Open AccessSublethal ciprofloxacin treatment leads to resistance via antioxidant systems in P roteus mirabilis
Author(s) -
Aiassa Virginia,
Barnes Ana I.,
Smania Andrea M.,
Albesa Inés
Publication year - 2012
Publication title -
fems microbiology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.899
H-Index - 151
eISSN - 1574-6968
pISSN - 0378-1097
DOI - 10.1111/j.1574-6968.2011.02453.x
Subject(s) - proteus mirabilis , ciprofloxacin , microbiology and biotechnology , proteus , antioxidant , biology , chemistry , pseudomonas aeruginosa , bacteria , antibiotics , biochemistry , genetics , escherichia coli , gene
This study investigates new aspects of the possible role of antioxidant defenses in the mechanisms of resistance to ciprofloxacin in P roteus mirabilis . Four ciprofloxacin‐resistant variants ( CRV s), selected in vitro by repeated cultures in a sub‐minimum inhibitory concentration ( MIC ) concentration of ciprofloxacin , attained different levels of antibiotic resistance and high Ferric reducing antioxidant power, with 10 −6 frequencies. However, no mutations occurred in positions 83 or 87 of gyrA , 464 or 466 of gyrB , or 78, 80 or 84 of parC , suggesting that resistance took place without these typical mutations in DNA gyrase or topoisomerase IV . Assays with ciprofloxacin and the pump inhibitor carbonyl cyanide m ‐chlorophenylhydrazone showed that in addition to the antioxidant mechanisms, the influx/efflux mechanism also contributed to the increase in the resistance to ciprofloxacin in one CRV . Moreover, lipid oxidation to malondialdehyde and protein oxidation to carbonyls and advanced oxidation protein products were higher in sensitive than in the resistant strains, as a new factor involved in the mechanisms of resistance in P . mirabilis . The oxidative stress cross‐resistance to telluride in CRV s enhanced the role of the antioxidants in the ciprofloxacin resistance of P . mirabilis , which was reinforced during the assays of reduction of susceptibility to ciprofloxacin by glutathione and ascorbic acid.