ABSTRACT
The aim of this work was to determine whether diazepam could induce the multiple antibiotic resistance (Mar) phenotype in Klebsiella pneumoniae and Escherichia coli strains. The Mar phenotype is characterized by decreased susceptibility to multiple antibiotics due to the loss of porins and/or increased expression of active efflux systems. The effect of subinhibitory concentrations of diazepam on the susceptibility of different antimicrobial agents, outer-membrane protein expression and norfloxacin intracellular accumulation was studied. The results revealed that diazepam concentrations equal or twice adult dosage induced the same Mar phenotype as two well known E. coli marRAB inducers, sodium salicylate and sodium benzoate. Susceptibility to norfloxacin in a K. pneumoniae clinical isolate and E. coli strain Ag100 decreased due to enhanced active efflux and loss of porin expression. A decreased susceptibility to chloramphenicol, tetracycline, nalidixic acid and beta-lactam antibiotics was also observed. In conclusion, like sodium salicylate or sodium benzoate, diazepam may induce the Mar phenotype.
Subject(s)
Bacterial Outer Membrane Proteins/biosynthesis , Diazepam/pharmacology , Drug Resistance, Multiple, Bacterial/drug effects , Escherichia coli/drug effects , Gene Expression Regulation, Bacterial/drug effects , Klebsiella pneumoniae/drug effects , Norfloxacin/metabolism , Anti-Bacterial Agents/pharmacology , Biological Transport, Active/drug effects , Cytoplasm/chemistry , Enzyme Activators/pharmacology , Escherichia coli/genetics , Escherichia coli/metabolism , Klebsiella pneumoniae/genetics , Klebsiella pneumoniae/metabolism , Microbial Sensitivity Tests , Norfloxacin/pharmacology , Porins/biosynthesis , Sodium Benzoate/pharmacology , Sodium Salicylate/pharmacologyABSTRACT
The effect of salicylate, a marRAB inducer, on the resistance to beta-lactams was characterized in an AmpC beta-lactamase hyperproducer Morganella morganii clinical isolate (the M1 strain). Results were compared with those of the effect of salicylate in a wild-type M. morganii strain. Salicylate induced a decreased susceptibility to nalidixic acid, norfloxacin and tetracycline and simultaneously increased the susceptibility to beta-lactams apparently due to the repression of AmpC beta-lactamase synthesis in the M1 strain. Likewise, salicylate only repressed 46 kDa outer membrane protein expression in the wild-type strain, since the clinical isolate M1 did not express it.
