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Determinación del proteoma de la cepa VCG-1 de Plasmodium Vivax y caracterización de moléculas candidatas para su inclusión en el desarrollo de una vacuna

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dc.contributor.advisorPatarroyo, Manuel A.
dc.contributor.advisorMuro Álvarez, Antonio
dc.creatorMoreno Pérez, Darwin Andrés
dc.creator.degreeDoctor en Ciencias Biomédicas y Biológicasspa
dc.creator.degreetypeFull timespa
dc.date.accessioned2019-02-18T21:46:17Z
dc.date.available2019-02-18T21:46:17Z
dc.date.created2017-09-07
dc.date.issued2017
dc.descriptionLa identificación y caracterización de proteínas que utilizan los merozoitos de Plasmodium para invadir a su célula hospedera, representan una estrategia importante para desarrollar un método de control contra estos parásitos. A pesar de ello, la investigación básica en P. vivax está retrasada por su difícil propagación in vitro, debido a la preferencia que tiene el parásito por invadir reticulocitos, los cuales se encuentran en escaso porcentaje en sangre periférica de humanos adultos (1-2%) y son difíciles de obtener con alta pureza, en suficiente cantidad y totalmente viables. Como consecuencia de lo anterior, el conocimiento del número de moléculas que expresa P. vivax y cuáles de ellas son candidatas para componer una vacuna, es escaso. En este estudio, se evaluó el proteoma de una cepa de P. vivax adaptada a primates y se caracterizaron moléculas antigénicas y con capacidad de adhesión a reticulocitos humanos. En el análisis del proteoma de la cepa VCG-1 de P. vivax, se detectaron 734 proteínas, algunas esenciales en los pasos clave para establecer la invasión del merozoito a su célula diana. Además, se identificaron 811 componentes de eritrocitos (hospederos vitales de Plasmodium) del primate A. nancymaae, de los cuales 51 son proteínas integrales de membrana, 7 descritas como receptores de Plasmodium. Por otro lado, se identificó la presencia, transcripción y expresión de los genes codificantes de tres moléculas de P. vivax: PvARP, PvRBSA y PvGAMA, así como su antigenicidad. De particular interés, se encontró que PvRBSA y PvGAMA se unen en mayor proporción a reticulocitos que expresan el receptor CD71 de forma abundante (CD71hi), lo que sugiere que estas moléculas pueden estar participando en la selección preferencial que tienen los merozoitos de P. vivax por los reticulocitos humanos. Este es el primer estudio en Colombia donde se determina la composición proteica de una cepa de P. vivax adaptada a primates, así como la de eritrocitos de A. nancymaae. Como resultado más importante, se caracterizaron moléculas de P. vivax que son candidatos idóneos a ser evaluados como componentes de una vacuna contra la malaria causada por esta especie parasitaria.spa
dc.description.abstractIdentifying and characterising proteins which use Plasmodium merozoites to invade host cells represents an important strategy for developing a method for controlling these parasites. However, basic P. vivax research has been delayed due to difficulties in propagating it in vitro as the parasite prefers to invade reticulocytes; there is a low percentage of these in adult human peripheral blood (1%-2%) and they are difficult to obtain with high purity, in a sufficient amount and totally viable. Consequently, knowledge is scarce regarding the amount of molecules being expressed by P. vivax and which of them represent good candidates for inclusion in an effective vaccine. This study has been aimed at evaluating the proteome of a primate-adapted P. vivax strain; antigenic molecules able to bind to human reticulocytes have been characterised. Analysing the P. vivax VCG-1 strain proteome led to detecting 734 proteins, some of them essential in key steps for establishing merozoite invasion of target cells. Furthermore, 811 A. nancymaae primate erythrocyte components (vital Plasmodium hosts) were identified; 51 of them were integral membrane proteins, 7 described as Plasmodium receptors. The presence, transcription, expression and antigenicity of genes encoding three P. vivax molecules (PvARP, PvRBSA and PvGAMA) were identified. Particularly interesting was the finding that a higher percentage of PvRBSA and PvGAMA bound to reticulocytes abundantly expressing the CD71 receptor (CD71hi), thereby suggesting that these molecules could be participating in P. vivax merozoite preferential selection for human reticulocytes. This the first study in Colombia which has determined the protein composition of a primate-adapted P. vivax strain as well as A. nancymaae erythrocytes. More importantly, P. vivax molecules were characterised which appear to be suitable candidates for being evaluated as components of a vaccine against malaria caused by the parasite species.spa
dc.description.sponsorshipUniversidad del Rosariospa
dc.description.sponsorshipUniversidad de Salamancaspa
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.48713/10336_19098
dc.identifier.urihttp://repository.urosario.edu.co/handle/10336/19098
dc.language.isospa
dc.publisherUniversidad del Rosariospa
dc.publisher.departmentFacultad de Ciencias Naturales y Matemáticasspa
dc.publisher.programDoctorado en Ciencias Biomédicas y Biológicasspa
dc.rightsAtribución-NoComercial-SinDerivadas 2.5 Colombiaspa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
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dc.source.instnameinstname:Universidad del Rosariospa
dc.source.reponamereponame:Repositorio Institucional EdocURspa
dc.subjectPlasmodium vivaxspa
dc.subjectInvasiónspa
dc.subjectProteomaspa
dc.subjectAdhesiónspa
dc.subjectReticulocitosspa
dc.subject.ddcEnfermedadesspa
dc.subject.keywordPlasmodium vivaxspa
dc.subject.keywordInvasionspa
dc.subject.keywordReticulocytesspa
dc.subject.keywordProteomespa
dc.subject.keywordCharacterizationspa
dc.subject.lembMalariaspa
dc.subject.lembPlasmodium vivaxspa
dc.titleDeterminación del proteoma de la cepa VCG-1 de Plasmodium Vivax y caracterización de moléculas candidatas para su inclusión en el desarrollo de una vacunaspa
dc.typedoctoralThesiseng
dc.type.documentAnálisis de casospa
dc.type.hasVersioninfo:eu-repo/semantics/acceptedVersion
dc.type.spaTesis de doctoradospa
local.department.reportEscuela de Medicina y Ciencias de la Saludspa
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Doctorado en Ciencias Biomédicas y Biológicas