RT Journal Article
T1 Cellular Response to Ciprofloxacin in Low-Level Quinolone-Resistant Escherichia coli.
A1 Machuca, Jesus
A1 Recacha, Esther
A1 Briales, Alejandra
A1 Díaz-de-Alba, Paula
A1 Blazquez, Jesus
A1 Pascual, Alvaro
A1 Rodriguez-Martinez, Jose-Manuel
K1 ciprofloxacin
K1 global response
K1 low-level quinolone resistance
K1 sensitization
K1 survival
K1 transcriptomic
AB Bactericidal activity of quinolones has been related to a combination of DNA fragmentation, reactive oxygen species (ROS) production and programmed cell death (PCD) systems. The underlying molecular systems responsible for reducing bactericidal effect during antimicrobial therapy in low-level quinolone resistance (LLQR) phenotypes need to be clarified. To do this and also define possible new antimicrobial targets, the transcriptome profile of isogenic Escherichia coli harboring quinolone resistance mechanisms in the presence of a clinical relevant concentration of ciprofloxacin was evaluated. A marked differential response to ciprofloxacin of either up- or downregulation was observed in LLQR strains. Multiple genes implicated in ROS modulation (related to the TCA cycle, aerobic respiration and detoxification systems) were upregulated (sdhC up to 63.5-fold) in mutants with LLQR. SOS system components were downregulated (recA up to 30.7-fold). yihE, a protective kinase coding for PCD, was also upregulated (up to 5.2-fold). SdhC inhibition sensitized LLQR phenotypes (up to ΔLog = 2.3 after 24 h). At clinically relevant concentrations of ciprofloxacin, gene expression patterns in critical systems to bacterial survival and mutant development were significantly modified in LLQR phenotypes. Chemical inhibition of SdhC (succinate dehydrogenase) validated modulation of ROS as an interesting target for bacterial sensitization.
PB Frontiers Research Foundation
SN 1664-302X
YR 2017
FD 2017-07-19
LK http://hdl.handle.net/10668/11468
UL http://hdl.handle.net/10668/11468
LA en
NO Machuca J, Recacha E, Briales A, Díaz-de-Alba P, Blazquez J, Pascual Á, et al. Cellular Response to Ciprofloxacin in Low-Level Quinolone-Resistant Escherichia coli. Front Microbiol. 2017 Jul 19;8:1370.
DS RISalud
RD Apr 7, 2025