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Artículo
Effect of RecA inactivation and detoxification systems on the evolution of ciprofloxacin resistance in Escherichia coli
Autor/es | Díaz Díaz, S.
Recacha Villamor, Esther García Duque, A. Docobo Pérez, Fernando Blázquez, J. |
Departamento | Universidad de Sevilla. Departamento de Microbiología |
Fecha de publicación | 2022 |
Fecha de depósito | 2022-03-28 |
Publicado en |
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Resumen | 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 ... 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. |
Agencias financiadoras | Instituto de Salud Carlos III Ministerio de Economía y Competitividad (MINECO). España |
Identificador del proyecto | PI17/01501 and PI20-00239
RD16/0016/0001 and REIPI RD16/ 0016/0009 |
Cita | Díaz Díaz, S., Recacha Villamor, E., García Duque, A., Docobo Pérez, F. y Blázquez, J. (2022). Effect of RecA inactivation and detoxification systems on the evolution of ciprofloxacin resistance in Escherichia coli. Journal of Antimicrobial Chemotherapy, 73 (3), 641-645. |
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