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La acción combinada de los sistemas reguladores genera heteroresistencia a la colistina
Jacob E Choby1,2,3, Emily K Crispell1,2,3, Muqing Ma1,4
1Emory Antibiotic Resistance Center, Atlanta, GA, USA.
bioRxiv : the preprint server for biology
|August 20, 2025
Resumen
Un factor sigma, σE, genera heterogeneidad en la resistencia a la colistina dentro de las poblaciones de Enterobacter cloacae. Esta heterogeneidad, combinada con la actividad del sistema PhoPQ, es crucial para la supervivencia frente a los antibióticos de colistina.
Área de la Ciencia:
- Microbiología
- La genética
- Biología molecular
Sus antecedentes:
- La heteroresistencia implica una pequeña subpoblación resistente dentro de una mayor susceptible.
- La heteroresistencia a la colistina en Enterobacter cloacae es un desafío clínico significativo.
- Los mecanismos que generan heterogeneidad fenotípica en la resistencia a la colistina siguen siendo poco conocidos.
Objetivo del estudio:
- Identificar los mecanismos moleculares responsables de generar la heterogeneidad de la población en la resistencia a la colistina.
- Esclarecer la interacción entre los mecanismos de heterogeneidad y resistencia en Enterobacter cloacae.
Principales métodos:
- Utilizó una pantalla de mutagénesis basada en transposones para identificar genes involucrados en la heterogeneidad de la resistencia a la colistina.
- Utilizó experimentos de seguimiento de células individuales para observar la dinámica de la población bajo exposición a la colistina.
- Se investigó el papel del sistema de dos componentes PhoPQ junto con los factores de heterogeneidad identificados.
Principales resultados:
- Identificó el factor sigma σE como el generador clave de la heterogeneidad en la resistencia a la colistina.
- σE es activo en una pequeña subpoblación (1%) al inicio, y estas células sobreviven a la exposición a la colistina.
- La resistencia a la colistina requiere tanto heterogeneidad mediada por σE como modificación del lípido A mediada por PhoPQ.
Conclusiones:
- La heteroresistencia a la colistina surge de la acción coordinada de sistemas reguladores distintos.
- Un "generador de heterogeneidad" (σE) y un "generador de resistencia" (PhoPQ) son ambos necesarios para la heteroresistencia de la colistina.
- Este estudio propone un nuevo paradigma para comprender la generación de heteroresistencia a los antibióticos.
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