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Antimicrobial Agents and Chemotherapy, May 1999, p. 1085-1090, Vol. 43, No. 5
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Negative Regulation of the Pseudomonas
aeruginosa Outer Membrane Porin OprD Selective for Imipenem
and Basic Amino Acids
Martina M.
Ochs,
Matthew P.
McCusker,
Manjeet
Bains, and
Robert E. W.
Hancock*
Department of Microbiology and Immunology,
University of British Columbia, Vancouver, British Columbia, Canada
V6T 1Z3
Received 10 November 1998/Returned for modification 29 January
1999/Accepted 7 March 1999
Pseudomonas aeruginosa OprD is a specific porin which
facilitates the uptake of basic amino acids and imipenem, a carbapenem antibiotic. Resistance to imipenem due to the loss of OprD is an
important mechanism for the loss of clinical effectiveness. To
investigate the negative regulatory mechanisms influencing oprD expression, a gene upstream of the coregulated
mexEF-oprN efflux operon, designated mexT, was
cloned. The predicted 304-amino-acid mature MexT protein showed strong
homology to LysR-type regulators. When overexpressed it induced the
expression of the mexEF-oprN efflux operon while decreasing
the level of expression of OprD. The use of an
oprD::xylE transcriptional fusion
indicated that it acted by repressing the transcription of
oprD. Salicylate, a weak aromatic acid known to reduce
porin expression and induce low levels of multiple antibiotic
resistance in Escherichia coli, was able to induce imipenem
resistance and reduce the expression of OprD but not multiple
antibiotic resistance or OprN expression in P. aeruginosa.
This was also demonstrated to occur at the level of transcription.
Acetyl salicylate and benzoate, but not catechol, were also able to
reduce the levels of OprD in the P. aeruginosa outer
membranes. These OprD-suppressing compounds increased imipenem resistance even in a mexT-overexpressing and
nfxC mutant backgrounds, suggesting that such resistance is
independent of the MexT repressor and that oprD is
influenced by more than a single mechanism of repression.
*
Corresponding author. Mailing address: Department of
Microbiology and Immunology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada. Phone: (604) 822-2682. Fax: (604) 822-6041. E-mail:
bob{at}cmdr.ubc.ca.
Antimicrobial Agents and Chemotherapy, May 1999, p. 1085-1090, Vol. 43, No. 5
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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