Estudi del transcriptoma de l’Escherichia coli adherent-invasiva (AIEC) per desxifrar les bases moleculars implicades en la seva patogenicitat
Adherent-invasive Escherichia coli (AIEC) is a bacterium found in the intestine that can adhere to and invade intestinal epithelial cells and to survive and replicate inside macrophages. Although it has also been detected in healthy individuals, this bacterium is more frequently found in patients wi...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/692407 |
| Acceso en línea: | http://hdl.handle.net/10803/692407 |
| Access Level: | acceso embargado |
| Palabra clave: | Malaltia de Crohn Enfermedad de Crohn Crohn's disease Escherichia coli adherent-invasiva Escherichia coli adherente-invasivo Adherent-invasive Escherichia coli Arginina Arginine Àcid colànic Ácido colánico Colanic acid Transcriptòmica comparativa Transcriptómica comparativa Comparative transcriptomics Biomarcadors Biomarcadores Biomarkers 579 616.3 |
| Sumario: | Adherent-invasive Escherichia coli (AIEC) is a bacterium found in the intestine that can adhere to and invade intestinal epithelial cells and to survive and replicate inside macrophages. Although it has also been detected in healthy individuals, this bacterium is more frequently found in patients with Crohn's disease, a chronic inflammatory bowel disease. The conditions of the inflamed intestine favor the survival and colonization of AIEC, while AIEC also contribute to increased inflammation and intestinal damage. AIEC are genetically similar to non-pathogenic strains of intestinal E. coli (non-AIEC), although the latter are not virulent and generally do not cause damage. In fact, no gene or genetic variant has yet been detected that allows differentiation between AIEC and non-AIEC, making their identification in the laboratory very difficult. Our hypothesis is that the pathogenicity of AIEC is due to differential gene expression between these strains and non-AIEC. The aim of this thesis is to detect these differences in gene expression between AIEC and non-AIEC and to study their implication in pathogenicity. Changes in gene expression are observed depending on the conditions in which the bacteria are found. For this reason, gene expression was analyzed during the infection of cell cultures. We have detected several genes that may be relevant in the pathogenicity of AIEC and that could be used as molecular markers for their identification. Among these, we have focused on genes that are part of the arginine and colanic acid biosynthesis pathways. To understand the relation between these two pathways and the pathogenicity of AIEC, mutants were generated and characterized in the laboratory. It was observed that the regulator ArgR, which regulates the expression of arginine biosynthesis genes, is also involved in controlling other genes, some of which are involved in AIEC's pathogenic characteristics of motility, cellular invasion or intracellular survival, and biofilm formation. On the other hand, inducing the expression of colanic acid biosynthesis genes resulted in increased motility, while the adhesion to cells and biofilm formation capacities decreased. This finding has allowed us to relate the expression of these genes and various pathogenicity characteristics, indicating the importance of these genes in AIEC. Therefore, this thesis has identified differences in gene expression between AIEC and non-AIEC strains and related them to their pathogenicity, as well as proposed molecular markers for AIEC identification |
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