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研究生:林稚容
研究生(外文):Tzu-Lung Lin
論文名稱:以跳躍因子系統性突變發現幽門桿菌一個全新的限制-修飾系統
論文名稱(外文):Isolation of a Novel Restriction-Modification System in Helicobacter pylori by Transposon Mutagenesis
指導教授:王錦堂王錦堂引用關係
指導教授(外文):Jin-Town Wang
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:微生物學研究所
學門:生命科學學門
學類:微生物學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:中文
論文頁數:74
中文關鍵詞:限制-修飾系統跳躍因子幽門桿菌黏著因子
外文關鍵詞:restriction-modification systemHelicobacter pyloriadhesintransposon
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利用1500株幽門桿菌突變株,篩選其對胃癌上皮細胞株黏著能力,以尋找幽門桿菌之黏著因子,發現6株突變株黏著能力降低,但光學及電子顯微鏡下觀察發現菌體型態明顯延長。定序後發現這6株突變株破壞的基因是相同的,但幽門桿菌26695及J99菌株全基因體中並無該核酸及胺基酸的相似序列。這個開放讀架由1617個鹼基對組成,胺基酸序列和Bacillus halodurans的一個推斷的單股剪切酶有24%的相似性,和二個第IIS型限制內切酶,PleI和MlyI,分別有23%及20%相似度。分析這個純化的未知限制酶,HpyC1I,其辨識及剪切位置為5’-CCATC(4/5)-3’。此基因上游二個開放讀架,M1.HpyC1I和M2.HpyC1I,都含有甲基轉移酶的弁鈰礡A因此這三個基因可能構成一個調控組,且負責限制-修飾弁遄C這段序列和全基因體比較,G+C含量明顯較低,推測可能經由水平基因轉移獲得。測試15株幽門桿菌菌株,有9株菌株具有這個HpyC1I限制-修飾基因。質體DNA轉型和染色體裁切的實驗證明擁有HpyC1I限制-修飾系統可以使DNA受到保護不被HpyC1I剪切。在本研究中我們發現一個新的限制-修飾系統-HpyC1I限制-修飾系統,此系統存在於~60%的幽門桿菌菌株中,且破壞會導致細菌型態延長和HpyC1I限制酶的裁切。
To identify adhesion-associated loci, we constructed a mutant library from a clinical isolate of Helicobacter pylori. A total of 1500 mutant strains were screened by cell adhesion assay. We identified six mutants from NTUH-C1 strain that exhibited decreased adherence and cell elongation. Inverse polymerase chain reaction and DNA sequencing revealed that the same locus was interrupted in these six mutants. Nucleotide and amino acid sequences showed no homologies with H. pylori 26695 and J99 strains. This novel open reading frame (ORF) contained 1617 base pairs. The amino acid sequence shared 24% identity with a putative nicking enzyme in Bacillus halodurans, and 23% and 20% identity with Type-IIS restriction endonucleases PleI and MlyI, respectively. The purified protein, HpyC1I, showed endonuclease activity with the recognition and cleavage site 5’-CCATC(4/5)-3’. Two ORFs were located upstream of the gene encoding HpyC1I. Together, HpyC1I and these two putative methyltransferases (M1.HpyC1I and M2.HpyC1I) function as a restriction-modification (R-M) system. The HpyC1I R-M genes were found in nine of the fifteen H. pylori strains tested. When compared to the full genome, significantly lower G+C content of HpyC1I R-M genes implied that these genes might have been acquired by horizontal gene transfer. Plasmid DNA transformation efficiencies and chromosomal DNA digestion assays demonstrated protection from HpyC1I digestion by the R-M system. In conclusion, we have identified a novel R-M system present in ~60% of H. pylori strains. Disruption of this R-M system results in cell elongation and susceptibility to HpyC1I digestion.
誌謝………………………………………………………………………………….. I
中文摘要…………………………………………………………………………….. II
英文摘要…………………………………………………………………………….. III
第一章 緒論
(一) 幽門桿菌的感染、傳染途徑及治療………………………………………… 1
(二) 幽門桿菌的基因體…………………………………………………………… 2
(三) 幽門桿菌的致病因子………………………………………………………… 2
第二章 研究目的……………………………………………………………………. 9
第三章 實驗材料及方法
(1) 質體及菌株…………………………………………………………………..... 10
(2) 培養基………………………………………………………………………….. 12
(3) 引子…………………………………………………………………………….. 13
(4) 研究方法
(一) 幽門桿菌突變株基因庫的建構及代表性、重複性之計算
1.1 幽門桿菌染色體DNA的萃取……………………………………………... 14
1.2 染色體DNA之部分剪切及片段回收……………………………………... 15
1.3 幽門桿菌基因庫……………………………………………………………. 15
1.4 在大腸桿菌中對幽門桿菌基因庫進行轉位作用…………………………. 16
1.5 一次96個轉位作用後的大腸桿菌自然轉型到幽門桿菌………………... 17
1.6 幽門桿菌突變株基因庫的代表性和重複性分析…………………………. 17
(二) 突變株之細胞黏著能力篩選……………………………………………..... 17
(三) 細菌基本型態觀察………………………………………………………..... 18
(四) 尋找及分析被破壞的基因………………………………………………..... 19
(五) 基因重新破壞及補回
5.1 重新破壞hpyC1IR基因…………………………………………………… 20
5.2 補回hpyC1IR………………………………………………………………. 21
5.3 hpyC1IM1突變株的建構………………………………………………..... 21
5.4 hpyC1IM2突變株的建構………………………………………………..... 22
(六) 突變株的轉型效率分析…………………………………………………..... 22
(七) 表現及純化HpyC1I蛋白質
7.1 hpyC1IR基因表現載體的剪接……………………………………………. 24
7.2 His標誌HpyC1I蛋白質表現…………………………………………...… 25
7.3 大量純化His標誌HpyC1I蛋白質……………………………………….. 26
(八) HpyC1I辨識及剪切序列…………………………………………………… 26
(九) 幽門桿菌DNA的剪切……………………………………………………… 27
(十) 幽門桿菌菌株HpyC1I 限制-修飾系統的差異…………………………..... 28
(十一) hpyC1IR突變株RNA表現分析
11.1 RNA抽取………………………………………………………………..... 28
11.2 biotin-cDNA探針的合成…………………………………………………. 29
11.3 雜交及呈色………………………………………………………………... 29
11.4 結果分析比較……………………………………………………………... 30
第四章 結果
(一) 幽門桿菌突變株基因庫的建構及代表性、重複性之計算………………… 31
(二) 突變株之細胞黏著能力篩選………………………………………………… 31
(三) 細菌基本型態觀察…………………………………………………………… 31
(四) 尋找及分析被破壞的基因…………………………………………………… 32
(五) 基因重新破壞及補回………………………………………………………… 33
(六) 突變株的轉型效率分析……………………………………………………… 34
(七) 表現及純化HpyC1I蛋白質…………………………………………………. 35
(八) HpyC1I辨識及剪切序列…………………………………………………..... 37
(九) 幽門桿菌DNA的剪切……………………………………………………..... 38
(十) 幽門桿菌菌株HpyC1I 限制-修飾系統的差異…………………………...... 39
(十一) hpyC1IR突變株RNA表現分析…………………………………………. 40
第五章 討論..................................................................................................... 41
第六章 附圖表
圖一:以跳躍因子穿梭突變法建構幽門桿菌突變株基因庫。………………..... 47
圖二:MiniTn3-Km跳躍因子基因結構圖。……………………………………... 48
圖三:反向聚合酶連鎖反應及定序使用之引子位置圖。……………………..... 49
圖四:重新破壞hpyC1IR基因的質體圖和獲得突變株之染色體結構。……… 50
圖五:補回hpyC1IR的質體圖和補回hpyC1IR菌株的染色體結構。…………………………………………………………………………………. 51
圖六:hpyC1IR基因表現載體的剪接圖。………………………………………. 52
圖七: 幽門桿菌NTUH-C1原生株及6株黏著下降的突變株的黏著分析。………………………………………………………………………………..... 53
圖八: 幽門桿菌原生株、突變株六、重新破壞hpyC1IR突變株和補回hpyC1IR菌株光學顯微鏡下觀察之細菌型態。…………………………………. 54
圖九: 幽門桿菌NTUH-C1原生株HpyC1I限制-修飾基因的排列和26695及J99菌株相對的區域。…………………………………………………………….. 55
圖十: 幽門桿菌NTUH-C1原生株、突變株六、hpyC1IR突變株及hpyC1IR補回菌株的黏著分析。…………………………………………………………..... 56
圖十一: HpyC1I蛋白質表現及純化和酵素弁鄐尷R。……………………...... 57
圖十二: HpyC1I和BccI裁切DNA的結果。……………………………………. 58
圖十三: 幽門桿菌DNA以HpyC1I剪切。……………………………………... 59
圖十四: 幽門桿菌菌株間HpyC1I限制-修飾系統的分布。……………………... 60
表一: 幽門桿菌hpyC1IM1, hpyC1IM2 和hpyC1IR突變株DNA轉型效率。... 61
表二: 藉由轉殖及定序HpyC1I裁切lamda DNA片段以分析HpyC1I辨識及剪切序列和位置 (T4 DNA聚合酶)。…………………………………………….. 62
表三: 藉由轉殖及定序HpyC1I裁切lamda DNA片段以分析HpyC1I辨識及剪切序列和位置 (Klenow聚合酶)。…………………………………………….. 63
表四: 幽門桿菌原生株和hpyC1IR突變株RNA表現量差異比較。…………… 64
第七章 參考文獻……………………………………………………………………. 65
1.Akopyants NS, Fradkov A, Diatchenko L, Hill JE, Siebert PD, Lukyanov SA, Sverdlov ED, Berg DE. PCR-based subtractive hybridization and differences in gene content among strains of Helicobacter pylori. Proc Natl Acad Sci U S A. 1998;95(22):13108-13.

2.Alm RA, Ling LS, Moir DT, King BL, Brown ED, Doig PC, Smith DR, Noonan B, Guild BC, deJonge BL, Carmel G, Tummino PJ, Caruso A, Uria-Nickelsen M, Mills DM, Ives C, Gibson R, Merberg D, Mills SD, Jiang Q, Taylor DE, Vovis GF, Trust TJ. Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori. Nature. 1999;397(6715):176-80.

3.Ando T, Xu Q, Torres M, Kusugami K, Israel DA, Blaser MJ. Restriction-modification system differences in Helicobacter pylori are a barrier to interstrain plasmid transfer. Mol Microbiol. 2000;37(5):1052-65.

4.Ang S, Lee CZ, Peck K, Sindici M, Matrubutham U, Gleeson MA, Wang JT. Acid-induced gene expression in Helicobacter pylori: study in genomic scale by microarray. Infect Immun. 2001;69(3):1679-86.

5.Aras RA, Small AJ, Ando T, Blaser MJ. Helicobacter pylori interstrain restriction-modification diversity prevents genome subversion by chromosomal DNA from competing strains. Nucleic Acids Res. 2002;30(24):5391-7.

6.Asahi M, Azuma T, Ito S, Ito Y, Suto H, Nagai Y, Tsubokawa M, Tohyama Y, Maeda S, Omata M, Suzuki T, Sasakawa C. Helicobacter pylori CagA protein can be tyrosine phosphorylated in gastric epithelial cells. J Exp Med. 2000;191(4):593-602.

7.Bachmann, B. J. Derivations and genotypes of some mutant derivatives of Escherichia coli, in E. coli and Salmonella typhimurium. Cellular and Molecular biology, 2nd ed. (Neidhardt, F. C., Curtiss, III, R., Ingraham, J. L., Lin, E. C. C., Low, K. B., Magasanik, B., ReGnikoff, W. S., Riely, M., Schaechter, M., and Umbarger, H. E., eds.), 1996; ASM, pp. 2460-2488.

8.Blaser MJ. Hypotheses on the pathogenesis and natural history of Helicobacter pylori-induced inflammation. Gastroenterology. 1992;102(2):720-7.

9.Boren T, Falk P, Roth KA, Larson G, Normark S. Attachment of Helicobacter pylori to human gastric epithelium mediated by blood group antigens. Science. 1993;262(5141):1892-5.

10.Boyer, H. W. and Roulland-D, D. A complementation analysis of the restriction and modification of DNA in Escherichia coli. J. Mol. Biol. 1969; 41: 459-472.

11.Censini S, Lange C, Xiang Z, Crabtree JE, Ghiara P, Borodovsky M, Rappuoli R, Covacci A. cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors. Proc Natl Acad Sci U S A. 1996;93(25):14648-53.

12.Chang KC, Yeh YC, Lin TL, Wang JT. Identification of genes associated with natural competence in Helicobacter pylori by transposon shuttle random mutagenesis. Biochem Biophys Res Commun. 2001;288(4):961-8.

13.Chen JJ, Wu R, Yang PC, Huang JY, Sher YP, Han MH, Kao WC, Lee PJ, Chiu TF, Chang F, Chu YW, Wu CW, Peck K. Profiling expression patterns and isolating differentially expressed genes by cDNA microarray system with colorimetry detection. Genomics. 1998;51(3):313-24.

14.Clyne M, Drumm B. The urease enzyme of Helicobacter pylori does not function as an adhesin. Infect Immun. 1996;64(7):2817-20.

15.Covacci A, Censini S, Bugnoli M, Petracca R, Burroni D, Macchia G, Massone A, Papini E, Xiang Z, Figura N. Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer. Proc Natl Acad Sci U S A. 1993;90(12):5791-5.

16.Donahue JP, Israel DA, Torres VJ, Necheva AS, Miller GG. Inactivation of a Helicobacter pylori DNA methyltransferase alters dnaK operon expression following host-cell adherence. FEMS Microbiol Lett. 2002;208(2):295-301.

17.Dunn, B. E., G. P. Campbell, G. I. Perez-Perez, M. J. Blaser. Purification and characterization of urease from Helicobacter pylori. J Biol Chem. 1900; 265:9464-9469.

18.Eaton, K. A., C. L. Brooks, D. R. Morgan, S. Krakowka. Essential role of urease in pathogenesis of gastritis induced by Helicobacter pylori in gnotobiotic piglets. Infect Immun. 1991; 59:2470-5.

19.Eaton, K. A., S. Suerbaum, C. Josenhans, S. Krakowka. Colonization of gnotobiotic piglets by Helicobacter pylori deficient in two flagellin genes. Infect Immun. 1996; 64:2445-8.

20.Evans DG, Karjalainen TK, Evans DJ Jr, Graham DY, Lee CH. Cloning, nucleotide sequence, and expression of a gene encoding an adhesin subunit protein of Helicobacter pylori. J Bacteriol. 1993;175(3):674-83.

21.Evans DJ Jr, Evans DG, Takemura T, Nakano H, Lampert HC, Graham DY, Granger DN, Kvietys PR. Characterization of a Helicobacter pylori neutrophil-activating protein. Infect Immun. 1995;63(6):2213-20.

22.Falk P, Roth KA, Boren T, Westblom TU, Gordon JI, Normark S. An in vitro adherence assay reveals that Helicobacter pylori exhibits cell lineage-specific tropism in the human gastric epithelium. Proc Natl Acad Sci U S A. 1993;90(5):2035-9.

23.Fan XG, Chua A, Fan XJ, Keeling PW. Increased gastric production of interleukin-8 and tumour necrosis factor in patients with Helicobacter pylori infection. J Clin Pathol. 1995;48(2):133-6.

24.Gordon D. CagA protein from Helicobacter pylori is a Trojan Horse to epithelial cells. Gastroenterology. 2000;118(5):817.

25.Hallstone AE, Perez EA. Blood type and the risk of gastric disease. Science. 1994;264(5164):1386-8.

26.Heuermann D, Haas R. A stable shuttle vector system for efficient genetic complementation of Helicobacter pylori strains by transformation and conjugation. Mol Gen Genet. 1998;257(5):519-28.

27.Higashi H, Tsutsumi R, Muto S, Sugiyama T, Azuma T, Asaka M, Hatakeyama M. SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. Science. 2002;295(5555):683-6.

28.Hsieh PF, Yang JC, Lin JT, Wang JT. Molecular mechanisms of clarithromycin resistance in Helicobacter pylori. J Formos Med Assoc. 1998;97(7):445-52.

29.Huang J, O''Toole PW, Doig P, Trust TJ. Stimulation of interleukin-8 production in epithelial cell lines by Helicobacter pylori. Infect Immun. 1995;63(5):1732-8.

30.Huesca M, Goodwin A, Bhagwansingh A, Hoffman P, Lingwood CA. Characterization of an acidic-pH-inducible stress protein (hsp70), a putative sulfatide binding adhesin, from Helicobacter pylori. Infect Immun. 1998;66(9):4061-7.

31.Ilver D, Arnqvist A, Ogren J, Frick IM, Kersulyte D, Incecik ET, Berg DE, Covacci A, Engstrand L, Boren T. Helicobacter pylori adhesin binding fucosylated histo-blood group antigens revealed by retagging. Science. 1998;279(5349):373-7.

32.Jiang SY, Shyu RY, Chen HY, Lee MM, Wu KL, Yeh MY. In vitro and in vivo growth inhibition of SC-M1 gastric cancer cells by retinoic acid. Oncology. 1996;53(4):334-40.

33.Jones AC, Logan RP, Foynes S, Cockayne A, Wren BW, Penn CW. A flagellar sheath protein of Helicobacter pylori is identical to HpaA, a putative N-acetylneuraminyllactose-binding hemagglutinin, but is not an adhesin for AGS cells. J Bacteriol. 1997;179(17):5643-7.

34.Kovall RA, Matthews BW. Type II restriction endonucleases: structural, functional and evolutionary relationships. Curr Opin Chem Biol. 1999;3(5):578-83.

35.Labigne, A. Random mutagenesis of H. pylori genome, 1997; p. 153-163. Clayton, C. L. and Mobley, H. L. T. (ed.) Helicobacter pylori protocols. Humana Press Inc. Toyowa, New Jersey.

36.Labigne-Roussel, A., Courcoux, P., and Tompkins, L. Cloning of Campylobacter jejuni genes required for leucine biosynthesis, and construction of leu-negative mutant of C. jejuni by shuttle mutagenesis. Res. Microbiol. 1992; 143: 15-26.

37.Lin JT, Wang JT, Wang TH, Wu MS, Lee TK, Chen CJ. Helicobacter pylori infection in a randomly selected population, healthy volunteers, and patients with gastric ulcer and gastric adenocarcinoma. A seroprevalence study in Taiwan. Scand J Gastroenterol. 1993;28(12):1067-72.

38.Lin LF, Posfai J, Roberts RJ, Kong H. Comparative genomics of the restriction-modification systems in Helicobacter pylori. Proc Natl Acad Sci U S A. 2001;98(5):2740-5.

39.Maeda S, Yoshida H, Ogura K, Mitsuno Y, Hirata Y, Yamaji Y, Akanuma M, Shiratori Y, Omata M. H. pylori activates NF-kappaB through a signaling pathway involving IkappaB kinases, NF-kappaB-inducing kinase, TRAF2, and TRAF6 in gastric cancer cells. Gastroenterology. 2000; 119(1): 97-108.

40.Mahdavi J, Sonden B, Hurtig M, Olfat FO, Forsberg L, Roche N, Angstrom J, Larsson T, Teneberg S, Karlsson KA, Altraja S, Wadstrom T, Kersulyte D, Berg DE, Dubois A, Petersson C, Magnusson KE, Norberg T, Lindh F, Lundskog BB, Arnqvist A, Hammarstrom L, Boren T. Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation. Science. 2002;297(5581):573-8.

41.Marshall BJ, Barrett LJ, Prakash C, McCallum RW, Guerrant RL. Urea protects Helicobacter (Campylobacter) pylori from the bactericidal effect of acid. Gastroenterology. 1990;99(3):697-702.

42.Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet. 1984;1(8390):1311-5.

43.Moran AP. The role of lipopolysaccharide in Helicobacter pylori pathogenesis. Aliment Pharmacol Ther. 1996;10 Suppl 1:39-50.

44.Nomura A, Stemmermann GN, Chyou PH, Kato I, Perez-Perez GI, Blaser MJ. Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. N Engl J Med. 1991;325(16):1132-6.

45.Odenbreit S, Puls J, Sedlmaier B, Gerland E, Fischer W, Haas R. Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion. Science. 2000;287(5457):1497-500.

46.Odenbreit S, Till M, Haas R. Optimized BlaM-transposon shuttle mutagenesis of Helicobacter pylori allows the identification of novel genetic loci involved in bacterial virulence. Mol Microbiol. 1996;20(2):361-73.

47.Odenbreit S, Till M, Hofreuter D, Faller G, Haas R. Genetic and functional characterization of the alpAB gene locus essential for the adhesion of Helicobacter pylori to human gastric tissue. Mol Microbiol. 1999;31(5):1537-48.

48.Parsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH, Orentreich N, Sibley RK. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med. 1991;325(16):1127-31.

49.Peck B, Ortkamp M, Diehl KD, Hundt E, Knapp B. Conservation, localization and expression of HopZ, a protein involved in adhesion of Helicobacter pylori. Nucleic Acids Res. 1999;27(16):3325-33.

50.Peek RM Jr, Thompson SA, Donahue JP, Tham KT, Atherton JC, Blaser MJ, Miller GG. Adherence to gastric epithelial cells induces expression of a Helicobacter pylori gene, iceA, that is associated with clinical outcome. Proc Assoc Am Physicians. 1998;110(6):531-44.

51.Roberts RJ, Belfort M, Bestor T, Bhagwat AS, Bickle TA, Bitinaite J, Blumenthal RM, Degtyarev SKh, Dryden DT, Dybvig K, Firman K, Gromova ES, Gumport RI, Halford SE, Hattman S, Heitman J, Hornby DP, Janulaitis A, Jeltsch A, Josephsen J, Kiss A, Klaenhammer TR, Kobayashi I, Kong H, Kruger DH, Lacks S, Marinus MG, Miyahara M, Morgan RD, Murray NE, Nagaraja V, Piekarowicz A, Pingoud A, Raleigh E, Rao DN, Reich N, Repin VE, Selker EU, Shaw PC, Stein DC, Stoddard BL, Szybalski W, Trautner TA, Van Etten JL, Vitor JM, Wilson GG, Xu SY. A nomenclature for restriction enzymes, DNA methyltransferases, homing endonucleases and their genes. Nucleic Acids Res. 2003;31(7):1805-12.

52.Roberts RJ, Vincze T, Posfai J, Macelis D. REBASE: restriction enzymes and methyltransferases. Nucleic Acids Res. 2003;31(1):418-20.

53.Saitoh T, Natomi H, Zhao WL, Okuzumi K, Sugano K, Iwamori M, Nagai Y. Identification of glycolipid receptors for Helicobacter pylori by TLC-immunostaining. FEBS Lett. 1991;282(2):385-7.

54.Satin, B., G. Del Giudice, V. Della Bianca, S. Dusi, C. Laudanna, F. Tonello, D. Kelleher, R. Rappuoli, C. Montecucco, F. Rossi. The neutrophil-activating protein (HP-NAP) of Helicobacter pylori is a protective antigen and a major virulence factor. J Exp Med. 2000; 191:1467-1476.

55.Schmitt W, Haas R. Genetic analysis of the Helicobacter pylori vacuolating cytotoxin: structural similarities with the IgA protease type of exported protein. Mol Microbiol. 1994;12(2):307-19.

56.Segal ED, Lange C, Covacci A, Tompkins LS, Falkow S. Induction of host signal transduction pathways by Helicobacter pylori. Proc Natl Acad Sci U S A. 1997;94(14):7595-9.

57.Seifert, H. S., So, M., and Heffron, F. Shuttle mutagenesis: a method of transposon mutagenesis for Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 1985; 83: 735-739.

58.Selbach M, Moese S, Hauck CR, Meyer TF, Backert S. Src is the kinase of the Helicobacter pylori CagA protein in vitro and in vivo. J Biol Chem. 2002;277(9):6775-8.

59.Skowron PM, Majewski J, Zylicz-Stachula A, Rutkowska SM, Jaworowska I, Harasimowicz-Slowinska RI. A new Thermus sp. class-IIS enzyme sub-family: isolation of a ''twin'' endonuclease TspDTI with a novel specificity 5''-ATGAA(N(11/9))-3'', related to TspGWI, TaqII and Tth111II. Nucleic Acids Res. 2003;31(14):e74.

60.Stein M, Rappuoli R, Covacci A. Tyrosine phosphorylation of the Helicobacter pylori CagA antigen after cag-driven host cell translocation. Proc Natl Acad Sci U S A. 2000;97(3):1263-8.

61.Su B, Johansson S, Fallman M, Patarroyo M, Granstrom M, Normark S. Signal transduction-mediated adherence and entry of Helicobacter pylori into cultured cells. Gastroenterology. 1999;117(3):595-604.

62.Taylor, D. E., Ge, Z., Purych, D., Lo, T., and Hiratsuka, K. Cloning and sequence analysis of two copies of a 23S rRNA gene from Helicobacter pylori and association of clarithromycin resistance with 23S rRNA mutations. Antimicrob Agents Chemother 1997; 41 (12): 2621-2628.

63.Tomb JF, White O, Kerlavage AR, Clayton RA, Sutton GG, Fleischmann RD, Ketchum KA, Klenk HP, Gill S, Dougherty BA, Nelson K, Quackenbush J, Zhou L, Kirkness EF, Peterson S, Loftus B, Richardson D, Dodson R, Khalak HG, Glodek A, McKenney K, Fitzegerald LM, Lee N, Adams MD, Venter JC. The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature. 1997;388(6642):539-47.

64.Tummuru MK, Cover TL, Blaser MJ. Cloning and expression of a high-molecular-mass major antigen of Helicobacter pylori: evidence of linkage to cytotoxin production. Infect Immun. 1993;61(5):1799-809.

65.Tzouvelekis LS, Mentis AF, Makris AM, Spiliadis C, Blackwell C, Weir DM. In vitro binding of Helicobacter pylori to human gastric mucin. Infect Immun. 1991;59(11):4252-4.
66.Umlauft F, Keeffe EB, Offner F, Weiss G, Feichtinger H, Lehmann E, Kilga-Nogler S, Schwab G, Propst A, Grussnewald K, Judmaier G. Helicobacter pylori infection and blood group antigens: lack of clinical association. Am J Gastroenterol. 1996;91(10):2135-8.

67.Versalovic, J., Shortridge, D., Kibler, K., Griffy, M. V., Beyer, J., Flamm, R. K., Tanaka, S. K., Graham, D. Y., and Go, M. F. Mutations in 23S rRNA are associated with clarithromycin resistance in Helicobacter pylori. Antimicrob Agents Chemother 1996; 40: 477-480.

68.Wang G, Humayun MZ, Taylor DE. Mutation as an origin of genetic variability in Helicobacter pylori. Trends Microbiol. 1999;7(12):488-93.

69.Wang Y, Roos KP, Taylor DE. Transformation of Helicobacter pylori by chromosomal metronidazole resistance and by a plasmid with a selectable chloramphenicol resistance marker. J Gen Microbiol. 1993;139 ( Pt 10):2485-93.

70.Wilson GG, Murray NE. Restriction and modification systems. Annu Rev Genet. 1991;25:585-627.

71.Wotherspoon AC, Doglioni C, Diss TC, Pan L, Moschini A, de Boni M, Isaacson PG. Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori. Lancet. 1993;342(8871):575-7.

72.Xu Q, Peek RM Jr, Miller GG, Blaser MJ. The Helicobacter pylori genome is modified at CATG by the product of hpyIM. J Bacteriol. 1997;179(21):6807-15.
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