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La exotoxina pirogénica estreptocócica B divide el GSDMA y desencadena la piroptosis
Wanyan Deng1,2,3, Yang Bai1,4, Fan Deng1,4
1The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
Nature
|February 3, 2022
Resumen
La proteasa bacteriana SpeB de Streptococcus pyogenes divide la gasdermina A (GSDMA), iniciando la piroptosis. Esta activación de GSDMA es crucial para la defensa del huésped contra este peligroso patógeno de la piel.
Área de la Ciencia:
- Inmunología
- Microbiología
- Biología celular
Sus antecedentes:
- Las gasderminas (GSDMA-GSDME) son proteínas formadoras de poros centrales para la piroptosis, un mecanismo de muerte celular inflamatoria.
- Si bien se conocen los activadores de GSDMB-E, la vía de activación de GSDMA, que prevalece en la piel, sigue sin estar clara.
- Streptococcus pyogenes (GAS) es un importante patógeno bacteriano de la piel.
Objetivo del estudio:
- Para aclarar el mecanismo por el cual se activa GSDMA.
- Para investigar el papel de GSDMA en la defensa del huésped contra la infección por Streptococcus pyogenes.
Principales métodos:
- Ensayos in vitro para determinar la actividad de la proteasa SpeB en el GSDMA.
- Análisis del sitio de escisión de GSDMA y de los fragmentos resultantes.
- Evaluación de la inducción de la piroptosis en los queratinocitos.
- Evaluación de la respuesta inmune del huésped en ratones con deficiencia de Gsdma1 infectados con GAS.
Principales resultados:
- La GAS cisteína proteasa SpeB divide GSDMA en Gln246, generando un fragmento N-terminal activo.
- Este evento de escisión desencadena la piroptosis de los queratinocitos.
- Los ratones que carecen de Gsdma1 exhiben respuestas inmunes alteradas al GAS, lo que lleva a un aumento de la propagación bacteriana y la mortalidad.
- El GSDMA funciona como un sensor y sustrato para el SpeB, iniciando la piroptosis.
Conclusiones:
- La activación de GSDMA por GAS SpeB proporciona un mecanismo de huésped directo para controlar este patógeno.
- Esta vía destaca el papel crítico del GSDMA en la inmunidad de la piel y la defensa del huésped contra las infecciones bacterianas.
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