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Un autoinducidor de quórum producido por el huésped controla una decisión de lisis-lisogenia de fagos
Justin E Silpe1, Bonnie L Bassler2
1Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Cell
|December 18, 2018
Resumen
Vibrio cholerae y sus fagos usan la misma molécula de señal, DPO, para la patogénesis. El fago VqmA activa los genes de virulencia del huésped, mientras que el huésped VqmA los reprime, revelando una interacción compleja en la infección bacteriana.
Área de la Ciencia:
- Microbiología
- Biología molecular
- Bacteriología
Sus antecedentes:
- Vibrio cholerae utiliza un sistema de detección de quórum (QS) que incluye 3,5-dimetilpirazina-2-ol (DPO) y VqmA (VqmAVc) para regular la virulencia y la formación de biopelículas.
- El gen vqmA se encuentra en las especies de Vibrio y en el vibriófago VP882, lo que sugiere una transferencia génica horizontal y mecanismos reguladores compartidos.
Objetivo del estudio:
- Investigar el papel de la VqmA codificada por los fagos (VqmAFago) en la interacción entre V. cholerae y su fago infectante.
- Comprender cómo los fagos integran las señales derivadas del huésped en sus decisiones de ciclo de vida (lisis-lisogenia).
- Para explorar el potencial de reprogramación de los fagos para controlar las infecciones bacterianas.
Principales métodos:
- Análisis comparativo de las interacciones de VqmAVc y VqmAPhage con el DPO.
- Investigación de la función antirepresora de los fagos y su interferencia con los fagos represores relacionados.
- Ensayos funcionales para evaluar la activación de la regulación del huésped VqmAVc por VqmAFago.
- Reprogramación de los fagos para responder a las señales definidas por el usuario para la inducción de la lisis.
Principales resultados:
- El fago VqmA se une al DPO producido por el huésped, iniciando el programa de lisis del fago.
- VqmAPhage actúa a través de un antirepresor que inactiva el represor de fagos e interfiere con los represores de fagos relacionados.
- VqmA Fago activa el huésped VqmA Vc regulon, lo que demuestra una interacción reguladora asimétrica.
- El huésped VqmAVc no puede inducir la lisis mediada por fagos, destacando la influencia unidireccional de los fagos.
Conclusiones:
- Tanto V. cholerae como sus fagos infectantes dependen de la misma molécula de señal (DPO) para la patogénesis.
- Los fagos aprovechan la maquinaria QS del huésped para su propia propagación, integrando las señales del huésped en las decisiones de lisis-lisogenia.
- La reprogramación de fagos ofrece una estrategia potencial para la intervención terapéutica contra las infecciones bacterianas.
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