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Changsheng Wu¹, Zhuo Shang¹, Christophe Lemetre¹

¹Laboratory of Genetically Encoded Small Molecules , The Rockefeller University , New York , New York 10065 , United States.

Journal of the American Chemical Society

|February 9, 2019

Resumen

Los investigadores descubrieron nuevos antibióticos dependientes del calcio, los cadasidos, eficaces contra las bacterias resistentes. Estos nuevos lipopéptidos interrumpen la biosíntesis de la pared celular, ofreciendo una vía prometedora para combatir la resistencia a los antibióticos.

Área de la Ciencia:

Microbiología
La bioquímica
Descubrimiento de drogas

Sus antecedentes:

La resistencia a los antibióticos es una amenaza creciente para la salud mundial.
Los antibióticos dependientes del calcio son una clase de lipopéptidos con diversos mecanismos contra los patógenos resistentes.
Las sintetasas de péptidos no ribosómicos (NRPS) son clave para su ensamblaje.

Objetivo del estudio:

Identificar y caracterizar nuevos antibióticos dependientes del calcio.
Explorar nuevas estrategias para el descubrimiento de antibióticos activos contra patógenos resistentes.
Investigar las bases genéticas de la producción de cadáveres.

Principales métodos:

Se usó la secuenciación del dominio de adenilación de NRPS (AD) para identificar grupos de genes.
Se examinó el ADN metagenómico para recuperar el clúster de genes biosintéticos.
Se empleó la expresión heteróloga para producir y analizar los compuestos.

Principales resultados:

El clúster de genes de CDE fue identificado y clonado a partir de un metagenoma del suelo.
Se produjeron dos nuevos lipopéptidos ácidos, los cadasidos A y B.
Las cadasidas exhiben una estructura única e inhiben los patógenos Gram-positivos multirresistentes al interrumpir la biosíntesis de la pared celular.
Los grupos de genes de tipo cadássico son frecuentes en suelos ricos en calcio.

Conclusiones:

Las cadasidas representan una nueva subfamilia de antibióticos dependientes del calcio.
Estos compuestos muestran potencial para el tratamiento de infecciones causadas por bacterias multirresistentes.
Los hallazgos ponen de relieve la utilidad de la secuenciación de NRPS para el descubrimiento de antibióticos y sugieren un vínculo ambiental entre la biosíntesis de cadácidos y los niveles de carbonato de calcio.

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