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Una toxina bacteriana que controla la progresión del ciclo celular como una proteína similar a la desoxirribonucleasa
1Section of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale School of Medicine, New Haven, CT 06536, USA.
Science (New York, N.Y.)
|October 13, 2000
Resumen
La subunidad CdtB de la toxina distendente citotólica bacteriana (CDT), una desoxirribonucleasa, causa la detención del ciclo celular y la muerte. Los mutantes que carecen de actividad de la desoxirribonucleasa no inducen estos efectos tóxicos.
Área de la Ciencia:
- Microbiología Microbiología.
- Biología celular Biología celular.
- Toxicología Toxicología.
Sus antecedentes:
- Los patógenos bacterianos utilizan toxinas como la toxina distendente citoleta (CDT) para inducir la muerte celular del huésped.
- La CDT causa la detención del ciclo celular, la distensión citoplasmática, la fragmentación de la cromatina y la muerte celular.
- La subunidad de la toxina CDT de Campylobacter jejuni, CdtB, posee actividad de desoxirribonucleasa tipo I.
Objetivo del estudio:
- Para investigar el papel de la actividad de la desoxirribonucleasa de CdtB en la citotoxicidad inducida por CDT.
- Para determinar si la función enzimática de CdtB es esencial para los efectos de la toxina en las células huésped.
Principales métodos:
- Expresión transitoria de CdtB en células de cultivo.
- Microinyección de CdtB purificado y sus mutantes.
- Análisis de la morfología celular, la progresión del ciclo celular y la integridad de la cromatina.
- Mutagenesis dirigida al sitio de CdtB para interrumpir los residuos catalíticos o de unión al magnesio.
Principales resultados:
- La expresión transitoria de CdtB causó una interrupción significativa de la cromatina en las células cultivadas.
- La microinyección de CdtB indujo la distensión citoplasmática y la detención del ciclo celular.
- Los mutantes CdtB defectuosos en la actividad de la desoxirribonucleasa no pudieron interrumpir la cromatina ni detener el ciclo celular.
- La holotoxina que contiene CdtB mutante no indujo la detención del ciclo celular o cambios morfológicos.
Conclusiones:
- La actividad de la desoxirribonucleasa de CdtB es crítica por su papel en la detención y muerte del ciclo celular mediada por toxinas distendentes citotólicas.
- La función enzimática de CdtB es necesaria para los efectos citotóxicos observados de CDT.
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