadas con la maquinaria de respiración mitocondrial y la biosíntesis de la biopeterina en aislamientos clínicos con baja susceptibilidad in vitro a la AmB. Se encontró la presencia de la región LD1, un locus multigénico ampliamente estudiado en Leishmania spp. Y adicionalmente, se estableció que el incremento en el número de copias de un gen, no necesariamente implica el aumento en los niveles de transcrito correspondiente. (Texto tomado de la fuente)Leishmaniasis is a disease caused by a parasite belonging to the genus Leishmania, which is transmitted in the New World by a hematophagous female sandfly vector belonging to the genus Lutzomyia, through zoonotic and anthroponotic infection cycles. Leishmaniasis presents visceral (VL), cutaneous (CL) or mucosal (ML) manifestations. In Colombia, the most common form is CL and is mainly associated with Leishmania species belonging to the subgenus Viannia [L.(V.) braziliensis, L. (V.) panamensis and L. (V.) guyanensis]. CL is treated systemically using highly toxic drugs such as antimony salts (SbV) as first-line treatment and amphotericin B (Amphotericin B (AmB) as second-line treatment. Meta-analysis data estimate therapeutic failure in the treatment of CL with SbV in 25% of cases. Additionally, clinical isolates of L.(V.) braziliensis and L.(V.) panamensis with reduced susceptibility to AmB have been reported in Colombia. One of the possible causes of therapeutic failure in CL is resistance by the parasite; however, the molecular mechanisms associated with AmB resistance in Leishmania spp. are poorly understood and have been studied mainly in laboratory strains of species of the subgenus Leishmania Leishmania. Therefore, in the present investigation, clinical isolates of L.(V.) braziliensis, in which a differential pattern of susceptibility to AmB in vitro was previously determined, were used. Factors potentially associated with the susceptibility pattern were studied in order to propose possible molecules or metabolic pathways involved in the in vitro response of L.(V.) braziliensis to AmB. Among the factors studied are the maintenance in the culture of the clinical isolate and the genomic and transcript level differences between isolates with different susceptibility. To achieve the study purpose, dose-response assays to AmB were performed in the two parasite stages, the genome of clinical isolates was analyzed, transcript levels of selected genes were evaluated, and preliminary gene overexpression assays were performed. This approach determined that in clinical isolates of L.(V.) braziliensis, there is no relationship between in vitro susceptibility to AmB and in vitro maintenance. The genome sequencing analysis revealed increased copies of some genes encoding enzymes related to the mitochondrial respiration machinery and the biosynthesis of biopeterin in clinical isolates with low in vitro susceptibility to AmB. The presence of the LD1 region, a multigene locus widely studied in Leishmania spp. was found. Additionally, it was established that the increase in the number of copies of a gene does not necessarily imply an increase in the corresponding transcript levels. (Texto tomado de la fuente)MaestríaMagister en Infecciones y Salud en el TrópicoMecanismos moleculares de farmacorresistencia en parásitos de la familia Trypanosomatidae80 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Medicina - Maestría en Infecciones y Salud en el TrópicoFacultad de MedicinaBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá610 - Medicina y salud::616 - Enfermedades570 - Biología::576 - Genética y evolución610 - Medicina y salud::615 - Farmacología y terapéuticaVacunas contra la LeishmaniasisAnfotericina BSecuenciación completa del genomaFarmacogenéticaVariantes farmacogenómicasLeishmaniasis vaccinesAmphotericin BWhole genome sequencingPharmacogeneticsPharmacogenomic variantsInfección parasitariaLeishmaniaBaja susceptibilidadTratamientoAnfotericina BParasitic infectionLeishmaniaLow susceptibilityTreatmentAmphotericin BCaracterización genómica y transcriptómica de los aislamientos de Leishmania (V.) braziliensis con diferente patrón de susceptibilidad a la Anfotericina B (AmB).Genomic and transcriptomic characterization of Leishmania (V.) braziliensis isolates with different susceptibility pattern to amphotericin B (AmB).Trabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMAcestor, N., Zíková, A., Dalley, R., Anupama, A., Panigrahi, A., y Stuart, K. 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Molecular and Cellular Proteomics, 7(7), 1286–1296. https://doi.org/10.1074/mcp.M700490-MCP200“Caracterización genotípica y fenotípica de aislamientos clínicos de Leishmania braziliensis con disminución en la sensibilidad para Glucantime® y Anfotericina B”Ministerio de Ciencia, Tecnología e Innovación – (Minciencias)BibliotecariosEstudiantesInvestigadoresMaestrosPersonal de apoyo escolarPúblico generalLICENSElicense.txtlicense.txttext/plain; charset=utf-85879https://repositorio.unal.edu.co/bitstream/unal/86558/3/license.txteb34b1cf90b7e1103fc9dfd26be24b4aMD53ORIGINAL1013678476-2024.pdf1013678476-2024.pdfTesis de Maestría en Infecciones y Salud en el Trópicoapplication/pdf1377990https://repositorio.unal.edu.co/bitstream/unal/86558/4/1013678476-2024.pdfcae25fbff33f592a4de624d69f5523cbMD54THUMBNAIL1013678476-2024.pdf.jpg1013678476-2024.pdf.jpgGenerated 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

Caracterización genómica y transcriptómica de los aislamientos de Leishmania (V.) braziliensis con diferente patrón de susceptibilidad a la Anfotericina B (AmB).

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