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Un nuevo antibiótico mata selectivamente a los patógenos gramnegativos

Yu Imai1, Kirsten J Meyer1, Akira Iinishi1

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Los investigadores descubrieron la darobactina, un nuevo antibiótico eficaz contra los patógenos Gram negativos resistentes a los medicamentos. Este compuesto, derivado de simbiontes bacterianos, se dirige a las proteínas esenciales de la membrana externa, ofreciendo una nueva vía terapéutica prometedora.

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Área de la Ciencia:

  • Microbiología
  • Descubrimiento de drogas
  • La bioquímica

Sus antecedentes:

  • El aumento de los patógenos Gram negativos resistentes a los medicamentos requiere nuevos antibióticos.
  • Las bacterias gramnegativas poseen una barrera de permeabilidad restrictiva que impide la penetración de antibióticos.
  • El desarrollo de nuevas clases de antibióticos contra las bacterias gramnegativas se ha estancado desde la década de 1960.

Objetivo del estudio:

  • Identificar nuevos compuestos antibióticos eficaces contra los patógenos Gram negativos resistentes a los medicamentos.
  • Explorar los simbiontes bacterianos como fuente de nuevos agentes antimicrobianos.
  • Para caracterizar un antibiótico recién descubierto, la darobactina.

Principales métodos:

  • Evaluación de la actividad antibiótica de los aislados bacterianos de Photorhabdus.
  • Investigando la base genética y la biosíntesis de la darobactina.
  • Evaluación de la eficacia de la darobactina in vitro y en modelos de infección animal.
  • Analizar el mecanismo de resistencia mediante la identificación de mutantes resistentes.

Principales resultados:

  • Descubrimiento de darobactina, un nuevo antibiótico sintetizado por ribosoma.
  • Darobactin exhibe una potente actividad contra los patógenos gramnegativos in vitro e in vivo.
  • La darobactina posee una estructura única con dos anillos fusionados formados post-traducionalmente.
  • La resistencia a la darobactina surge de mutaciones en BamA, un translocador esencial de proteínas de la membrana externa.

Conclusiones:

  • Los simbiontes animales bacterianos albergan candidatos prometedores a los antibióticos.
  • Darobactin representa un agente terapéutico potencial para el tratamiento de infecciones bacterianas Gram negativas.
  • Dirigirse a BamA ofrece una estrategia viable para desarrollar nuevos antibióticos contra patógenos desafiantes.