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DCAP: un antibiótico de amplio espectro que se dirige a la membrana citoplasmática de las bacterias
Ye-Jin Eun1, Marie H Foss, Daniela Kiekebusch
1Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Journal of the American Chemical Society
|June 30, 2012
Resumen
Un nuevo antibiótico de amplio espectro, DCAP, se dirige eficazmente a las bacterias latentes y de biofilm al interrumpir sus membranas celulares. Esto ofrece un nuevo tratamiento prometedor para las infecciones persistentes resistentes a los antibióticos tradicionales.
Área de la Ciencia:
- Microbiología Microbiología.
- Enfermedades infecciosas Enfermedades infecciosas.
- Descubrimiento de Drogas Descubrimiento de Drogas
Sus antecedentes:
- Las infecciones persistentes a menudo involucran bacterias de crecimiento lento asociadas con biofilms.
- Los antibióticos convencionales que requieren un rápido crecimiento celular son ineficaces contra estos microbios persistentes.
- Los antibióticos dirigidos a la membrana muestran potencial para combatir las bacterias de crecimiento lento.
Objetivo del estudio:
- Para introducir un nuevo compuesto membrana-activo, DCAP.
- Para evaluar la eficacia del DCAP contra las bacterias persistentes y de biofilm.
- Evaluar el perfil de seguridad del DCAP en células de mamíferos.
Principales métodos:
- Síntesis y caracterización de 2-((3-(3,6-dicloro-9H-carbazol-9-il)-2-hidroxipropilo (amino)-2-(hidroximetil) propano-1,3-diol (DCAP). para el tratamiento de las lesiones cardiovasculares.
- Evaluación del efecto del DCAP en el potencial transmembrana bacteriano y la localización de proteínas de membrana (MinD, FtsA).
- Prueba de la actividad antimicrobiana de DCAP contra bacterias y biofilms privados de nutrientes, y su citotoxicidad en glóbulos rojos y células de mamíferos.
Principales resultados:
- DCAP demostró una actividad antimicrobiana de amplio espectro contra las bacterias Gram-positivas y Gram-negativas.
- DCAP redujo el potencial transmembrana bacteriana y causó la mala localización de las proteínas esenciales de la membrana.
- El DCAP mató efectivamente a las bacterias privadas de nutrientes, esterilizó las biopelículas y exhibió una baja toxicidad celular en mamíferos.
Conclusiones:
- Los compuestos activos de membrana como el DCAP son una estrategia prometedora para el tratamiento de infecciones bacterianas persistentes.
- DCAP representa una nueva molécula pequeña terapéutica con potencial para aplicaciones antimicrobianas de amplio espectro.
- DCAP ofrece una nueva vía para el desarrollo de tratamientos contra las infecciones resistentes a los antibióticos y persistentes.
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