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Journal of Bacteriology, March 2003, p. 1851-1856, Vol. 185, No. 6
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.6.1851-1856.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Comprehensive Studies of Drug Resistance Mediated by Overexpression of Response Regulators of Two-Component Signal Transduction Systems in Escherichia coli

Hidetada Hirakawa,1,2 Kunihiko Nishino,1,2,3 Takahiro Hirata,1,3 and Akihito Yamaguchi1,2,3*

Department of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, Ibaraki,1 CREST, Japan Science and Technology Corporation, Osaka 567-0047,3 Faculty of Pharmaceutical Science, Osaka University, Suita, Osaka 565-0871, Japan2

Received 16 September 2002/ Accepted 18 December 2002

In Escherichia coli, there are 32 open reading frames (ORFs) that are assumed to be response regulator genes of two-component signal transduction systems on the basis of sequence similarities. We cloned all of these 32 ORFs into a multicopy expression vector and investigated whether or not they confer drug resistance via control of drug resistance determinants. Fifteen of these ORFs, i.e., baeR, citB, cpxR, evgA, fimZ, kdpE, narL, narP, ompR, rcsB, rstA, torR, yedW, yehT, and dcuR, conferred increased single- or multidrug resistance. Two-thirds of them conferred deoxycholate resistance. Five of them, i.e., evgA, baeR, ompR, cpxR, and rcsB, modulated the expression of several drug exporter genes. The drug resistance mediated by evgA, baeR, and cpxR could be assigned to drug exporters by using drug exporter gene knockout strains.

* Corresponding author. Mailing address: Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki-shi, Osaka 567-0047, Japan. Phone: 81-6-6879-8545. Fax: 81-6-6879-8549. E-mail: akihito{at}sanken.osaka-u.ac.jp.

Journal of Bacteriology, March 2003, p. 1851-1856, Vol. 185, No. 6
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.6.1851-1856.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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