Effect of RecA inactivation and detoxification systems on the evolution of ciprofloxacin resistance in Escherichia coli
| Autor: | S Diaz-Diaz, E Recacha, A García-Duque, F Docobo-Pérez, J Blázquez, A Pascual, J M Rodríguez-Martínez |
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| Přispěvatelé: | Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (España), Comisión Asesora de Investigación Científica y Técnica, CAICYT (España), European Commission, Universidad de Sevilla. Departamento de Microbiología, Ministerio de Economía y Competitividad (MINECO). España |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Pharmacology
Microbiology (medical) Antibiotic resistance Antimicrobials Prevention Bacterial Soft drinks Anti-Bacterial Agents Metabolic detoxication Rec A Recombinases Infectious Diseases Genes Ciprofloxacin Detoxification therapy Sos response (genetics) Escherichia coli Humans Pharmacology (medical) Drug Reactive oxygen species Multi-antibiotic resistance Escherichia coli Infections Fluoroquinolones |
| Zdroj: | idUS. Depósito de Investigación de la Universidad de Sevilla instname |
| Popis: | [Background] Suppression of SOS response and overproduction of reactive oxygen species (ROS) through detoxification system suppression enhance the activity of fluoroquinolones. [Objectives] To evaluate the role of both systems in the evolution of resistance to ciprofloxacin in an isogenic model of Escherichia coli. [Methods] Single-gene deletion mutants of E. coli BW25113 (wild-type) (ΔrecA, ΔkatG, ΔkatE, ΔsodA, ΔsodB), double-gene (ΔrecA-ΔkatG, ΔrecA-ΔkatE, ΔrecA-ΔsodA, ΔrecA-ΔsodB, ΔkatG-ΔkatE, ΔsodB-ΔsodA) and triple-gene (ΔrecA-ΔkatG-ΔkatE) mutants were included. The response to sudden high ciprofloxacin pressure was evaluated by mutant prevention concentration (MPC). The gradual antimicrobial pressure response was evaluated through experimental evolution and antibiotic resistance assays. [Results] For E. coli BW25113 strain, ΔkatE, ΔsodB and ΔsodB/ΔsodA mutants, MPC values were 0.25 mg/L. The ΔkatG, ΔsodA, ΔkatG/katE and ΔrecA mutants showed 2-fold reductions (0.125 mg/L). The ΔkatG/ΔrecA, ΔkatE/ΔrecA, ΔsodA/ΔrecA, ΔsodB/ΔrecA and ΔkatG/ΔkatE/ΔrecA strains showed 4–8-fold reductions (0.03–0.06 mg/L) relative to the wild-type. Gradual antimicrobial pressure increased growth capacity for ΔsodA and ΔsodB and ΔsodB/ΔsodA mutants (no growth in 4 mg/L) compared with the wild-type (no growth in the range of 0.5–2 mg/L). Accordingly, increased growth was observed with the mutants ΔrecA/ΔkatG (no growth in 2 mg/L), ΔrecA/ΔkatE (no growth in 2 mg/L), ΔrecA/ΔsodA (no growth in 0.06 mg/L), ΔrecA/ΔsodB (no growth in 0.25 mg/L) and ΔrecA/ΔkatG/ΔkatE (no growth in 0.5 mg/L) compared with ΔrecA (no growth in the range of 0.002–0.015 mg/L). [Conclusions] After RecA inactivation, gradual exposure to ciprofloxacin reduces the evolution of resistance. After suppression of RecA and detoxification systems, sudden high exposure to ciprofloxacin reduces the evolution of resistance in E. coli. This work was supported by the Plan Nacional de I + D+i 2013‐2016 and the Instituto de Salud Carlos III (projects and PI17/01501 and PI20-00239), 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 European Development Regional Fund ‘A way to achieve Europe’, Operative program Intelligent Growth 2014‐2020. Sara Diaz-Diaz is supported by a PFIS Grant from the Instituto de Salud Carlos III (FI18/00086). |
| Databáze: | OpenAIRE |
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