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Un antibiótico peptídico-carboximetilo-citidina de caballo de Troya de Bacillus amyloliquefaciens
Marina Serebryakova1,2, Darya Tsibulskaya1, Olga Mokina1,3
1Institute of Gene Biology, Russian Academy of Science , 34/5 Vavilov str., 119334 Moscow, Russia.
Journal of the American Chemical Society
|December 10, 2016
Resumen
Los investigadores descubrieron un nuevo antibiótico parecido a la microcina C de Bacillus amyloliquefaciens. Este nuevo compuesto se dirige a la aspartil-tRNA sintetasa y presenta carboximetilación para prevenir la resistencia bacteriana.
Área de la Ciencia:
- Microbiología
- La bioquímica
- Biología molecular
Sus antecedentes:
- La microcina C es un antibiótico peptídico adenilado de caballo de Troya.
- Inhibe la aspartil-tRNA sintetasa después del procesamiento intracelular.
- La adenilación de los precursores del péptido es catalizada por las adenililtransferasas tipo MccB THIF NAD/FAD.
Objetivo del estudio:
- Caracterizar un nuevo compuesto parecido a la microcina de Bacillus amyloliquefaciens.
- Investigar las modificaciones enzimáticas involucradas en su síntesis.
- Evaluar su actividad biológica y su potencial para superar la resistencia.
Principales métodos:
- Ensayos in vitro y celulares con el uso de Bacillus amyloliquefaciens
- Ensayos enzimáticos para estudiar la actividad de MccB y MccS.
- Análisis de la estructura y función de la microcina.
Principales resultados:
- El Bacillus amyloliquefaciens MccB une un monofosfato de citidina terminal a los péptidos precursores.
- La fracción de citosina se modifica aún más por carboximetilación, mediada por MccB y MccS.
- Estos compuestos modificados parecidos a la microcina C son activos contra la aspartil-tRNA sintetasa y resisten los mecanismos de resistencia comunes.
Conclusiones:
- Se ha identificado una nueva clase de antibióticos similares a la microcina C con modificaciones terminales de la citosina.
- La carboximetilación de la porción de citosina es una modificación clave que mejora la actividad biológica y previene la resistencia.
- Estos hallazgos amplían el repertorio conocido de modificaciones de péptidos para el desarrollo de nuevos antibióticos.
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