Caracterización genética mediante secuenciación de siguiente generación de Candida auris aislada de infecciones invasivas en hospitales de Bogotá

dc.contributor.advisorChala Palacios, María del Socorro
dc.contributor.advisorPinzón Velasco, Andrés
dc.contributor.authorGutiérrez Vásquez, Elizabeth
dc.contributor.researchgroupGrupo de Laboratorios de Salud pública (SDS)spa
dc.contributor.rightsholderSandra Liliana Gómez
dc.date.accessioned2022-08-03T20:51:52Z
dc.date.available2022-08-03T20:51:52Z
dc.date.issued2022
dc.descriptionilustraciones, graficas, mapasspa
dc.description.abstractCandida auris es un hongo patógeno emergente y oportunista caracterizado por su difícil identificación con pruebas de diagnóstico convencionales, lo cual retrasa el tratamiento del paciente. Además, es común que éste patógeno presente resistencia a la primera línea de antimicóticos utilizados habitualmente en el tratamiento de infecciones por hongos (azoles, polienos y equinocandinas). Está resistencia ha sido asociada a mutaciones genómicas, las cuales también han sido encontradas en otras especies patógenas del género Candida. Por otro lado, la falta de información sobre su diversidad genética en la mayoría de aislamientos ha impedido estudiar a fondo el impacto de estas mutaciones y de la epidemiologia genómica de este microorganismo. En este estudio se buscó caracterizar aislamientos de C. auris enviados al laboratorio de salud pública de Bogotá como parte del programa de vigilancia epidemiológica. En un estudio descriptivo y de corte trasversal, 20 aislamientos obtenidos de hospitales de Bogotá fueron identificados como C. auris mediante técnicas fenotípicas y caracterizados molecularmente usando espectometría de masas maldiTOF y NGS (Secuenciación de Nueva Generación). La identificación de los 20 aislamientos se confirmó mediante análisis filogenéticos. La diversidad genética observada fue baja y sugirió la existencia del efecto de selección direccional o selección de fondo. Se identificaron cuatro genotipos por sus perfiles MLST que podrían optimizarse ya que no describeron la totalidad de la diversidad genética en los aislamientos bogotanos. Aunque no se encontraron mutaciones asociadas a resistencia, sí se encontraron duplicaciones en varios genes, incluyendo adp1, pmi1, zwF1b y se presentaron cambios de mutaciones parsimoniosas vps13, zwF1b, cdr1 y erg3. También se observaron sustitución de aminoácidos en algunos de estos genes: erg3 (H771R), erg11 (G459S) y rpn2 (K898E). Los análisis de diversidad genética y filogenéticos mostraron una baja diversidad genética en los 20 aislamientos bogotanos, todos estos agrupándose dentro del clado IV de Suramérica y presentando un número relativamente bajo de diferencias de SNP entre ellos, aunque lo suficientemente alto como para sugerir ausencia de clonalidad en estos aislamientos. Además, las desviaciones del modelo de neutralidad selectiva sugieren que la baja diversidad podría explicarse por un modelo de expansión de la población. A partir de estos hallazgos, se sugiere que C. auris ha tenido una trasmisión continua y generalizada en el territorio colombiano. (Texto tomado de la fuente)spa
dc.description.abstractCandida auris is an emerging, opportunistic and pathogenic fungus characterized by its difficult identification through conventional diagnostic tests, thus delaying the treatment of the patient. Furthermore, it is usual for this pathogen to be resistant to the antifungals of first line utilized commonly for treating fungal infections (azoles, polyenes and echinocandins). This resistance has been associated to genomic mutations, which have also been found in other pathogenic species of Candida. On the other hand, the lack of information about the genetic diversity in the great majority of isolates has hampered to deeply study the impact of this mutations and the genomic epidemiology of this pathogen. This study aimed at characterizing C. auris isolates sent to the public health laboratory of Bogotá as part of an epidemiological surveillance program. In this descriptive and cross-sectional study, 20 isolates obtained from hospitals in Bogotá were identified as C. auris through phenotypic techniques and molecularly characterized using MALDI-TOF mass spectrometry and NGS (Next Generation Sequencing). The identification of the 20 isolates was confirmed by phylogenetic analysis. The genetic diversity observed was low and suggested the presence of effects of directional selection or background selection. Four genotypes were identified using their MLST profiles, as though this technique could be optimized since these profiles did not describe the complete genetic diversity presented by Bogota isolates. Although resistance-associated mutations were not found, duplications were found in several genes, including adp1, pmi1, zwF1b, and parsimonious mutation changes vps13, zwF1b, cdr1, and erg3. Some of these genes also presented the following amino acid substitutions: erg3 (H771R), erg11 (G459S), and rpn2 (K898E). The genetic diversity and phylogenetic analyzes showed a low genetic diversity in the 20 Bogotá isolates, all of them grouped within the clade IV of South America and presenting a relatively low number of SNP differences between them, although this number was high enough to suggest the absence of clonality in these isolates. Furthermore, the deviations from the model of selective neutrality suggest that a population expansion model could explain the low diversity. From these findings, it is suggested that C. auris has had a continuous and generalized transmission in the Colombian territory.eng
dc.description.degreelevelMaestríaspa
dc.description.degreenameMagíster en Ciencias - Microbiologíaspa
dc.description.researchareaBiología Molecular de Agentes Infecciososspa
dc.description.sponsorshipEl Laboratorio de Salud Pública de la Secretaría Distrital de Salud es una entidad pública, encargada del desarrollo de acciones técnico-administrativas realizadas en atención a las personas y a la salud ambiental con propósitos de vigilancia en salud pública, vigilancia y control sanitario, gestión de la calidad e investigación. Los ejes estratégicos sobre los cuales el Laboratorio de Salud Pública basa su gestión para orientar sus procesos y competencias son los siguientes: 1. Vigilancia en Salud Pública. Eje estratégico orientado al desarrollo de acciones para apoyar la vigilancia en salud pública y la vigilancia y control sanitario. 2. Gestión de la Calidad. Eje estratégico orientado al desarrollo de acciones para el mejoramiento progresivo en el cumplimiento de los estándares óptimos de calidad. 3. Prestación de Servicios. Eje estratégico orientado al desarrollo de acciones para el mejoramiento de la capacidad de oferta de servicios desde los laboratorios públicos y privados en los diferentes niveles territoriales. 4. Investigación. Eje estratégico orientado al desarrollo de acciones para apoyar la investigación desde el laboratorio y contribuir con el Sistema Nacional de Ciencia y Tecnología en el desarrollo de investigaciones en el área de la salud. El Laboratorio de Salud Pública tiene implementado un Sistema de Gestión de la Calidad bajo la norma NTC-ISO/IEC 17025:2017, a través del cual se demuestra la competencia técnica de las metodologías analíticas que realiza en las áreas de Vigilancia de Enfermedades de Eventos de Interés en Salud Pública y Vigilancia del Ambiente y el Consumo. Misión Atender las necesidades requeridas en el Distrito Capital, relacionadas con actividades de investigación, vigilancia y control en Salud Pública, asesoría, asistencia técnica y control de calidad a la Red Distrital de Laboratorios; a través de la realización de ensayos confiables y oportunos, soportados por personal profesional idóneo, comprometido y altamente calificado, enmarcados en un Sistema de Gestión de Calidad, con recursos, infraestructura adecuada y desarrollo tecnológico permanente. Visión Ser reconocido como modelo en desarrollo de procesos de gestión de calidad en laboratorios de salud pública y como un centro de alta tecnología con la realización de pruebas analíticas acreditadas bajo la norma ISO 17025:2017, que apoyen la investigación, vigilancia y control de eventos de interés en salud colectiva zonal, nacional e internacional, con el mejor servicio en asesoría, asistencia técnica, control de calidad y apoyo diagnóstico a la Red Distrital de laboratorios. Áreas del Laboratorio Por favor haga clic en cada uno de los siguientes enlaces: 1. Vigilancia de eventos de interés en salud pública – VEISP 2. Vigilancia y control sanitario – VCS 3. Gestión de la calidad 4. Epidemiología y sistemas de información 5. Investigacionesspa
dc.format.extentxxii, 88 páginasspa
dc.format.mimetypeapplication/pdfspa
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/81775
dc.language.isospaspa
dc.publisherUniversidad Nacional Colombiaspa
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotáspa
dc.publisher.departmentInstituto de Biotecnología (IBUN)spa
dc.publisher.facultyFacultad de Cienciasspa
dc.publisher.placeBogotá, Colombiaspa
dc.publisher.programBogotá - Ciencias - Maestría en Ciencias - Microbiologíaspa
dc.relation.indexedRedColspa
dc.relation.indexedLaReferenciaspa
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dc.rights.accessrightsinfo:eu-repo/semantics/openAccessspa
dc.rights.licenseAtribución-SinDerivadas 4.0 Internacionalspa
dc.rights.urihttp://creativecommons.org/licenses/by-nd/4.0/spa
dc.subject.ddc570 - Biología::576 - Genética y evoluciónspa
dc.subject.proposalCandida aurisspa
dc.subject.proposalResistencia antimicóticosspa
dc.subject.proposalDiagnóstico erróneospa
dc.subject.proposalMutacionesspa
dc.subject.proposalAntifungal resistanceeng
dc.subject.proposalAntifungal resistanceeng
dc.subject.proposalMutationseng
dc.subject.proposalMisdiagnosiseng
dc.subject.unescoHongos patógenos
dc.subject.unescoPathogenic fungi
dc.titleCaracterización genética mediante secuenciación de siguiente generación de Candida auris aislada de infecciones invasivas en hospitales de Bogotáspa
dc.title.translatedGenetic characterization by next generation sequencing of Candida auris isolated from invasive infections in hospitals of Bogotáeng
dc.typeTrabajo de grado - Maestríaspa
dc.type.coarhttp://purl.org/coar/resource_type/c_bdccspa
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aaspa
dc.type.contentTextspa
dc.type.driverinfo:eu-repo/semantics/masterThesisspa
dc.type.redcolhttp://purl.org/redcol/resource_type/TMspa
dc.type.versioninfo:eu-repo/semantics/acceptedVersionspa
dcterms.audience.professionaldevelopmentInvestigadoresspa
dcterms.audience.professionaldevelopmentMaestrosspa
oaire.accessrightshttp://purl.org/coar/access_right/c_abf2spa
oaire.awardtitleCaracterización genética mediante secuenciación de siguiente generación de Candida auris aislada de infecciones invasivas en Hospitales de Bogotáspa
oaire.fundernameSecretaria Distrital de Salud de Bogotá Laboratorio de Salud Públicaspa

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