First characterization of a microsporidial triosephosphate isomerase and the biochemical mechanisms of its inactivation to propose a new druggable target
Por:
Garcia-Torres, Itzhel, De la Mora-De la Mora, Ignacio, Hernandez-Alcantara, Gloria, Molina-Ortiz, Dora, Caballero-Salazar, Silvia, Olivos-Garcia, Alfonso, Nava, Gabriela, Lopez-Velazquez, Gabriel, Enriquez-Flores, Sergio
Publicada:
5 jun 2018
Categoría:
Multidisciplinary
Resumen:
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. © 2018 The Author(s).
Filiaciones:
Garcia-Torres, Itzhel:
Inst Nacl Pediat, Lab Errores Innatos Metab & Tamiz, Grp Invest Biomol, Mexico City 04530, DF, Mexico
De la Mora-De la Mora, Ignacio:
Inst Nacl Pediat, Lab Errores Innatos Metab & Tamiz, Grp Invest Biomol, Mexico City 04530, DF, Mexico
Hernandez-Alcantara, Gloria:
Univ Nacl Autonoma Mexico, Fac Med, Dept Bioquim, Mexico City 04510, DF, Mexico
Molina-Ortiz, Dora:
Inst Nacl Pediat, Lab Toxicol Genet, Mexico City 04530, DF, Mexico
Caballero-Salazar, Silvia:
Inst Nacl Pediat, Lab Parasitol Expt, Mexico City 04530, DF, Mexico
Olivos-Garcia, Alfonso:
Univ Nacl Autonoma Mexico, Fac Med, Unidad Invest Med Expt, Mexico City 04510, DF, Mexico
Hosp Gen, Mexico City 04510, DF, Mexico
Nava, Gabriela:
Univ Nacl Autonoma Mexico, Fac Med, Dept Microbiol & Parasitol, Mexico City 04510, DF, Mexico
Lopez-Velazquez, Gabriel:
Inst Nacl Pediat, Lab Errores Innatos Metab & Tamiz, Grp Invest Biomol, Mexico City 04530, DF, Mexico
Enriquez-Flores, Sergio:
Inst Nacl Pediat, Lab Errores Innatos Metab & Tamiz, Grp Invest Biomol, Mexico City 04530, DF, Mexico
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