Suppression of the SOS response modifies spatiotemporal evolution, post-antibiotic effect, bacterial fitness and biofilm formation in quinolone-resistant Escherichia coli.
J Antimicrob Chemother
; 74(1): 66-73, 2019 01 01.
Article
em En
| MEDLINE
| ID: mdl-30329046
ABSTRACT
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 (â¼103 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 â¼3-4 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Resposta SOS em Genética
/
Biofilmes
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Farmacorresistência Bacteriana
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Escherichia coli
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Antibacterianos
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article