Akihito Yamaguchi

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Our comprehensive expression cloning studies previously revealed that 20 intrinsic xenobiotic exporter systems are encoded in the Escherichia coli chromosome, but most of them are not expressed under normal conditions. In this study, we investigated the compounds that induce the expression of these xenobiotic exporter genes, and found that indole induces a(More)
AcrB is a principal multidrug efflux transporter in Escherichia coli that cooperates with an outer-membrane channel, TolC, and a membrane-fusion protein, AcrA. Here we describe crystal structures of AcrB with and without substrates. The AcrB-drug complex consists of three protomers, each of which has a different conformation corresponding to one of the(More)
Autophagy is a bulk degradation process in eukaryotic cells and has fundamental roles in cellular homeostasis.The origin and source of autophagosomal membranes are long-standing questions in the field. Using electron microscopy, we show that, in mammalian culture cells, the endoplasmic reticulum (ER) associates with early autophagic structures called(More)
Multidrug-resistant strains of Salmonella are now encountered frequently, and the rates of multidrug resistance have increased considerably in recent years. Here, we report that the two-component regulatory system BaeSR increases multidrug and metal resistance in Salmonella through the induction of drug efflux systems. Screening of random fragments of(More)
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(More)
Sphingosine-1-phosphate (S1P) is a secreted lipid mediator that functions in vascular development; however, it remains unclear how S1P secretion is regulated during embryogenesis. We identified a zebrafish mutant, ko157, that displays cardia bifida (two hearts) resembling that in the S1P receptor-2 mutant. A migration defect of myocardial precursors in the(More)
AcrB and its homologues are the principal multidrug transporters in Gram-negative bacteria and are important in antibiotic drug tolerance. AcrB is a homotrimer that acts as a tripartite complex with the outer membrane channel TolC and the membrane fusion protein AcrA. Minocycline and doxorubicin have been shown to bind to the phenylalanine cluster region of(More)
Drug exporters contribute to the intrinsic drug resistance in many organisms. Although there are at least 20 exporter genes in Escherichia coli, most of them apparently do not confer drug resistance in complex laboratory media except for the AcrAB, EmrE, and MdfA efflux systems. In this study, we comprehensively investigated the growth phase-dependent(More)
Salmonella enterica serovar Typhimurium has at least nine multidrug efflux pumps. Among these pumps, AcrAB is effective in generating drug resistance and has wide substrate specificity. Here we report that indole, bile, and an Escherichia coli conditioned medium induced the AcrAB pump in Salmonella through a specific regulator, RamA. The RamA-binding sites(More)
Overproduction of the response regulator BaeR confers resistance to novobiocin and bile salts in a DeltaacrAB 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(More)