Journal Article

β-Lactam resistance modulated by the overexpression of response regulators of two-component signal transduction systems in <i>Escherichia coli</i>

Hidetada Hirakawa, Kunihiko Nishino, Junko Yamada, Takahiro Hirata and Akihito Yamaguchi

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 52, issue 4, pages 576-582
Published in print October 2003 | ISSN: 0305-7453
Published online October 2003 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dkg406
β-Lactam resistance modulated by the overexpression of response regulators of two-component signal transduction systems in Escherichia coli

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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 β-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 β-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 β-lactam resistance in E. coli. Multidrug exporters play roles in two-component signal transduction system-mediated β-lactam resistance.

Keywords: Keywords: β-lactams, multidrug exporters, drug resistance, E. coli

Journal Article.  3817 words. 

Subjects: Medical Oncology ; Critical Care

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