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Drug Resist Updat ; 75: 101087, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38678745

RESUMEN

In recent years, new evidence has shown that the SOS response plays an important role in the response to antimicrobials, with involvement in the generation of clinical resistance. Here we evaluate the impact of heterogeneous expression of the SOS response in clinical isolates of Escherichia coli on response to the fluoroquinolone, ciprofloxacin. In silico analysis of whole genome sequencing data showed remarkable sequence conservation of the SOS response regulators, RecA and LexA. Despite the genetic homogeneity, our results revealed a marked differential heterogeneity in SOS response activation, both at population and single-cell level, among clinical isolates of E. coli in the presence of subinhibitory concentrations of ciprofloxacin. Four main stages of SOS response activation were identified and correlated with cell filamentation. Interestingly, there was a correlation between clinical isolates with higher expression of the SOS response and further progression to resistance. This heterogeneity in response to DNA damage repair (mediated by the SOS response) and induced by antimicrobial agents could be a new factor with implications for bacterial evolution and survival contributing to the generation of antimicrobial resistance.


Asunto(s)
Antibacterianos , Ciprofloxacina , Proteínas de Escherichia coli , Escherichia coli , Pruebas de Sensibilidad Microbiana , Rec A Recombinasas , Respuesta SOS en Genética , Respuesta SOS en Genética/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Ciprofloxacina/farmacología , Humanos , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Antibacterianos/farmacología , Rec A Recombinasas/genética , Rec A Recombinasas/metabolismo , Farmacorresistencia Bacteriana/genética , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Daño del ADN/efectos de los fármacos , Secuenciación Completa del Genoma , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/tratamiento farmacológico , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Adaptación Fisiológica , Reparación del ADN/efectos de los fármacos , Proteínas de Unión al ADN
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