CONCLUSION

CHAPTER IV

ACKNOWLEDGEMENTS

I wish to express my sincere gratitude to Dr. Ryutaro Utsumi, Professor of Faculty of Agriculture, Kinki University, for his valuable advice, stimulating discussion, critical review throughout the work, and especially for his superb guidance into the fascinating world of molecular biology. I wish to thank Dr. Shigeru Shigeoka and Dr. Yukio Kawamura, Professors of Faculty of Agriculture, Kinki University, for reading the entire text in its original form.

Special thanks are due to Dr. Hirotada Mori and Dr. Taku Oshima of Nara Institute of Science and Technology for the microarray analysis and computer search for consensus sequences. I am greatly indebted to Dr. Akira Ishihama of Nippon Institute for Biological Science for the supply of RNA polymerase, antibodies and plasmids, and also for the critical reading of Chapter II, and also to Dr. Nobuhisa Masuda of Sankyo Pharmaceuticals and Dr. George M. Church of Harvard Medical School for their generous supply of strains and plasmids. I also wish to thank Dr. Kaneyoshi Yamamoto and Dr. Hiroyuki Tanabe of Kinki University for kind suggestions and valuable discussions throughout the work.

Many thanks are due to Tadashi Okada, Junichi Ito, Ryo Demizu, Shohei Kobira, Nozomi Ishida and Tomoko Sawai, for their helpful collaborations. Thanks are also due to all the past and present members of the laboratory of Biochemistry in the Faculty of Agriculture, Kinki University, for their kind cooperation and for creating such a friendly and cheerful atmosphere.

Finally, very special thanks are forwarded to my family for their continuous support and cooperation, without which this work was never possible.

REFERENCES

Aiba, H. (1983). Autoregulation of the Escherichia coli crp gene: CRP is a transcriptional repressor of its own gene. Cell 32, 141-149.

Albright, L. M., Huala, E. & Aus bel, E. M. (1989). Prokaryotic signal transduction mediated by sensor and regulator protein pairs. Annu Rev Genet23, 11-36.

Alexander, D. M. & S t John, A. C. (1994). Characterization of the carbon starvation-inducible and stationary phase-inducible gene slp encoding an outer membrane lipoprotein in Escherichia coli.Mol Microbiol11, 1059-1071.

Aono, R., Aibe, K., Inoue, A. & Horikoshi, K. (1991). Preparation of organic solvent tolerant mutants from Escherichia coli K-12. Agric Biol Chem 55, 1935-1938.

Aono, R., Tsukagoshi, N. & Y amamoto, M. (1998). Involvement of outer membrane protein TolC, a possible member of the mar-sox regulon, in maintenance and improvement of organic solvent tolerance of Escherichia coli K-12. J Bacterio l 180, 938-944.

Arico, B., V. Scarlato, D. M. Monack, S. Falkow, and R. Rappuoli. (1991). Structural and genetic analysis of the bvg locus in Bordetella species. Mol. Micr obiol. 5, 2481-2491.

Arnqvist A., Olsén, A. & Normark, S. (1994). ^S-dependent growth-phase induction of the csgBA promoter in Escherichia coli can be achieved in vivo by ⁷⁰ in the absence of the nucleoid-associated protein H-NS. Mol Microbiol 13, 1021-1032.

Baranova, N. & Nikaido, H. (2002). The BaeSR two-component regulatory system activates transcription of the yegMNOB (mdtABCD) transporter gene cluster in Escherichia coli and increases its resistance to novobiocin and deoxycholate. J

Bacteriol 184, 4168-4176.

Bock, A. & Gr oss, R. (2002). The unorthodox histidine kinases BvgS and EvgS are responsive to the oxidation status of a quinone electron carrier. Eur J Biochem 269, 3479-3484

Castanie-Cornet, M. P ., Penfound, T . A., Smith, D., Elliott, J. F . & Foster , J. W . (1999). Control of acid resistance in Escherichia coli. J Bacteriol181, 3525-3535.

Castanie-Cornet, M. P. & Foster J. W. (2001).Escherichia coli acid resistance: cAMP receptor protein and a 20 bp cis-acting sequence control pH and stationary phase expression of the gadA and gadBC glutamate decarboxylase genes. Microbiology 147, 709-715.

Casadaban, M. J. (1976). Transposition and fusion of lac genes to selected promoters in Escherichia coli using bacteriophage lambda and Mu. J Mol Biol 104, 541-555.

Castelli, M. E., García Véscovi, E. & Soncini, F. C. (2000). The phosphatase activity is the target for Mg²⁺ regulation of the sensor protein PhoQ in Salmonella. J. Biol. Chem.

275,22948-22954.

DeBiase, D., T ramonti, A., Bossa, F ., & V isca P . (1999). The response to stationary-phase stress conditions in Escherichia coli: role and regulation of the glutamic acid decarboxylase system. Mol Microbiol 40, 465-475.

Edgar, R. & Bibi, E. (1997). MdfA, an Escherichia coli multidrug resistance protein with an extraordinarily broad spectrum of drug recognition. J Bacteriol179, 2274-2280.

Edgar, R. & Bibi, E. (1999). A single membrane-embedded negative charge is critical for recognizing positively charged drugs by the Escherichia coli multidrug resistance protein MdfA. EMBO J18, 822-832.

Fralick, J. A. (1996). Evidence that TolC is required for functioning of the Mar/AcrAB efflux pump of Escherichia coli.J Bacteriol178, 5803-5805.

García Véscovi, E., Soncini, F . C. & Gr oisman, E. A. (1996). Mg²⁺ as and extracellular signal: environmental regulation of Salmonella virulence. Cell 84, 165-174.

García Véscovi, E., A yala, Y . M., Di Cera, E. & Gr oisman, E. A. (1997).

Characterization of the bacterial sensor protein PhoQ. Evidence for distinct binding sites for Mg²⁺ and Ca²⁺. J Biol Chem 272, 1440-1443.

Georgellis, D., Kwon, O. & Lin, E. C. (2001). Quinones as the redox signal for the arc two-component systems of bacteria. Science 292, 2314-2316.

Gong, S., R ichard, H. & Foster , J. W. (2003). YjdE (AdiC) is the arginine:agmatine antiporter essential for arginine-dependent acid resistance in Escherichia co li. J Bacteriol 185, 4402-4409.

Groisman, E. A. (2001). The pleiotropic two-component regulatory system PhoP-PhoQ.

J Bacteriol 183, 1835-1842.

Gunn, J. S. & Miller , S. I. (1996). PhoP-PhoQ activates transcription of pmrAB, encoding a two-component regulatory system involved in Salmonella typhimurium antimicrobial peptide resistance. J Bacteriol 178, 685-6864.

Guo, L., Lim, K. B., Gunn, J. S., Bainbrid ge, B., Darvean, R. P ., Hackett, M. &

Miller S. I. (1997). Regulation of lipidA modifications by Salmonella typhimurium virulence genes phoP-phoQ. Science276, 250-253.

Hersh, B. M., Farooq, F. T., Barstad, D. N., Blankenshorn, D. L. & Slonc zewski, J.

L. (1996). A gluatamate-dependent acid resistance gene in Escherichia coli. J Bacteriol 178, 3978-3981.

Jack, D. L., Storms, M. L., Tchieu, J. H., Paulsen, I. T. & Saier M. H. Jr (2000). A broad-specificity multidrug efflux pump requiring a pair of homologous SMR-type proteins. J Bacteriol 182, 2311-2313.

Jishage, M. & Ishihama, A. (1997). Variation in RNA polymerase sigma subunit composition within different stocks of Escherichia coli W3110. J Bacterio l 179, 959-963.

Kajitani, M. & Ishihama, A. (1983). Determination of the promoter strength in the mixed transcription system: promoters of lactose, tryptophan and ribosomal protein L10 operons from Escherichia coli. Nucleic Acids Res 11, 671-686.

Kato, A., T anabe, H. & Utsumi, R. (1999). Molecular characterization of the PhoP-PhoQ two-component system in Escherichia coli K-12: Identification of extracellular Mg²⁺-responsive promoters. J Bacteriol181, 5516-5520.

Kato, A., Ohnishi, H., Yamamoto, K., Furuta, E., Tanabe, H. & Utsumi, R. (2000).

Transcription of emrKY is regulated by the EvgA-EvgS two-component system in Escherichia coli K-12. Biosci Biotechnol Biochem64, 1203-1209.

Kato, A. (2000). Studies on signal transduction of environmental adaptation. PhD thesis.

Kinki University, Department of Bioscience and Biotechnology.

Kato, A., T . Latifi, & Gr oisman, E. A. (2003). Closing the loop: The PmrA/PmrB two-component system negatively controls expression of its posttranscriptional activator PmrD. Proc Natl Acad Sci USA 100, 4706-4711.

Kox, L. F., Wosten, M. M. & Gr oisman, E. A. (2000). A small protein that mediates the activation of a two-component system by another two-component system. EMBO J 19, 1861-1872.

Lee, A., Mao, W., Warren, M. S., Mistry, A., Hoshino, K., Okumura, R., Ishida, H,

& Lomovskaya, O. (2000). Interplay between efflux pumps may provide either additive or multiplicative effects on drug resistance. J Bacteriol182, 3142-3150.

Lesley, J. A. & Waldburger, C. D. (2003). Repression of Escherichia coli PhoP-PhoQ signaling by acetate reveals a regulatory role of acetyl coenzyme A. J Bacteriol 185, 2463-2570.

Loewen, P. C. & Hengge-Ar onis, R. (1994). The role of sigma factor sigma S (KatF) in bacterial global regulation. Annu Rev Microbiol48, 53-80.

Loewen, P. C., Hu, B., S trutinsky, J. & Sparling, R. (1998). Regulation in the rpoS regulon of Escherichia coli. Can J Microbiol 44, 707-717.

Lomovskaya, O. & Watkins, W. (2002). Inhibition of efflux pumps as novel approach to combat drug resistance in bacteria. In: Microbiol Multidrug Efflux. Edited by Paulsen, I. & Lewis, K. Wymondham, UK, Horizon Scientific Press, 201-231.

Lomovskaya, O., Lewis, K. & Matin, A. (1995). EmrA is a negative regulator for the Escherichia coli multidrug resistance pump EmrAB. J Bacteriol 177, 2328-2334.

Ma, D., Cook, D. N., Alberti, M., Po n, N. G., Nikaido, H. & Hearst, J. E. (1993).

Molecular cloning and characterization of acrA and acrE genes of Escherichia coli. J Bacteriol175, 6299-6313.

Ma, Z., Gong, S., Rich ard, H., T ucker, D. L., Conw ay, T. & Foster , J. W . (2003). GadE (YhiE) activates glutamate decarboxylase-dependent acid resistance in Escherichia coli K-12. Mol Microbiol49, 1309-1320.

Makinoshima H., Nishimura, A. & Ishihama, A. (2002). Fractionation of Escherichia coli cell populations at different stages during growth transition to stationary phase. Mol Microbiol 43, 269-279.

Martin, R. G ., Gillette, W . K., Rhee, S. & Rosner , J. L. (1999). Structural requirements for marbox function in transcriptional activation of mar/sox/rob regulon promoters in Escherichia coli: sequence, orientation and spatial relationship to the core promoter. Mol Microbiol 34, 431-441.

Masuda, N. & Chur ch, G. M. (2002). Escherichia coli gene expression responsive to levels of the response regulator EvgA. J Bacteriol 184, 6225-6234.

Masuda, N. & Chur ch, G. M. (2003). Regulatory network of acid resistance genes in Escherichia coli.Mol Microbiol 48, 699-712

McLeod, S. M., Xu, J. & Johnson, R. C. (2000). Coactivation of the RpoS-dependent proP P2 promoter by Fis and cyclic AMP receptor protein. J Bacteriol 182, 4180-4187.

Mellies, J., W ise, A. & V illarejo, M. (1995). Two different Escherichia coli proP promoters respond to osmotic and growth phase signals. J Bacteriol 177, 144-151.

Miller, J. H. (1972) . Experiments in molecular genetics. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N. Y.

Miller, J. H. (1992). A Short Course in Bacterial Genetics. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N. Y.

Minagawa, S., Ogasaw ara, H., Kato, A., Yamamoto, K., Eguchi, Y ., Osh ima, T., Mori, H., Ishihama, A. & Utsumi, R. (2003). Identification and molecular characterization of the Mg²⁺-stimulon of Escherichia coli. J Bacteriol 185, 3696-3702.

Mizuno, T. (1997). Compilation of all genes encoding two-component phosphotranfer signal transducers in the genome of Escherichia coli. DNA Res 4, 161-168.

Nagakubo, S., Nishino, K., Hirata, T. & Yamaguchi, A. (2002). The putative response

regulator BaeR stimulates multidrug resistance of Escherich ia coli via a novel multidrug exporter system, MdtABC. J Bacteriol184, 4161-4167.

Nishino, K. & Y amguchi, A. (2001a). Overexpression of the response regulator evgA of the two-component signal transduction system modulates multidrug resistance conferred by multidrug resistance transporters. J Bacteriol 183, 1455-1458.

Nishino, K. & Yamaguchi, A. (2001b). Analysis of a complete library of putative drug transporter genes in Escherichia coli. J Bacteriol 183, 5803-5812.

Nishino, K. & Yamaguchi, A. (2002). EvgA of the two-component signal transduction system modulates production of the YhiUV multidrug transporter in Escherichia coli. J Bacteriol184, 2319-2323.

Nishino, K., Inazumi, Y. & Yamaguchi, A. (2003). Global analysis of genes regulated by EvgA of the two-component regulatory system in Escherichia coli. J Bacteriol 185, 2667-2672.

Oshima, T., Wada, C., Kawagoe, Y., Ara, T., Maeda, M., Masuda, Y., Hiraga, S. &

Mori, H. (2002a). Genome-wide analysis of deoxyadenosine methyltransferase- mediated control of gene expression in Escherichia coli. Mol Microbiol45, 673-695.

Oshima, T., Aiba, H., Masuda, Y., Kanaya, S., Sugiura, M., Wanner, B. L., Mori, H.

& Mizuno, T. (2002b). Transcriptome analysis of all two-component regulatory system mutants of Escherichia coli K-12. Mol Microbiol46, 281-291.

Paulsen, I. T., Sliwinski, M. K. & Saier, M. H. Jr. (1998). Microbial genome analyses:

global comparisons of transport capabilities based on phylogenies, bioenergetics and substrate specificities. J Mol Biol 277, 573-593.

Perraud, A.-L., Weiss, V. & Gross, R. (1999). Signaling pathways in two-component

Preston, A., E. Maxim, E. T oland, E. J. Pi shko, E. T, Harvill, M. Car off, & D. J.

Maskell. (2003). Bordetella bronchiseptica PagP is a Bvg-regulated lipid A palmitoyl transferase that is required for persistent colonization of the mouse respiratory tract. Mol.

Microbiol. 48: 725-736.

Soncini, F. C. & Gr oisman, E. A. (1996). Two-component regulatory systems can interact to process multiple environmental signals. J Bacteriol 178, 6796-6801.

Stibitz, S. & Yang, M.-S. (1991). Subcellular localization and immunological detection of proteins encoded by the vir locus of Bordetella pertussis. J Bacteriol 173, 4288-4296.

Sulavik, M. C., Housew eart, C., Cramer , C., Jiwani, N., Murgol o, N., Gr eene, J., DiDomenico, B., Show, K. J., Miller, G. H., Hare, R. & Shimer, G.(2001). Antibiotic susceptibility profiles of Escherichia coli strains lacking multidrug efflux pump genes.

Antimicrob Agents Chemother45, 1126-1136.

Tanabe, H., Yamasaki, K., Kato, A., Yoshioka, S. & Utsumi, R.(1998). Identification of the promoter region and the transcriptional regulatory sequence of the evgAS operon of Escherichia coli.Biosci Biotechnol Biochem62, 286-270.

Tatsuno, I., Nagano, K., T aguchi, K., Ron g, L., Mori, H. & Sasakaw a, C. (2003).

Increased adherence to Caco-2 cells caused by disruption of the yhiE and yhiF genes in Enterohemorrhagic Escherichia coli O157:H7. Infect Immun 71, 2598-2606.

Tsukagoshi, N. & Aono, R. (2000). Entry into and release of solvents by Escherichia coli in an organic aqueous two-liquid-phase system and substrate specificity of the AcrAB-TolC solvent extruding pump. J Bacteriol 182, 4803-4810.

Tucker, D. L., Tucker, N. & Conway, T. (2002). Gene expression profiling of the pH response in Escherichia coli. J Bacteriol 184, 6551-6558.

Utsumi, R., Katayama, S., Taniguchi, M., Horie, T., Ikeda, M., Igaki, S., Nakagawa, H., Miwa, A., Tanabe, H. & Noda, M. (1994). Newly identified genes involved in the signal transduction of Escherichia coli K-12. Gene140, 73-77.

Utsumi, R. (2002). Bacterial signal transduction systems for environmental adaptation and their inhibitors. Microbes and Environment 17, 1-5.

Van Velkinburgh, J. C. & Gunn, J. S. (1999). PhoP-PhoQ-regulated loci are required for enhanced bile resistance in Salmonella spp. Infect. Immun. 67, 1614-1622.

Waldburger, C. D. & Sauer , R. T . (1996). Signal detection by the PhoQ sensor-transmitter. J. Biol. Chem.271, 26630-26636.

Xu, J. & Johnson, R. C. (1995). Fis activates the RpoS-dependent stationary phase expression of proP in Escherichia coli. J Bacteriol 177, 5222-5231.

Xu, J. & Johnson, R. C. (1997). Activation of RpoS-dependent proP P2 transcription by Fis protein in vitro. J Mol Biol270, 346-359.

Yamamoto, K., Ogasaw ara, H., Fujita, N., Utsumi, R., & Ishihama, A. (2002).

Novel mode of transcription regulation of divergently overlapping promoters by PhoP, the regulator of two-component system sensing external magnesium availability. Mol Microbiol45, 423-438.