Suppression of the SOS response modifies spatiotemporal evolution, post-antibiotic effect, bacterial fitness and biofilm formation in quinolone-resistant Escherichia coli
| Autor: | A García-Duque, Álvaro Pascual, S Diaz-Diaz, Esther Recacha, M. S. Ramos-Guelfo, Jesús Machuca, José-Manuel Rodríguez-Martínez, Jesús Blázquez, Fernando Docobo-Pérez |
|---|---|
| Přispěvatelé: | Instituto de Salud Carlos III, Ministerio de Economía, Industria y Competitividad (España), Red Española de Investigación en Patología Infecciosa, European Commission, Universidad de Sevilla |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Microbiology (medical) medicine.drug_class 030106 microbiology Microbial Sensitivity Tests Drug resistance medicine.disease_cause Microbiology 03 medical and health sciences SOS Response (Genetics) Spatio-Temporal Analysis Antibiotic resistance Drug Resistance Bacterial Escherichia coli medicine Pharmacology (medical) SOS response SOS Response Genetics Pharmacology Chemistry Escherichia coli Proteins Biofilm biochemical phenomena metabolism and nutrition Quinolone Anti-Bacterial Agents DNA-Binding Proteins Ciprofloxacin Rec A Recombinases Infectious Diseases Biofilms Gene Deletion medicine.drug |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 1460-2091 0305-7453 |
| DOI: | 10.1093/jac/dky407 |
| Popis: | [Background] Suppression of the SOS response has been proposed as a therapeutic strategy for potentiating quinolones against susceptible, low-level quinolone-resistant (LLQR) and resistant Enterobacteriaceae. [Objectives] To monitor the functionality of the SOS response in the evolution towards clinical quinolone resistance and study its impact on the evolution of spatiotemporal resistance. [Methods] An isogenic collection of Escherichia coli (derived from the strain ATCC 25922) carrying combinations of chromosomally and plasmid-mediated quinolone resistance mechanisms (including susceptible, LLQR and resistant phenotypes) and exhibiting a spectrum of SOS activity was used. Relevant clinical parameters such as mutation rate, mutant prevention concentration (MPC), bacterial fitness, biofilm formation and post-antibiotic effect (PAE) were evaluated. [Results] Inactivating the SOS response (recA deletion) led to a decrease in mutation rate (∼103 fold) in LLQR compared with WT strains at ciprofloxacin concentrations of 1 mg/L (the EUCAST breakpoint for resistance) and 2.5 mg/L (Cmax), as well as a remarkable delay in the spatiotemporal evolution of quinolone resistance. For all strains, there was an 8-fold decrease in MPC in RecA-deficient strains, with values for LLQR strains decreasing below the Cmax of ciprofloxacin. Inactivation of the SOS response reduced competitive fitness by 33%–50%, biofilm production by 22%–80% and increased the PAE by ∼3–4 h at sub-MIC concentrations of ciprofloxacin. [Conclusions] Our data indicate that suppression of the SOS response affects key bacterial traits and is a promising strategy for reversing and tackling the evolution of antibiotic resistance in E. coli, including low-level and resistant phenotypes at therapeutic quinolone concentrations. This work was supported by the Plan Nacional de I+D+i 2013–2016 and the Instituto de Salud Carlos III (projects PI14/00940 and PI17/01501), Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI; RD16/0016/0001 and REIPI RD16/0016/0009), co‐financed by the European Development Regional Fund ‘A way to achieve Europe’, operative program Intelligent Growth 2014–2020. F. D.-P. is supported by a VPPI-US fellowship from the University of Sevilla. |
| Databáze: | OpenAIRE |
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