JAC Advance Access originally published online on June 6, 2006
Journal of Antimicrobial Chemotherapy 2006 58(1):37-46; doi:10.1093/jac/dkl202
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Bacteroides fragilis BmeABC efflux systems additively confer intrinsic antimicrobial resistance
1 Greater Los Angeles Veterans Administration Healthcare Systems Los Angeles, CA, USA 2 Department of Medicine, University of California Los Angeles, CA, USA 3 Department of Oral Microbiology, Matsumoto Dental University Shiojiri, Japan 4 Department of Microbiology, School of Dentistry, Aichi-Gakuin University Nagoya, Japan
Received 16 December 2005; returned 22 February 2006; revised 16 April 2006; accepted 26 April 2006
*Corresponding author. Tel: +1-310-268-3404; Fax: +1-310-268-4458; E-mail: hwexler{at}ucla.edu
Objectives: To determine the prevalence of expression and function(s) of Bacteroides fragilis RND family efflux transport systems (bmeABC1-16).
Methods: The mRNA transcripts of bmeB efflux pump genes were detected in a wild-type strain ADB77 by RT–PCR and expression in different strains was quantified by comparative quantitative real-time RT–PCR. In order to determine independent or additive functions, BmeB 1, 3, 12 and 15 (the first efflux pumps identified) were deleted as singles, doubles, triples or quadruples by the double cross-over technique with pADB242 and antimicrobial susceptibility was assayed by the spiral gradient endpoint technique.
Results: All efflux pumps except bmeB9 were expressed in the wild-type parental strain. Susceptibility to ß-lactams, fluoroquinolones, ethidium bromide, SDS and triclosan was increased in ADB77
bmeB3 (up to 3-fold) and ADB77bmeB1bmeB3bmeB12 (up to 5-fold). Expression of bmeB9 was increased and that of bmeB11 repressed in the latter deletant. A quadruple deletant (ADB77bmeB1bmeB3bmeB12bmeB15) had similar changes as well as a 2-fold increase in expression of bmeB16 and norfloxacin resistance. Expression of bmeB3 was increased in two triple deletants ADB77bmeB1bmeB12bmeB15-type I (2-fold) and ADB77bmeB1bmeB12bmeB15-type II (5.8-fold). Antimicrobial MICs were also increased in the latter deletant; ampicillin (2.6-fold), cefoperazone (3.4-fold), cefoxitin (1.8-fold), tetracycline (36.4-fold), SDS (1.7-fold) and triclosan (2-fold).
Conclusions: These data demonstrate that constitutive bmeB expression is prevalent in B. fragilis. At least seven BmeB efflux pumps are functional in transporting antimicrobials and have overlapping substrate profiles, and at least four confer intrinsic resistance.
Keywords: membrane proteins , co-expression , susceptibility
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. Pumbwe, C. A. Skilbeck, and H. M. Wexler Induction of multiple antibiotic resistance in Bacteroides fragilis by benzene and benzene-derived active compounds of commonly used analgesics, antiseptics and cleaning agents J. Antimicrob. Chemother., December 1, 2007; 60(6): 1288 - 1297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Mima, S. Joshi, M. Gomez-Escalada, and H. P. Schweizer Identification and Characterization of TriABC-OpmH, a Triclosan Efflux Pump of Pseudomonas aeruginosa Requiring Two Membrane Fusion Proteins J. Bacteriol., November 1, 2007; 189(21): 7600 - 7609. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. M. Wexler Bacteroides: the Good, the Bad, and the Nitty-Gritty Clin. Microbiol. Rev., October 1, 2007; 20(4): 593 - 621. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Pumbwe, D. Glass, and H. M. Wexler Efflux Pump Overexpression in Multiple-Antibiotic-Resistant Mutants of Bacteroides fragilis. Antimicrob. Agents Chemother., September 1, 2006; 50(9): 3150 - 3153. [Abstract] [Full Text] [PDF]
|
|