Format

Send to

Choose Destination
J Antimicrob Chemother. 2003 Oct;52(4):576-82. Epub 2003 Sep 1.

Beta-lactam resistance modulated by the overexpression of response regulators of two-component signal transduction systems in Escherichia coli.

Author information

1
Department of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047, Japan.

Abstract

OBJECTIVES:

In Escherichia coli, there are 32 open reading frames assumed, on the basis of sequence similarities, to be response regulator genes of two-component signal transduction systems. We cloned all 32 response regulators and examined whether or not response regulator-overexpressing cells confer resistance to beta-lactam antibiotics in E. coli.

METHODS:

E. coli KAM3 (acrB), a drug-hypersusceptible mutant, was used as a host strain for the overproduction of response regulators. MICs were determined by the agar dilution method.

RESULTS:

Thirteen response regulators out of 32 genes, namely baeR, cheY, cpxR, creB, evgA, fimZ, narL, ompR, rcsB, rstA, yedW, yehT and dcuR, conferred increased beta-lactam resistance. Among them, overexpression of baeR, evgA, rcsB and dcuR conferred high-level resistance. The baeR- and evgA-mediated resistance is due to up-regulation of the expression of multidrug exporter genes, acrD and mdtABC for baeR, and yhiUV for evgA, because baeR- and evgA-mediated resistance was completely absent in strains lacking these exporter genes. The fimZ-mediated cefalothin resistance is due to the chromosomal ampC gene, because the ampC deletion strain did not show fimZ-mediated resistance.

CONCLUSIONS:

Two-component signal transduction systems contribute to beta-lactam resistance in E. coli. Multidrug exporters play roles in two-component signal transduction system-mediated beta-lactam resistance.

PMID:
12951338
DOI:
10.1093/jac/dkg406
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center