Phẫu thuật điều trị động kinh thùy thái dương

Molecular Characterization of the Mechanisms of Adhesion of Helicobacter pylon': a Model of Environmental Regulation of Bacterial Attachment Mario Huesca Contreras A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy, Graduate Department of Molecular and Medical Genetics University of Toronto Copyright by Mario Huesca Contreras 1999 National Library Bibliothkque nationale du Canada Acquisitions and Bibliographic Services Acquisitions et services bibiiographiques 395 Wellington Street OttawaON KtAON4 395, rue Wellington Ottawa ON K I A ON4 Canada Canada Your Ne V o l r s d U m m O u r lVe Notfa fd(BfBlICB The author has granted a nonexclusive licence allowing the National Library of Canada to reproduce, loan, distribute or sell copies of this thesis in microform, paper or electronic formats L'auteur a accorde une licence non exclusive permettant a la Bibliotheque nationale du Canada de reproduire, preter, distribuer ou vendre des copies de cette these sous la forme de microfiche/film, de reproduction sur papier ou sur format electronique The author retains ownership of the copyright in this thesis Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission L'auteur conserve la propriete du droit d'auteur qui protege cette these Ni la these ni des extraits substantiels de celle-ci ne doivent &re imprimes ou autrement reproduits sans son autorisation Molecular Characterization of the Mechanisms of Adhesion of Helicobacterpylori: a Model of Environmentzl Regulation of Bacterial Attachment Mario Huesca Contreras Degree of Doctor of Philosophy 1999 Department of Molecular and Medical Genetics, University of Toronto Incubation of acid-treated Helicobacter pylori with lipid receptors in vitro, showed a change in the pattern of binding usually observed a t neutral pH The major lipid species recognized at pH 2.0 and pH 2.5, which is the pH of the stomach lumen, were sulfatides (sulfogalactosylceramide, SGC), one of the most abundant glycolipids of the human stomach mucus The suspicion that the SGC binding of H pylori was a stress induced response is supported by the finding of a similar change in binding specificity when the organisms were briefly exposed to heat-shock treatment Following stress stimulus, the change in glycolipid binding specificity was prevented by the inclusion of protein synthesis inhibitors, or by incubation of acid-treated H pylori with anti-Hsp antibodies Expression of Hsps in surface extracts of H pylori, and bacterial surface reactivity with anti-Hsp antibodies, correlated with the change in glycolipid binding specificity Previous experiments in our laboratory which showed binding of heat shock proteins members of the Hsp7O family to sulfatide, led t h e investigation of the roIe of the H pylori Hsp7O (DnaK) in the acid stress induction of SGC binding The H pylori DnaK gene was cloned and sequenced, and its level of transcription and translation following acid stress determined A single transcript, of approximately 1.9 kb in size, not detected under non stress conditions, was induced in H pylori, exposed to 420C and pH 2.5 Analysis of metabolically labeled proteins, induced by incubation of H pylori at acidic conditions (pH 2.51, showed a typical post-stress pattern of protein synthesis Two major electrophoretic bands induced by these conditions corresponded to the heat shock proteins Hsp6O (GroEL) and DnaK Preliminary characterization of PE-binding adhesins which correspond t o a second phase of H.pylori colonization, that is the attachment to the epithelial cells surface and the entry into intercellular spaces, identified several proteins including the enzymes catalase and urease, as we11 as a 62 kDa protein with an N-terminal sequence similar to an internal sequence present in bovine serum albumin (BSA) and TB66, a protein identified in Mycobactert urn tuberculosis iii -1 dedicate this Thesis to Silvia, Eddie and Mariana: "Thisis our accomplishment" -To my sister Yolanda and and m y brother Leon Acknowledgments I am especially thankful to my supervisor Dr Cliff Lingwood for his support and encouragement, and to the people of the laboratory: Beth, Anita, Daniel, Desheng, Myl, Aye Aye, Prateek and Shirley To Dr Paul Hoffman for his advice and good discussions and for his contribution with the electron microscopy studies; to Avery Goodwin for the primer extension experiments To Dr Phil Sherman and Dr Julie Silver for their support and advice To Sergio Borgia for his contribution to the H pylori overlay experiments Dissemination of work arising from this thesis Chapters and of this Thesis were published as follows: -Huesca, M., S Borgia, P H o h a n and C A Lingwood 1996 "AcidicpH changes receptor binding of Helicobacter pylori: a binary adhesion model in which surface heatshock (stress) proteins mediate sulfatide recognition in gastric colonization".Infect hnmun 64:2643-2648 -Huesca, M., A Goodwin, A Bhagwansingh, P H o h a n and C A Lingwood 1998 "Characterizationof an acidic pH-inducible stress protein (hsp7O) &om Helicobacter pylori, a putative sulfatide binding adhesin" Infect Immun 66:4061-4067 Table of Contents Page Title page i Abstract ii Acknowledgments v Dissemination of work arising from this thesis vi Table of Contents v11 List of Tables x List of Figures xi Chapter 1: Introduction The gastric pathogen Helicobacter pylory Pathogenesis of the infection with H pylori .7 Inflammatory response -Type I and type I1 strains -Bacterial adhesion -The pathogenicity island of H pylori type I strains -Other pro-inflammatory factors -10 T cell responses .11 A n t i X pylori antibodies and autoimmunity 12 H.pylori enzymes as virulence factors -16 Stomach association of H pylori .16 The gastric mucosa 16 pH of the stomach Composition of the stomach mucus gel 21 -Stomachcolonization by Helicobacter pylori 25 Adaptive features for colonization of the stomach 25 vii Mechanisms of survival of H pylori 35 The stomach as a natural barrier against micro-organisms .35 pH homeostasis -35 Induction of synthesis of stress protein by acid shock 37 Heat shock proteins -37 -Classification of heat shock proteins 37 The 70 kD heat shock proteins (Hsp7O ) 38 The 60 kDa heat shock proteins (HspGO) 40 Protein folding in bacteria a The Hsp9O and other small molecular weight Hsp 53 Regulation of the stress response 54 Stress response induced by acid shock 56 Surface expression of Heat shock proteins 60 Sulfated sphingolipids as receptors for heat shock proteins 65 Adhesion of Helicobacter pylori 71 Bacterial receptors .71 Glycosphingolipids -72 Bacterial adhesins -.-.* * .* - -78' Receptors and adhesins of Helicobacter pylori 79 Identification of potential lipid-receptors by thin layer chromatography (TLC)overlay assay -93 Aflinity purification of lipid-binding ligands 93 Chapter 2: Rationale and objectives 95 Chapter 3: Stress Response Alters the receptor binding specificity of Helicobacter pylori Surface heat-shock proteins mediate sulfatide recognition 98 Summary -99 viii Introduction 99 Material and Methods -101 Results 105 Discussion 124 Chapter 4: Characterizationof an acidic pH-inducible (hsp70) stress protein from Helicobacter pylori, a putative sulfatide binding adhesin 132 Summary 133 Introduction 134 Material and Methods 135 Results 140 Discussion -159 Chapter 5: Characterization of Phospatydilethanolamine (PE)binding adhesins from Helicobacter pylori 163 Summary 164 Introduction 165 Material and methods 166 Results 170 Discussion 184 Chapter 6: Significance and hture directions -187 Chapter 7: References -198 21 Liberek K., Skowrya D, Zylicz M., Johnson C, Georgopoulos C 1991 The Escherichia coli DnaK chaperone, the 70 kDa heat shock protein eukaryotic equivalent, changes conformation upon ATP hydrolysis, thus triggering its dissociation from a bound target protein J Biol Chem 266: 14-491-1496 Lindberg, A A, J.E.Brown, N Striimberg, M Westling-Ryd, J E Schultz and K.-A Karlsson 1987 Identification of the carbohydrate receptor for Shiga toxin produced by Shigella dysenteriae type 1.J Biol Chem 262~1779-1785 Lindquist, S 1986 The heat-shock response Annu Rev Biochem 55:1151-1191 Lingwood, C k 1984 The production of glycolipid affinity matrices by use of heterobifunctional crosslinking agents J Lipid Res 25:1010-1012 Lingwood, C A 1985 Protein-glycolipid interactions: Binding of specific germ cell proteins to sulfatoxygalactosyl-acylalkylglycerol,the major glycolipid of mammalian spermatogenic cells Can J Biochem Cell Biol63: 1077-1085 Lingwood, C A, H Law, A Pellizzari, P Sherman and B.Drumm 1989 A gastric glycerolipid as a receptor for Campylobacter pylori Lancet ii 238-241 Lingwood, C A, P.A Q u b ,S Wilarnsky, k Nutikka, H Ruhnke and R B Miller 1990a Common sulfoglycolipid receptor for mycoplasma involved in infertility Biol Reprod 43:694-697 Lingwood, C A, S Schramayr and P.Quinn.1990 The male germ cell specific sulfogalactoglycerolipid is recognized and degraded by mycoplasma which induce male infertility J Cell Physiol 142:170-176 Lingwood, C A 1991 Glycolipids as receptors Advances Lipid Res 1~39-55 Lingwood, C A, D E Woods and H C Krivan 1991 Helicobacter pylori: Its lipid receptors and adhesin VI International Workshop on Campylobacter Helicobacter and related organisms 4:s 123 Lingwood, C A, M Cheng,H Krivan and D.E.Woods 1991 Glycolipid receptor binding specificity of exoenzyme S from Pseudornonas aeruginosa Biochem Biophys Res Commun 175:1076-1081 Lingwood, C A., MaHuesca and A Kuksis 1992 The glycerolipid receptor for Helicobacter pylori (and exoenzyme S) is phosphatidylethanolamine Infect Immun 60:2470-2474 Lingwood, C k 1992 Bacterial cell adhesins/glycolipid receptors Curr Opin Struct Biol2:693-700 Lingwood, C A,D Woods and H Krivan 1992c M-selectins and their glycolipid receptors: Common microbial cell adhesin molecules for the attachment of many microorganisms to host cell surface receptors ASM, New Orleans, May 26-30, Abst.B-409 ASM Annual Meeting Lingwood, C k 1993a H.pylori adhesins and receptors 209-222 In: S Goodwin and B W (eds), Helicobacter pylori: biology and clinical practice CRC Press, Boca Raton, Fla Lingwood, C A, G Was*, H Han and M Huesca 199313 Receptor affinity purification of a lipid-binding adhesin from Helicobacter pylori Infect Immun 61:2474-2478 Lingwood, C A and A Nutikka 1994 A novel chemical procedure for the selective removal of nonreducing terminal N-acetyl residues from glycolipids Anal Biochem 217:119-123 Lingwood C A 1998 Oligosaccharide receptors for bacteria:a view to a kill (in press) Locht, C.,P.Berth, F D Menozzi and G Renadd 1993 The filamentous haemagglutinin, a multifaceted adhesion produced by virulent Bordetella spp Mol Microbiol9:653-660 Loomis, W F and S A Wheeler 1982 Chromatin-associated heat shock proteins in Dictyostelium Dev Biol 90: 412-418 Lu, D., B Boyd and C k Lingwood (In preparation) The expression and characterization of a putative adhesin B from H.Influenzae Macchia, G, A Massone, D Burroni, A Covacci, S Censini and R Rappuoli 1993 The Hsp6O protein from H pylori, structure and immune response in patients with gastroduodenal diseases Mol Microb 9:645-652 Mai, U E., G-I Perez-Perez, J B men, S M Wahl, M J Blaser and P D Smith 1994 Surface proteins from Helicobacterpylori exhibit chemotactic activity for human leukocytes and are present in gastric mucosa J Exp Med 175:517-525 Mamelak, D and C Lingwood 1997 Expression and sulfogalactolipid binding of the recombinant testis-specific cognate heat shock protein 70 Glycoconj J 14:715-722 Maniatis, T., E Fritsch and J Sambrook 1982 A laboratory manual In: Cold Spring Harbor Laboratory Cold Spring Harbor Marck, C 1988 "DNA Strider": a 'C' program for fast analysis of DNA and protein sequences on the Apple Macintosh family of computers Nuc Acid Res 173:1829-1836 Marcus, Dm1976 Applications of immunological techniques to the study of glycosphingolipids 233-245 in : Glycolipid Methodology American Oil Chemists Society Press Marshall, B J and J R.Warren 1984 Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration Lancet 1: 13111315 Marshall, B J., L J Barrett, C Prakash, IE W.McCallum and R 1; Guerrant 1990 Urea protects Helicobacter (Campylobacter) pylori from the bactericidal effect of acid Gastroenterology 99:697-702 M a r s h a , B J., D B McGechie, P A Rogers and R J Glancy 1985 Pyloric campylobacter infection and gastroduodenal disease Med J Aust 142:439-444 Martin, J.,k L Horwich and F U Hart1 1992 Prevention of protein denaturation under heat stress by the chaperonine HspGO Science 258: 995998 Matin A, E Zychksky, M, Keyhan and G Sachs 1996 Capacity of Helicobacter pylori to generate ionic gradients a t low pH is similarto that of bacteria which grow under strongly acidic conditions Infect Irnmun 64:1434-1436 McGowan, C., T L Cover and M J Blaser 1994 The proton pump inhibitor Oemprazole inhibits acid survival of Helicobacter pylori by a urease-independent mechanism Gastroenterology 107:738-743 McGowan, C.C.,T.L Cover and M Blaser 1996 Helicobacter pylori and gastric acid: biological and therapeutic implications Gastroenterology 110:926-938 McGowan, C C., T L Cover and M.Blaser 1997 Analysis of FIFOATPase from Helicobacter pylori Infect Immun 65: 2640-2647 Mecsas J., Rouviere P Em,Erickson J.W., Donohue T J., Gross C A 1993 The activity of GE, a n Escherichia coli heat inducible o factor, is modulated by expression of outer membrane proteins Genes Dev 7: 26182628 I Melchers K T Weizenegger, A, Buhmann, W.Steinhilber, G Sachs and K P Schafer 1996 Cloning and membrane topology of a P -ATPase fkom Helicobacter pylori J B i d Chem 271:446-457 Mentis, A,C C Blackwell, D M, Weir, C.Spiliadis,A Dailianas and N Skandalis 1991 ABO blood group,secretor status and detection of Helicobacter pylori among patients with gastric o r duodenal ulcers Epidemiol Infect 106:221-229 Meyer-Rosberg K, D R Scott, Dm Rex, K Melchers and Sachs G 1996 The effect of environmental pH on the proton motive force of Helicobacter pylori Gastroenterology 11 1: 886-900 Miller, Dm,S Brough andl Al-Harbi 1992 Characterization and cellular distribution of human spermatozoa1 heat shock proteins H u m Reprod 7:637-645 Miller-Podraza, H., M k MiIh, J Bergstrom and K A Karlsson 1996 Recognition of glycoconjugates by Helicobacter pylori: an apparently high-affinity binding of human polyglycosylceramides, a second sialic acidbased specificity Glycoconj J 13:453-460 Miller-Podraza,H., M, A Milh, S Tenebreg and K Karbson 1997 Binding of Helicobacter pylori to silaic acid-containing glycolipids of variuos origins separated on thin-layer chromatograms Infect Immun 54:24802482 Minton, K W., P Karmin, G M Hahn and GP Minton 1982 Nonspecific stabilization of stress-susceptible proteins by stress-resistant proteins: a model for the biological role of heat shock proteins Proc Natl Acad Sci (USA) 79:7107-7111 Miyazaki, I., EL Gaedigk, M F.Hui, R K Cheung, J Morkowski, R V Rajotte and H M Dosch 1994 Cloning of human and rat p69, a candidate autoimmune target in Type I diabetes Biochim Biophys Acta 1227:lOl-104 Moran, A 1996 Pathogenic properties of Helicobacter pylori Scand J Gastroenteroi 31:22-31 Moran A, M M, Prendergast and B J Appelmelk 1996 Molecular mimicry of host structures by bacterial lypopolysaccharides and its contribution to disease FEMS Immunol Med Microb l6:IOs- 115 Morimoto, Re1993 Cells in stress: transcriptional activation of heat shock genes Science 259:1409-1410 Morimoto, R and G Santoro 1998 Stress-inducible responses and heat shock proteins New pharmacologic targets for cytoprotection Nature Bioch 16:833-838 Morris, A, and G Nicholson 1987.Ingestion of Campylobacter pyloridis causes gastritis and raised gastric pH Am J Gastroenterol 82:192199 Momhauser R C.,H Wang ,G C.Iilynn and R P Zuiderweg 1995 The peptide binding domain of the chaperone protein Hsc7O has an unusual secondary structure topology Biochemistry 34: 6261-6266 Multhoff, G., C ktzler, L.Jennen ,J Schmidt,J Ellwart and R Issels 1997 Heat shock protein 72 on tumor cells A recognition structure for natural killer cells J Lmmunol 158: 4341-4350 Muriddo, H 1979 Early intermediates in bacteriophage Lambda prohead assembly Virology 96: 341-367 Munro S and H R.B Pelham 1986 An Hsp7O-like protein in the ER: Identity with the 78 kD glucose-regulated protein and immunoglobulin heavy chain binding protein Cell 46: 291-300 Namavar F., M.Sparrius, E Veerman, B.Appelmelk and C Vandenbroucke-Grauls.1998 Neutrophil-activating protein mediates adhesion of Helicobacter pylori to sulfated carbohydrates on highmolecular-weight salivary mucin Infect Immun 66:444-447 Natomi, H.,T.Saitoh, K Sugano,M Iwamori, M Fukayama and Y Nagai 1993 Systematic analysis of glycosphingolipids in the human gastrointestinal tract: enrichment of sulfatides with hydroxylated longerchain fatty acids in the gastric and duodenal mucosa Lipids 28:737-742 Neidhardt, F C., TC k VanBogelen and V Vaughn 1984 The genetics and regulation of heat-shock proteins Annu Rev Genet 18:295-329 Nomura, A, G.N Sternmermann, P.-H Chyou,I Kato, G PerezPerez and M J Blaser 1991 Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii N Engi J Med 325:11321136 O'garra A and Murphy K 1994 Role of cytokines in determining Tlymphocyte function Curr Opin Immunol 6:458-466 O'Toole, P W., L Janzon, P Doig, J.Huang, M Kostrzynska and T J Trust 1995 The putative neuraminyllactose-bindinghemagglutinin HpaA of Helicobacter pylori CCUG 17874 is a lipoprotein J Bacterial 17'26049-6057 Oberhube, G., k Kranz, C Dejaco, B Dragosics, I Mosberger, W Mayr and T Radasziewicz 1997 Blood group ~ e w i and s ~ ABH expression in gastric mucosa:lack of inter-relation with Helicobacter pylori colonisation and occurrence of gastric MALT lymphoma Gut 41~37-42 Odenbreit S, Be W i e h d and R Haas 1996 Cloning and genetic characterization of Helicobacter pylori catalase and construction of a catalase-deficient mutant strain.J Bacterial 178:6960-6967 Oh KJ., H Zhan ,C Cui ,E Hideg ,R.J Collier and W.L Hubbell 1996 Organization of diphteria toxin T domain in bilayers: a site-directed spin labeling study Science 273 : 810-812 Oldenburg, Be, R J.Diepersloot and J B Hoekstra 1996 High seroprevalence of Helicobacter pylori in diabetes mellitus patients Dig Dis Sci 41: 458-461 Oriol, jR, J Le Pendu and R Mollicone 1986 Genetics of ABO, H, Lewis, X and related antigens Vox Sang 51:161-171 Padan, Em, D Zilberstein and S Schuldiner 1981 pH homeostasis in bacteria Biochim Biophys Acta 650:151-166 Panaretou, B and P Piper 1992 The plasma membrane of yeast acquires a novel heat shock protein (Hsp30) and displays a decline in pumping ATPase levels in response to both heat shock and the entry to stationary phase Eur J Biochem 206:635-640 Parsonnet, J., G Friedman, D Vandersteen, Y Chang, J Vogelman, N.Orentreich and R Sibley 1991 He1 icobacter py Lori idection and the risk of gastric carcinoma N Engl J Med 325:llZ7-1131 Parsons, L M., It.J Limberger and M Shayegani 1997 Alterations in levels of DnaK and GroEL result in diminished survival and adherence of stressed Haemophilus ducreyi Infect Immun 65:2413-2419 Paruchuri, Dm IL,H S Seifert, R S Ajioka and K.-A ICarlsson 1990 Identification and characterization of a Neisseria gonorrhoeae gene encoding a glycolipid-binding adhesin Proc Natl Acad Sci USA 87:333-337 Pettit, R Id,M J.Filiatrauit and E S Martin 1996 Alteration of gonococcal protein expression in acidic culture Infect Immun 64:10391042 Phadnis S H., Parlow M H., Levy RZ,Liver D., Caulkins C M., Connors J B., Dunn B E 1996 Surface localization of Helicobacter pylori urease and heat shock protein homolog requires bacterial autolysis Infect Imrnun 64: 905-912 Phillips,G J and J Silhavy 1990 Heat shock proteins DnaK and GroEL facilitate export of lacZ hybrid proteins in E coli Nature (London): 344: 882-884 Procecco,M., E Buratti, k Tollunasini, G Torre and T Not 1997 High risk of Helicobacter pylori infection associated with cow's milk antibodies in young diabetics Acta Paediatr 86:700-703 Prodro~ou,C, S M Roe, R O'Brien, J.E Ladbury, P W Piper and L H Pearl 1997 Identification and structural characterization of the ATP/ADP-binding site in the Hsp9O molecular chaperone Cell 90:65-75 Quigley, EmM and L ATurnberg 1987 pH of the microclimate lining human gastric and duodenal mucosa in vivo Gastroenterology 92=1876-1884 Rathbone, B J., WyattW J.I., Wyatt, B W Worsley, S E.Shires, L K Trejdosiewicz, R V Heatley, M S Losowsky, 1986 Systemic and local antibody responses to gastric Campylobacter pyloridis in non-ulcer dyspepsia Gut 27:642-647 Ratnakar, P.,S Rao and A Catanzaro 1996 Isolation and characterization of a 70 kDa protein fkom Mycobacterium aviurn Microb Pathog 21:471-486 Raulston, J E., C.H Davis, DmH Schmiel, M W Morgan and P B Wyrick 1993 Molecular characterization and outer membrane association of a Chlamydia trachomatis protein related to the Hsp7O family of proteins J Biol Chem 268:23139-23147 Retzlnff C., Y.Yamamoto, S Okubo,P.S Hoffman, H Friedman and T.W.Klein 1996 Legionella pneumophila heat shock protein induced increase of interleukin l b mRNA involves protein kinase C signalling in macrophages Immunology 156:ll96-I206 Rollarson, T P., J Stone and J M Rhodes 1984 Spiral organisms in endoscopic biopsies of the human stomach J Clin Path01 37:23-26 Rosenberg Me 1979 Regulatory sequences involved in the promotion and termination of RNA transcription Annu Rev Genet 13:319-353 Itouviere P.E., A De las Penas ,C Z Lu ,K E Rudd and C A Gross 1995 rpoE, the gene encoding the second heat shock sigma factor oE, in Escherichia coli EMBO J 14: 1032-1042 Sachs, G., N Zeng and C.Prinz.1997 Physiology of isolated gastric endocrine cells Annu Rev Physiol 59: 243-256 Sadelain,MeW.J., H Qin, J Lanzon and B Singh 1990 Prevention of type diabetes in NOD mice by adjuvant immunotherapy Diabetes 3%583-599 Saito, M and k Rosenberg 1985.Influence of monovalent cation transport on anabolism of glycosphingolipids in cultured human fibroblasts Biochem 24:30543059 Saitoh, T.,H Natomi,W.Zhao, R Okuzumi, EL Sugano,M.Iwamori and Y.Nagai 1991.Identification of glycolipid receptors for Helicobacter pylori by TLC-immunostaining FEBS Lett 282:385-387 Saitoh, T., K Sugano, HeNatomi, W Zhao, K Okuzumi, M Iwamori and Y Yazaki 1992 Glycosphingolipid receptors i n human gastric mucosa for Helicobacter pylori Eur J Gastroenterol Hepatol 4:S49-S53 Sakagami, T.,M Dixon, J O'Rourke, R Howlett, F Alderuccio, J Vella, T Shimoyama and A Lee 1996.Atrophic gastric changes in both Helicobacter felis and Helicobacter pylori infected mice are host dependent and separate fkom antral gastritis Gut 39:639-648 Sanger, F., S Nicklen and k Coulson 1977.DNA sequencing with chain terminating inhibitors Proc Natl Acad Sci USA 745463-5468 Scheibel,T., S Neuhofen, T.Weikl, C Mayr, J.Reinstein, P D Vogel and J Buchner 1997.ATP-binding properties of human Hsp9O J Biol Chem 272:18608-18613 Schlesinger, M J 1990.Heat shock proteins J Biol Chem 265:121112114 Schmitt, W and R.Haas 1994.Genetic analysis of the Helicobacter pylori vacuolating cytotoxin: structural similarities with IgA protease type of exported protein Mol Microbiol 12:307-319 Schneider C, S., E Nimmesgern ,0.OuerfeUi, S Danishefsky, N Rosen and F U Hartl 1996.Pharmacologic shifting of a balance between protein refolding a n d degradation mediated by Hsp9O Proc Natl Acad Sci USA 93:14536-14541 Schumacher, R j., W J Hansen, B.C Freeman, E Alnemri, G Litwack and D 0.Toft 1996 Cooperative action of Hsp70, Hsp90, and DnaJ proteins in protein renaturation Biochemistry 35:14889-14898 Scorpio, A,P Johnson, k Laquerre and D.Nelson 1994 Subcellular localization and chaperone activities of Borrelia burgdorferi Hsp6O and Hsp7O J Bacterial 176:6449-6456 Segal, E D., S Fallrow and L S Tompkins 1996.Helicobacter pylori attachment t o gastric cells induces cytoskeletal rearrangements and tyrosine phosphorylation of host cell proteins Proc Natl Acad Sci USA 93:1259-1264 Segal, E.D., C.Lange, A Covacci, L S Tompkins and S Falkow 1997 Induction of host signal transduction pathways by Helicobacter pylori Proc Natl Acad Sci USA 9475957599 Sharma S A,Tummuru M K R, Blaser M, J., Kerr L Dm Activation of IL-8 Gene Expression by Helicobacter pylori is regulated b y the transcription nuclear Factor-kB in Gastric Epithelial Cells 1998.J Immunol160: 2401-2407 Sherburne, Id and D.E.Taylor 1995.Helicobacterpylori expresses a complex surface carbohydrate, Lewis X Infect Immun 63:4564-4568 Sherman,P M 1993 Adherence and internalization of H pylori by epithelial cells in Helicobacter pylori: basic mechanisms to clinical cure Hunt R.H., Tytgat G N J, eds Hingham, MA USA:148-162 Simon, P.M., P.L Goode, k Mobasseri and Dm Zopf 1997 Inhibition of Helicobacter pylori binding to gastrointestinal epithelial cells by sialic acid-containing oligosaccharides Infect Immun 65:750-757 Sipoonen, P.,M Siurala and S Goodwin 1993.Histology and ultrastructure of Helicobacter pylori infections 37-62 in: Helicobacter pylori: Biology and Clinical Practice Skeen,lM.J:, M.k Miller, T M Shinnick and H R Ziegler 1996 Regulation of murine macrophage IL-12 production: activation of macrophages in vivo, restimulation in vitro, and modulation by other cytokines J Immunol 156:1196-1206 Slomiany,B L.,J.Bilski, J Sarosiek,V L N Murty, B Dworkin, K, VanHorn, J Zielenski and A Slomiany 1987 Campylobacterpyloridis degrades mucin and undermines gastric mucosal integrity Biochem Biophys Res Comm 144307-314 Slomiany, B L., J Sarosiek and A Slomiany 1987 Gastric mucus and the mucosal barrier Dig Dis Sci 5:125-145 Slomiany, B L., k Slomiany and G B.J Glass 1977.Glycolipids of the human gastric content Eur J Biochem 78:33-39 Schmiel, D H., S.T.Knight,J E Raulston, J Choong, C.H Davis, P B Wyrick 1991.Recombinant Escherichia coli clones expressing Chlamydia trachomatis gene products attach to human endometrial epithelial cells Infect Immun 59:4OOl-4012 Smith, k W.,B Chahal and D L French 1994.H pylori gene encoding an enzyme first classified as mucinase in Vibrio cholera Mol Microb 13:153-160 Smoot, D T., H L.T.Mobley, G R Chippendaele, J.F.Lewison and J H Resau 1991 Helicobacter pylori urease activity is toxic t o human gastric epithelial cells Infect Immun 59:1992-1994 Smoat, D T.,J H.Resau, T.Naab, B.C.Desbordes, Gilliam T.,BullHenry R, Curry S B., Nidiry J., Thorsby E.,Sewchand J., Mills-Robertson K 1993.Adhesion of Helicobacter pylori to cultured human gastric epithelial cells Infect Immun 61:350-355 SolLid, L M, D Kvale ,P.Brandtzaeg ,G Markussen and E Thorsby.1987 Interferon gamma enhances expression of secretory component, the epithelial receptor for polymeric immunoglobulins J Immunol138: 4303-4306 Spiegel, S and S Milstien 1995 Sphingolipid metabolites: members of a new class of lipid second messengers J Membrane Biol 146:225-237 Spiegelhalder, C., B Gerstenecker, k Kersten, E Schiltz, and M Kist 1993 Purification of Helicobacter pylori superoxide dismutase and cloning and sequencing of the gene Infect Immun 61: 5315-5325 Srnka, C A, M Tiemeyer, J H Gilbert, M Moreland, H Schweingruber, B W Delappe, P G James,T Gant, R E Willoughby, R H Yolken, M A Nashed, S k Abbas and R, A Laine 1992 Cell surface ligands for rotavirus - mouse Intestinal glycolipids and synthetic carbohydrate analogs Virology 190:794-805 Steer, H W and DmG Colin-Jones 1975 Mucosal changes in gastric ulceration and their response to carbenoxolone sodium Gut 16:590-597 Strijmberg, N.,M Ryd, k k Lindburg and K A Karlsson 1988 Studies on the binding of bacteria to glycolipids: two species of Propionibacterium apparently recognize separate epitopes on lactose of lactosylceramide FEBS Lett 232:193-198 Stromberg, N 1990 Carbohydrates as recognition molecules for bacterial adhesins: Methodology and characteristics Arch Oral Biol 35131s Stults, C L M., C H Sweeley and B A Macher 1989 Glycosphingolipids; structure biological source and properties Meth Enzymol 179:167-214 Suerbaum, S., C Josenhans and A Labigne 1993 Cloning and genetic characterization of the Helicobacter pylori and Helicobacter mustelae @aB flagellin genes and construction of H pylori flaA- and flaBnegative mutants b y electrophoration-mediated allelic exchange J Bacteriol.175: 3278-3288 Suerbaum, S., J.-M Thiberge, I Kansau,R L.Ferrem and A Labigne 1994 Helicobacter pylori hspA-hspB heat-shock gene cluster: nucleotide sequence, expression, putative function and immunogenicity Mol Microbial 14:959-974 Sugano, R,T.Tai, I Kawashima, M Kotani, H Natomi, S Kamisago, Y.Fukushima, Y.Yazaki and M Iwamori 1995 Localization of sulfatides in the epithelial lining of gastric mucosa: studies with a monoclond antibody t o sdfatides J Clin GastroenterolZl:S98-S103 Susumo, I 1981 Functional Gastric Morphology 517-549 In: J LR, in Physiology of the Gastrointestinal Tract Suzuki, Y., T.Nakao, T Ito, N.Watanabe, Y Toda, X Guiyun, T Suzuki, T Kobayashi, Y Kimura, A Yamada, K Sugawara, H Nishimura, F Kitame, K Nakmura, E Deya, M Kiso and k Hasegawa 1992 Structural determination of gangliosides that bind to influenza A, B, and C viruses by an improved binding assay: strain-specific receptor epitopes in sialo-sugar chains Virology lSS:l2l-l3l Svensson R2,R Lindstedt ,N.S Radin ,C Svanborg 1994 Epithelial glycosphingolipid expression a s determinant of bacterial adherence and cytokine production Infect Immun 62:4404-4410 Taglich, D., E Padan and S Schuldiner 1991 Overproduction and purification of a fbnctional Na+/H+ antiporter coded by nhaA (ant) from Escherichia coli J Biol Chem 266:11289-11294 Taguchi, H., Y.Makino and M Yoshida 1994 Monomeric chaperonin-60 and its 50 kDa fragment possess the ability t o interact with non-native proteins, to supress aggregations, and promote protein folding J Biol Chem 269: 8529-8534 Tamura, Y., P Peng,K Liu, M Daou and P.K Srivastava 1997 Immunotherapy of tumors with autologous tumor-derived heat shock protein preparations Science 278: 117-120 Tanphaichitr, N., J Smith, S Mongkolsirikieart, C Gradil and C A Lingwood 1993 Role of a gamete-specific sulfoglycolipid immobilizing protein on mouse sperm-egg binding Devel Biol 156:164-175 Tanphaichitr, M.,A Tayabali, C Gradil, S Juneja, M C LeveUe and C A Lingwood 1992 Role of germ cell specific sulfolipidimmobilizing protein (SLIP1) on mouse in vivo fertilization Mol Reprod Dev 32:17-22 Tarkkanen, J., T U.Kosunen and E.Saksela 1993 Contact of lymphocytes with Helicobacter pylori augments natural killer cell activity and induces production of gamma interferon Infect Immun 61:3Ol2-30 16 Tenebeg S , H, Miller-Podraza, & C Lampert, D J.Evans Jr., D G.Evans, D.Danielsson, K A Karlsson 1997 Carbohydrate binding specificity of the neutrophil-activating protein of Helicobacter pylori J Biol Chem 272:19067-19071 Tilly, K., H.Murialdo and C.Georgopolulos 1981 Identification of a second Escherichia coli groE gene whose product is necessary for bacteriophage morphogenesis Proc Natl Acad Sci USA 78: 1629-1633 Tilly, K, M N., M Zylicz and C Georgopolos 1983.The Dnak protein modulates the heat shock response of E coli Cell 34641-646 Tomb, J.-F., White,k R Kerlavage, R A Clayton,G G Sutton, R DmFleischmann, K A Ketch-, H P Klenk, S Gill, B A Dougherty, K Nelson, J Quackenbush, L Zhou, E F Hjrkness, S Peterson, B lo^, D Richardson, R Dodson, H G Khalak, A Glodek,K McKenney, L M Fitzegerald, N Lee, M D Adams, E.K Hickey,D E Berg, J D Gocayne, T.R Utterback, J.DmPeterson,J.M.Kelley, M D Cotton, J.M Weidman, C.Fujii, C.Bowman, L.Watthey, E.Wallin, W S Hayes, M Borodovsky, P D Karp, H Smith,C M Fraser and J C Venter 1997.The complete genome sequence of the gastric pathogen Helicobacter pylori Nature (London) 388:539-547 Tompkins, L.S and L S.Falkow 1995 The new path to preventing ulcers Science 267:1621-1622 Tortorella D., D Sesardic ,C S Dawes and E London 1995 Immunological analysis of the structure of diphteria toxin shows all three domains undergo structural changes at low pH J Biol Chem 270: 2743927445 Totten P A, C L Fennel and F C Tenover 1985 Campylobacter cinaedi and Campylobacter fennelliae: Two new ~ a r n ~ ~ l o b a c t & s ~ e c i e s associated with enteric disease in homosexual men J Infect Dis 151:131139 Tuomanen, E W., A 1985 Characterization of two adhesins of Bordetella pertussis for human ciliated respiratory epithelial cells J Infect Dis 152:118-125 Uchida, Y., K Matzuda, KOSasahara,H Kawabata and M Nishioka 1995 Irnmunohistochemistry of gap junctions in normal and diseased gastric rnucosa of humans Gastroenterology 109:1492-1496 Valkonen K and A.P Moran 1997.Identification of the Nacetylneuraminyllactose-specificlaminin-binding protein of Helicobacter pylori Infect Immun 65: 916-923 Valnes, K and P Brandtzaeg 1989 Subclass distribution of mucosal IgGproducing cells in gastritis Gut 30:322-326 Vanet k and A Labigne 1998 Evidence for specific secretion rather thari autolysis in the release of some Helicobacter pylori proteins Infect Immun 66:1023-1027 Verkleg, k J., R F Zwaal, B Roelofsen, P.Comfurius, D Kastelijn and L L van Deenen 1973 The asymmetric distribution of phospholipids in the human red cell membrane A combined study using phospholipases and freeze-etch electron microscopy Biochim Biophys Acta 323:178-193 Wang T-F., J-H Chang and C Wang 1993 Identification of the peptide binding domain of hsc7O J Biol Chem 268: 26049-26051 Warren, J and B Marshall 1983 Unidentified curved bacillus in the gastric epithelium in active chronic gastritis 1983 Lancet I:1273-1275 Watson, K 1990 Microbial stress proteins Adv Microb Phys 31:255258 Wadstrom, T., S Hirmo, H Novak ,k Guzman, M RignerPantzar, M Utt and A Aleljung.1997 Sulfatides inhibit binding of Helicobacter pylori to gastric cancer Kato 111 cell line Curr Microbiol 34267-272 Wiest, D., W.H Burgess,D.McKean ,K P Kearse and A Singer 1995 The molecular chaperone calnexin is expressed on the surface of immature thymocytes in association with clonotype-independent CD3 complexes EMBO J 14: 3425-3433 Wilkinson S M., J.R Uhl, B C KEne and F R Cockerill 3rd 1998 Assessment of invasion frequencies of cultured HEp-2 cells by clinical isolates of Helicobacter pylori using an acridine orange assay J Clin Path01 51:127-133 Williams, S E.and L A Turnberg 1980 Retardation of acid difusion by pig gastric mucus: A potential role in mucosal protection Gastroenterology 79:299-304 Winans, S C and P J Christie 1996 Adaptation of a conjugal transfer system for the export of pathogenic macromolecules Trends Microbiol4:64-68 Wosten M M., M Boeve, MeG Koot ,k C Nuene and B A Zeijst.1998 Identification of Campylobacter jejuni promoter sequences J Bacteriol180:594-599 Wyatt, J.I., B.J Rathbone, G M Soballa, T.Shalcrost, R V.Heatly, A T R Axon and M.F Dixon 1990 Gastric epithelium in the duodenun; its association with Helicobacter pylori and inflammation J Clin Path01 43981-986 Wyle F.A, A Tarnawski, D Schulman and W.Dabros 1990 Evidence for gastric mucosal cell invasion by C.pylori: an ultrastructural study J Clin Gastroenterol 12: S92-S98 W y m , R lkL, Jo R DAvie, R D COXand DmT Chuang 1994 Molecular chaperones: heat-shock proteins, foldases, and matchmakers J Lab Clin Med 124:31-36 Wahi, S., S Baghdiguian, H Moreau and J.Fantini 1992 Galactosyl ceramide(or a closely related molecule) is the receptor for human immunodeficiency virus type 1on human colon epithelial HT29 cells J Virol66:4848-4854 Yamaguchi, H., T.Osaki, N.Kurihar, H Taguchi, T.Hanawa,Y Yamamoto and S Kamiya 1997 Heat-shock protein 60 homologue of Helicobacter pylori is associated with adhesin of H.pylori to human gastric epithelial cells Med Microbiol46:825-83 Yamaguchi, H., T.Osaki, H Taguchi, j Hanawa,T Yamoto and S Kamiya 1996 Flow cytometric analysis of the heat shock protein 60 expressed o n the cell surace of Helicobacter pylori J M e d Microbiol 45:270277 Yamamori, T and T Yura 1980 Temperature-induced synthesis of specific proteins in Escherichia coli: evidence for transcriptional control J Bacterial 142:843-851 Yifrach and A Horovitz 1996 Allosteric control by ATP of nonfolded protein binding to GroEL J Biol255: 356-361 Yin, Y., F Zhang, V Ling and C H Arrowsmith 1995 Structural analysis and comparison of the C-terminal transport signal domains of hemolysin A and leukotoxin A FEBS Lett 366:1-5 Yiu, S C K and C k Ling~ood.1992 Polyisobutylmethacrylate modifies glycolipid binding specificity of verotoxin in thin layer chromatogram overlay procedures Anal Biochem 202:188-192 Yokota, K., Y Hira, M Haque, S Hayashi, H Isogai, T Sugiyama, E Nagamachi, Y T d a d a , N.Fyjii and K Oguma 1994 Heat shock protein produced by Helicobacter pylori Microbiol Imrnunol38:403-405 Yura, T.,H o Nagai and H Mori 1993 Regulation of the heat-shock response in bacteria Annu Rev Microb 47:321-350 Zabn R,A M Buckle,S Perrett, C M Johnson,F.J Corrales,R Goibick, A R Fersht.1996 Chaperone activity and structure of monomeric polypeptide binding domains of GroEL Proc Natl Acad Sci USA 93: 1502415029 Zeistra-Ryalls,J.,0.Fayet and C.Georgopodos 1991.The universally conserved GroE (hsp 60) chaperonins Annu Rev Microbiol 45:301-325 Zhaohui, X,A L Hoewich and P B.Sigler 1997 The crystal structure of the asymmetric GroEL-GroES-(ADP)7 chaperonine complex Nature (London) 388: 741-750 Zhu, X., X Xhao ,W.F Burkholder, k Gragerov, C Ogata M., M E Gottesman and W.A Hendrickson 1996 Structural analysis of substrate binding by the molecular chaperone DnaK Science 272: 1606-1614 Zilberstein, D.1994.The role of pH and temperature in the development of Leishmania parasites Annu Rev Microbiol 48:449-470