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Inhibición covalente de la detección de quórum de las bacterias
Neri Amara1, Roi Mashiach, Dotan Amar
1Department of Chemistry, Ben-Gurion University of the Negev, Be'er Sheva 84105, Israel.
Journal of the American Chemical Society
|July 10, 2009
Resumen
Los investigadores desarrollaron nuevas sondas electrofílicas para inhibir la detección de quórum (QS) en Pseudomonas aeruginosa. Esta modificación covalente del receptor LasR reduce los factores de virulencia y la formación de biopelículas, ofreciendo nuevas estrategias contra las infecciones bacterianas.
Área de la Ciencia:
- Microbiología Microbiología.
- La patogénesis bacteriana es la patogénesis bacteriana.
- Biología Molecular Biología Molecular
Sus antecedentes:
- La detección de quórum (QS) regula la expresión génica bacteriana en función de la densidad de población.
- En Pseudomonas aeruginosa, la QS controla los factores de virulencia y la formación de biopelículas a través del receptor LasR y su ligando.
- P. aeruginosa es un patógeno oportunista que afecta a personas inmunocomprometidas.
Objetivo del estudio:
- Desarrollar una nueva estrategia para inhibir la QS en P. aeruginosa.
- Para apuntar al receptor LasR para la modificación covalente y la interrupción del QS.
Principales métodos:
- Diseño y síntesis de sondas electrófilas dirigidas al bolsillo de unión LasR.
- La unión covalente de las sondas a la cisteína 79 (Cys79) en el receptor LasR.
- Evaluación de la inhibición de la QS, la secreción del factor de virulencia y la formación de biopelículas.
Principales resultados:
- Las sondas electrofílicas inhibieron específicamente la QS mediante la modificación covalente del receptor LasR.
- La inhibición de la QS condujo a una reducción de la secreción de factores de virulencia.
- La modificación covalente dirigida disminuyó la formación de biopelículas.
Conclusiones:
- Primer ejemplo de modificación covalente de un receptor QS.
- Proporciona una nueva herramienta para estudiar el comportamiento del grupo bacteriano.
- Potencial para nuevas estrategias terapéuticas contra la virulencia de P. aeruginosa.
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