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Mecanismos de persistencia bacteriana durante el estrés y la exposición a antibióticos

Alexander Harms¹, Etienne Maisonneuve¹, Kenn Gerdes²

¹Center of Excellence for Bacterial Stress Response and Persistence (BASP), Department of Biology, Ole Maaløes Vej 5, DK-2200 Copenhagen, Denmark.

Science (New York, N.Y.)

|December 17, 2016

Resumen

Las células bacterianas persistentes sobreviven a los antibióticos al entrar en estado de latencia, un factor clave en el fracaso del tratamiento. Comprender sus variados mecanismos moleculares es crucial para superar la resistencia a los antibióticos.

Área de la Ciencia:

Microbiología
Biología molecular
Descubrimiento de drogas

Sus antecedentes:

Las células bacterianas persistentes son células latentes que sobreviven al tratamiento con antibióticos, lo que lleva al fracaso del tratamiento y a las infecciones recurrentes.
La formación de persistentes está influenciada por procesos estocásticos y señales ambientales, a menudo reguladas por el segundo mensajero (p) pGpp.
Los módulos de toxina-antitoxina contribuyen significativamente a la formación de células persistentes en varios sistemas bacterianos.

Objetivo del estudio:

Revisar el conocimiento actual de la formación de células bacterianas persistentes.
Para resaltar los avances recientes en los mecanismos moleculares subyacentes a la generación de células persistentes.
Explorar las fuentes de la heterogeneidad fisiológica dentro de las subpoblaciones persistentes.

Principales métodos:

Revisión de la literatura de las investigaciones actuales sobre las células bacterianas persistentes.
Análisis de las vías moleculares implicadas en la formación de persistentes, incluida la señalización (p) ppGpp y los sistemas toxina-antitoxina.
Síntesis de los hallazgos sobre la heterogeneidad de las subpoblaciones persistentes y sus mecanismos de tolerancia.

Principales resultados:

Las células persistentes evitan los antibióticos a través de la latencia fisiológica, lo que contribuye al fracaso del tratamiento.
Diversas vías moleculares, incluida la señalización (p) ppGpp y los módulos toxina-antitoxina, regulan la formación de persistentes.
La diversidad molecular impulsa la heterogeneidad fisiológica, confiriendo tolerancia a múltiples fármacos y múltiples tensiones a las células persistentes.

Conclusiones:

Las células bacterianas persistentes representan un desafío significativo en el tratamiento de enfermedades infecciosas.
La comprensión de las bases moleculares de la formación y la heterogeneidad persistentes es esencial para el desarrollo de nuevas estrategias terapéuticas.
Dirigirse a los mecanismos celulares persistentes puede ofrecer una forma de mejorar la eficacia de los antibióticos y combatir las infecciones recurrentes.

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