ABSTRACT The complete sequencing of bacterial genomes has revealed a large number drug transporter genes. In Escherichia coli , there are 37 open reading frames (ORFs) assumed to be genes on the basis sequence similarities, although transport capabilities most them have not been established yet. We cloned all putative in E. and investigated their resistance phenotypes using an drug-sensitive mutant as host. cells transformed with plasmid carrying one 20 ORFs, i.e., fsr mdfA yceE yceL bcr...

Sphingosine-1-phosphate (S1P) is a secreted lipid mediator that functions in vascular development; however, it remains unclear how S1P secretion regulated during embryogenesis. We identified zebrafish mutant, ko157 , displays cardia bifida (two hearts) resembling the receptor-2 mutant. A migration defect of myocardial precursors mutant due to mutation multipass transmembrane protein, Spns2, and can be rescued by injection. show export from cells requires Spns2. spns2 expressed extraembryonic...

ABSTRACT In the Escherichia coli genome, five putative open reading frame (ORF) clusters, mdlAB , ybjYZ yddA yojHI and yhiH have been assumed to be possible genes for ABC drug efflux transporters (I. T. Paulsen, M. K. Sliwinski, H. Saier, Jr., J. Mol. Biol. 277:573–592, 1998). We cloned all of these ORFs in multicopy plasmids investigated resistance drug-supersensitive host cells lacking constitutive multidrug transporter acrAB . Among them, only gave significant erythromycin significantly...

Summary Our comprehensive expression cloning studies previously revealed that 20 intrinsic xenobiotic exporter systems are encoded in the Escherichia coli chromosome, but most of them not expressed under normal conditions. In this study, we investigated compounds induce these genes, and found indole induces a variety genes including acrD , acrE cusB emrK mdtA mdtE yceL . Indole treatment E. cells confers rhodamine 6G SDS resistance through induction mdtEF gene respectively. The by is...

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 resistance-nodulation-cell division (RND) efflux system, are responsible for resistance. MdtABC system comprises transmembrane MdtB/MdtC heteromultimer MdtA membrane fusion protein. MdtAC also salt, but not novobiocin, This indicates that evolution...

Salmonella enterica serovar Typhimurium has at least nine multidrug efflux pumps. Among these pumps, AcrAB is effective in generating drug resistance and wide substrate specificity. Here we report that indole, bile, an Escherichia coli conditioned medium induced the pump through a specific regulator, RamA. The RamA-binding sites were located upstream regions of acrAB tolC. RamA was required for indole induction acrAB. Other regulators such as MarA, SoxS, Rob, SdiA, AcrR did not contribute to...

Multidrug-resistant strains of Salmonella are now encountered frequently, and the rates multidrug resistance have increased considerably in recent years. Here, we report that two-component regulatory system BaeSR increases metal through induction drug efflux systems. Screening random fragments genomic DNA for ability to increase beta-lactam enterica led isolation a plasmid containing baeR, which codes response regulator BaeSR. When overexpressed, baeR significantly delta acrB strain...

Sphingosine-1-phosphate (S1P), a sphingolipid metabolite that is produced inside the cells, regulates variety of physiological and pathological responses via S1P receptors (S1P1–5). Signal transduction between cells consists three steps; synthesis signaling molecules, their export to extracellular space recognition by receptors. An concentration gradient essential for migration various cell types express receptors, such as lymphocytes, pre-osteoclasts, cancer endothelial cells. To maintain...

Tetracycline uptake into inverted membrane vesicles from Tn10-bearing Escherichia coli cells required divalent cations. The degree of the stimulation tetracycline by various cations showed following decreasing order: Co2+ greater than Mn2+ Mg2+ Cd2+ Ca2+. This order is consistent with increasing dissociation constants for metal chelate complexes tetracycline. Hill rate cation concentrations were one. These observations strongly suggested that a 1:1 complex and was transported resistance...

FTY720 is a novel immunomodulating drug that can be phosphorylated inside cells; its form, FTY720-P, binds to sphingosine 1-phosphate (S1P) receptor, S1P(1), and inhibits lymphocyte egress into the circulating blood. Although importance of pharmacological action has been well recognized, little known about how FTY720-P released from cells after phosphorylation cells. Previously, we showed zebrafish Spns2 act as an S1P exporter essential for heart formation. Here, demonstrate human SPNS2...

AcrB is the major multidrug exporter in Escherichia coli. Although several substrate-entrances have been identified, specificity of these various transport paths remains unclear. Here we present evidence for a substrate channel (channel 3) from central cavity trimer, which connected directly to deep pocket without first passing switch-loop and proximal . Planar aromatic cations, such as ethidium, prefer 3 channels 1 2. The efflux through increases by targeted mutations not competition with...

ABSTRACT The major mechanism of resistance to fluoroquinolones for Pseudomonas aeruginosa is the modification type II topoisomerases (DNA gyrase and topoisomerase IV). We examined mutations in quinolone-resistance-determining regions (QRDR) gyrA, gyrB, parC , parE genes recent clinical isolates. There were 150 isolates with reduced susceptibilities levofloxacin 127 ciprofloxacin among 513 collected during 1998 1999 Japan. Sequencing results predicted replacement an amino acid QRDR DNA (GyrA...

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

Sphingosine 1-phosphate (S1P) is accumulated in platelets and released on stimulation by thrombin or Ca(2+). Thrombin-stimulated S1P release was inhibited staurosporin, whereas Ca(2+)-stimulated not. When the platelet plasma membrane permeabilized with streptolysin O (SLO), leaked out cytosol markers, granular markers remained platelets. The SLO-induced leakage required BSA, probably for solubilization of medium. These results indicate that localized inner leaflet its a carrier-mediated...

The transposon Tn10-encoded tetracycline resistance protein functions as a metal-tetracycline/H+ antiporter (Yamaguchi, A., Udagawa, T., and Sawai, T. (1990) J. Biol. Chem. 265, 4809-4813). Ser65-Asp66 dipeptide is conserved in all known proteins an important target for site-directed mutagenesis. When Asp66 was replaced by Asn, the transport activity completely lost, whereas when it Glu, reduced to 10% of wild-type level, indicating that negative charge at position 66 essential transport....

ABSTRACT Overexpression of the EvgA regulator two-component signal transduction system was previously found to modulate multidrug resistance Escherichia coli by increasing efflux drugs (K. Nishino and A. Yamaguchi, J. Bacteriol. 183:1455-1458, 2001). Here we present data showing that contributes through increased expression transporter yhiUV gene.

AcrAB exports some beta-lactam antibiotics in the periplasm out of cells via an outer-membrane channel, TolC. It has been reported that eight drug transporters Escherichia coli cooperate with In this study, roles exporters E. resistance were examined. We found five resistance-nodulation-cell division-type confer antibiotic resistance, while no other any even when they

ABSTRACT 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 H. Nikaido, 4168-4176, 2002). To understand the whole picture regulation, a DNA microarray analysis effect BaeR overproduction was performed. activated 59 related to signal transduction, chemotactic responses, flagellar biosynthesis, maltose transport,...