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Genome-Wide Analyses of Escherichia coli Gene Expression Responsive to the BaeSR Two-Component Regulatory System

Department of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, Ibaraki,¹ and Core Research Evolutional Science and Technology (CREST), Japan Science and Technology Corporation,² Faculty of Pharmaceutical Science,³ Department of Bacterial Infections, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan⁴

Received 21 July 2004/ Accepted 16 November 2004

The BaeSR two-component regulatory system controls expression of exporter genes conferring drug resistance in Escherichia coli (S. Nagakubo, K. Nishino, T. Hirata, and A. Yamaguchi, J. Bacteriol. 184:4161-4167, 2002; N. Baranova and H. Nikaido, J. Bacteriol. 184:4168-4176, 2002). To understand the whole picture of BaeSR regulation, a DNA microarray analysis of the effect of BaeR overproduction was performed. BaeR overproduction activated 59 genes related to two-component signal transduction, chemotactic responses, flagellar biosynthesis, maltose transport, and multidrug transport, and BaeR overproduction also repressed the expression of the ibpA and ibpB genes. All of the changes in the expression levels were also observed by quantitative real-time reverse transcription-PCR analysis. The expression levels of 15 of the 59 BaeR-activated genes were decreased by deletion of baeSR. Of 11 genes induced by indole (a putative inducer of the BaeSR system), 10 required the BaeSR system for induction. Combination of the expression data sets revealed a BaeR-binding site sequence motif, 5'-TTTTTCTCCATDATTGGC-3' (where D is G, A, or T). Several genes up-regulated by BaeR overproduction, including genes for maltose transport, chemotactic responses, and flagellar biosynthesis, required an intact PhoBR or CreBC two-component regulatory system for up-regulation. These data indicate that there is cross-regulation among the BaeSR, PhoBR, and CreBC two-component regulatory systems. Such a global analysis should reveal the regulatory network of the BaeSR system.

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