| TAZ-TFM-2023-109 |
Caracterización multi-ómica de la función de VirR en el remodelado de la pared celular en Mycobacterium tuberculosis
Bertol Faure, Jorge
Sanz Remón, Joaquín (dir.) ; Marchante Hueso, Ignacio (dir.)
Universidad de Zaragoza,
CIEN,
2023
Máster Universitario en Biofísica y Biotecnología Cuantitativa / Master in Biophysics and Quantitative Biotechnology
Resumen: VirR, a LytR_C domain containing protein, has been linked to the regulation of production of extracellular vesicles (EVs) in Mycobacterium tuberculosis by maintaining cell wall integrity. To test its regulatory role in vesiculogenesis, proteomic and transcriptomic profiles from a mutant strain of M. tuberculosis with an inactive phenotype of the VirR protein (VirR-KO) were obtained, as well as from the wild-type strain H37RV. The VirR KO mutant, as ascertained through previous results of our collaborators, presented an abnormal cell wall morphology linked to higher permeability, lower virulence and an increased production of extracellular vesicles.
Transcriptomic data was collected from whole cell lysates from each strain, revealing major differences concerning host defense and host-induced stress responses, as well as gene regulation, and metal ion import and export, which is coherent with the divergent virulence and secretory profiles of H37RV and the VirR-KO mutant. Furthermore, these analyses also revealed divergent expression levels for genes involved in mRNA translation, stabilization, and metabolism; thus pointing to the existence of relevant post-transcriptional regulatory mechanisms mediated by VirR.
To test that hypothesis, proteomic analyses were performed on whole cell lysates and isolated extracellular vesicles from each strain, revealing largely disjoint sets of differentially expressed proteins with respect to mRNAs, further pointing to the relevance of post-transcriptional mechanisms in the regulatory role of VirR. Differential expression analysis of the proteins revealed greater differences between extracellular vesicles from different strains than between whole cell lysates, indicating a primary role for VirR in the proteomic enrichment profile of EVs.
Taken together, our results highlight a relevant regulatory role for virR that leans both on transcriptional and post-transcriptional mechanisms, which significantly mediates the amount and function of EVs secreted by Mycobacterium tuberculosis.
Transcriptomic data was collected from whole cell lysates from each strain, revealing major differences concerning host defense and host-induced stress responses, as well as gene regulation, and metal ion import and export, which is coherent with the divergent virulence and secretory profiles of H37RV and the VirR-KO mutant. Furthermore, these analyses also revealed divergent expression levels for genes involved in mRNA translation, stabilization, and metabolism; thus pointing to the existence of relevant post-transcriptional regulatory mechanisms mediated by VirR.
To test that hypothesis, proteomic analyses were performed on whole cell lysates and isolated extracellular vesicles from each strain, revealing largely disjoint sets of differentially expressed proteins with respect to mRNAs, further pointing to the relevance of post-transcriptional mechanisms in the regulatory role of VirR. Differential expression analysis of the proteins revealed greater differences between extracellular vesicles from different strains than between whole cell lysates, indicating a primary role for VirR in the proteomic enrichment profile of EVs.
Taken together, our results highlight a relevant regulatory role for virR that leans both on transcriptional and post-transcriptional mechanisms, which significantly mediates the amount and function of EVs secreted by Mycobacterium tuberculosis.
Tipo de Trabajo Académico: Trabajo Fin de Master
Notas: El máster correspondiente es el actual Máster Universitario en Biofísica y Biotecnología Cuantitativa, no aparece en el listado así que he escogido el nombre anterior, Máster Universitario en Biotecnología Cuantitativa
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El registro pertenece a las siguientes colecciones:
Trabajos académicos > Trabajos Académicos por Centro > Facultad de Ciencias
Trabajos académicos > Trabajos fin de máster