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Journal of Bacteriology, August 2002, p. 4161-4167, Vol. 184, No. 15
0021-9193/02/$04.00+0     DOI: 10.1128/JB.184.15.4161-4167.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The Putative Response Regulator BaeR Stimulates Multidrug Resistance of Escherichia coli via a Novel Multidrug Exporter System, MdtABC

Satoshi Nagakubo,1,2 Kunihiko Nishino,1,2,3 Takahiro Hirata,1,2,3 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 19 February 2002/ Accepted 29 April 2002

Overproduction of the response regulator BaeR confers resistance to novobiocin and bile salts in a {Delta}acrAB mutant by stimulating drug exporter gene expression. The mdtABC (multidrug transporter ABC, formerly known as yegMNO) genes, which encode a resistance-nodulation-cell division (RND) drug efflux system, are responsible for resistance. The MdtABC system comprises the transmembrane MdtB/MdtC heteromultimer and MdtA membrane fusion protein. MdtAC also confers bile salt, but not novobiocin, resistance. This indicates that the evolution from an MdtC homomultimer to an MdtBC heteromultimer contributed to extend the drug resistance spectrum. A BLAST search suggested that such a heteromultimer-type RND exporter constitutes a unique family among gram-negative organisms.

* 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, August 2002, p. 4161-4167, Vol. 184, No. 15
0021-9193/02/$04.00+0     DOI: 10.1128/JB.184.15.4161-4167.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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