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El mecanismo de acción de la lisobactina
Wonsik Lee1, Kaitlin Schaefer1,2, Yuan Qiao1,2
1Department of Microbiology and Immunology, Harvard Medical School , Boston, Massachusetts 02115, United States.
Journal of the American Chemical Society
|December 20, 2015
Resumen
La actividad antibiótica de la lisobactina se deriva de la unión al lípido II, un componente clave en la síntesis de la pared celular bacteriana. Esta interacción específica interrumpe la división celular, lo que lleva a la muerte bacteriana.
Área de la Ciencia:
- Microbiología
- La bioquímica
- Descubrimiento de drogas
Sus antecedentes:
- La lisobactina (katanosina B) es un potente antibiótico eficaz contra las bacterias Gram-positivas como Staphylococcus aureus y Streptococcus pneumoniae.
- Estudios anteriores indicaron que la lisobactina inhibe la biosíntesis del peptidoglicano (PG), pero su mecanismo molecular preciso no estaba claro.
Objetivo del estudio:
- Para aclarar el mecanismo molecular de acción de la lisobactina.
- Determinar con qué sustratos específicos interactúa la lisobactina en las vías de síntesis de la pared celular bacteriana.
Principales métodos:
- Se utilizaron ensayos de inhibición enzimática para estudiar las interacciones entre la lisobactina y los precursores ligados a los lípidos.
- Análisis de los efectos celulares de la unión de la lisobactina en la morfología y viabilidad de las células bacterianas.
Principales resultados:
- La lisobactina forma complejos estables 1:1 con Lipid I, Lipid II y Lipid II ((A) ((WTA), que son sustratos en la biosíntesis del peptidoglicano y el ácido teicoico de pared (WTA).
- La lisobactina se une al extremo reductor de estos precursores ligados a los lípidos, similar a la ramoplanina y la teixobactina.
- A pesar de la unión de varios precursores, el efecto antibacteriano de la lisobactina se debe únicamente a su interacción con el lípido II, causando defectos en el tabique y daño en la envoltura celular.
Conclusiones:
- La lisobactina se dirige al lípido II, un precursor crucial para la construcción de la pared celular bacteriana.
- La unión específica de la lisobactina al lípido II interrumpe la división y la integridad celular bacteriana, lo que lleva a la muerte celular.
- La lisobactina representa un candidato antibiótico prometedor con un mecanismo de acción bien definido dirigido a la biosíntesis esencial de la pared celular.
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