| Autor: |
García-Torres I; Grupo de Investigación en Biomoléculas, Laboratorio de Errores Innatos del Metabolismo y Tamiz, Instituto Nacional de Pediatría, Ciudad de México, 04530, Mexico., De la Mora-De la Mora I; Grupo de Investigación en Biomoléculas, Laboratorio de Errores Innatos del Metabolismo y Tamiz, Instituto Nacional de Pediatría, Ciudad de México, 04530, Mexico., Hernández-Alcántara G; Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, 04510, Mexico., Molina-Ortiz D; Laboratorio de Toxicología Genética, Instituto Nacional de Pediatría, Ciudad de México, 04530, Mexico., Caballero-Salazar S; Laboratorio de Parasitología Experimental, Instituto Nacional de Pediatría, Ciudad de México, 04530, Mexico., Olivos-García A; Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México y Hospital General, Ciudad de México, 04510, Mexico., Nava G; Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, 04510, Mexico., López-Velázquez G; Grupo de Investigación en Biomoléculas, Laboratorio de Errores Innatos del Metabolismo y Tamiz, Instituto Nacional de Pediatría, Ciudad de México, 04530, Mexico. glv_1999@yahoo.com., Enríquez-Flores S; Grupo de Investigación en Biomoléculas, Laboratorio de Errores Innatos del Metabolismo y Tamiz, Instituto Nacional de Pediatría, Ciudad de México, 04530, Mexico. sergioenriquez@ciencias.unam.mx. |
| Abstrakt: |
The microsporidia are a large group of intracellular parasites with a broad range of hosts, including humans. Encephalitozoon intestinalis is the second microsporidia species most frequently associated with gastrointestinal disease in humans, especially immunocompromised or immunosuppressed individuals, including children and the elderly. The prevalence reported worldwide in these groups ranges from 0 to 60%. Currently, albendazole is most commonly used to treat microsporidiosis caused by Encephalitozoon species. However, the results of treatment are variable, and relapse can occur. Consequently, efforts are being directed toward identifying more effective drugs for treating microsporidiosis, and the study of new molecular targets appears promising. These parasites lack mitochondria, and oxidative phosphorylation therefore does not occur, which suggests the enzymes involved in glycolysis as potential drug targets. Here, we have for the first time characterized the glycolytic enzyme triosephosphate isomerase of E. intestinalis at the functional and structural levels. Our results demonstrate the mechanisms of inactivation of this enzyme by thiol-reactive compounds. The most striking result of this study is the demonstration that established safe drugs such as omeprazole, rabeprazole and sulbutiamine can effectively inactivate this microsporidial enzyme and might be considered as potential drugs for treating this important disease. |
