JAC Advance Access published online on September 20, 2007
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkm363
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Induction of multiple antibiotic resistance in Bacteroides fragilis by benzene and benzene-derived active compounds of commonly used analgesics, antiseptics and cleaning agents
1 Greater Los Angeles Veterans Administration Healthcare Systems, University of California, Los Angeles, CA, USA 2 Department of Medicine, University of California, Los Angeles, CA, USA
Received 13 May 2007; returned 30 June 2007; revised 23 August 2007; accepted 24 August 2007
* Correspondence address. Wadsworth Anaerobe Laboratory, Building 304, Room E3-226, GLAVAHCS 691/151J, Los Angeles, CA 90073, USA. Tel: +1-310-268-3404; Fax: +1-310-268-4458; E-mail: lilskil{at}ucla.edu
Objectives: To determine the potential of active compounds (ACs) present in commonly used analgesics/antiseptics and cleaning agents (detergents and disinfectants) to induce multiple antibiotic resistance (MAR) in Bacteroides fragilis.
Methods: B. fragilis ATCC 25285 untreated or pretreated with sublethal concentrations of ACs (n = 25) was grown for 12 h. Susceptibility of cells pre-treated with various ACs to antibiotics and expression of resistance nodulation division family (bmeB) efflux pumps and putative marA-like global activators (PGAs) were measured.
Results: Twelve aromatic ACs containing benzene or its activated derivatives (salicylate, acetaminophen, gingerol, benzoate, phenol, chlorhexidine gluconate, capsaicin, juglone, cinnamaldehyde, benzene, ibuprofen and Triton X-100) induced MAR, which was reduced by carbonyl cyanide m-chlorophenylhydrazone. There was a positive correlation between the predicted degree of benzene activation and the level of induction. Deactivated benzene or non-aromatic ACs were either poor inducers or non-inducers. Efflux pumps bmeB1, 3, 4, 7 and two PGAs bfrA1 and bfrA2 were overexpressed. Expression of bfrA1 or bfrA2 in Escherichia coli caused a >2-fold increase in the MAR and overexpression of acrB, suggesting that they were putative marA orthologues.
Conclusions: These data demonstrate (i) the presence of an MarA-like system(s) in B. fragilis and (ii) the propensity of benzene or its activated derivatives present in pharmaceutical products to induce MAR.
Key Words: cross-resistance , detergents , disinfectants , gene derepression