Abstract
his review summarizes the most recent data on the biological characteristics of Helicobacter pylori (morphological, cultural, biochemical). H. pylori pathogenicity factors promoting colonization, adhesion, biofilm formation, aggression, and cytotoxicity, their contribution to the pathogenesis of diseases as well as the possible relationships with various clinical outcomes are described in detail. The genetic heterogeneity of H. pylori strains which can determine different clinical manifestations and have significance for conducting epidemiological studies is also considered.
Kazan Research Institute of Epidemiology and Microbiology, Kazan, Russia
Kazan State Medical University, Kazan, Russia
Kazan Research Institute of Epidemiology and Microbiology, Kazan, Russia
Kazan State Medical University, Kazan, Russia
-
1.
Marshall B.J., Warren L.R. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet. 1984;1(8390):1311-1315.
-
2.
Goodwin C.S., Armstrong J.A., Chilvers T., et al. Transfer of Campylobacter pylori and Campylobacter mustelae to Helicobacter gen. nov. as Helicobacter pylori comb. nov. and Helicobacter mustelae comb. nov., respectively. Int J Syst Bacteriol. 1989;39:397-405.
-
3.
Radin J.N., Gaddy J.A., Gonzalez-Rivera C., et al. Flagellar localization of a Helicobacter pylori autotransporter protein. MBio. 2013;4(2):e00613-12.
-
4.
Qin Z., Lin W.T., Zhu S., Franco A.T., Liu J. Imaging the motility and chemotaxis machineries in Helicobacter pylori by cryo-electron tomography. J Bacteriol. 2016;pii:JB.00695-16.
-
5.
Willen R., Carlen B., Wang X., et al. Morphologic conversion of Helicobacter pylori from spiral to coccoid form. Scanning (SEM) and transmission electron microscopy (TEM) suggest viability. Ups J Med Sci. 2000;105(1):31-40.
-
6.
Saito N., Konishi K., Sato F., et al. Plural transformation-processes from spiral to coccoid Helicobacter pylori and its viability. J Infect. 2003;46:49-55.
-
7.
Can F., Karahan C., Dolapci I., et al. Urease activity and urea gene sequencing of coccoid forms of H. pylori induced by different factors. Curr Microbiol. 2008;56:150-155.
-
8.
Xia H.X., Keane C.T., O’Morain C.A. Culture of Helicobacter pylori under aerobic conditions on solid media. Eur J Clin Microbiol Infect Dis. 1994;13:406-409.
-
9.
Bury-Mone S., Kaakoush N.O., Asencio C., et al. Is Helicobacter pylori a true microaerophile? Helicobacter. 2006;11:296-303.
-
10.
Mégraud F., Bonnet F., Garnier M., Lamouliatte H. Characterization of Campylobacter pyloridis by culture, enzymatic profile, and protein content. J Clin Microbiol. 1985;22:1007-1010.
-
11.
Westblom T.U., Madan E., Midkiff B.R. Egg yolk emulsion agar, a new medium for the cultivation of Helicobacter pylori. J Clin Microbiol. 1991;29:819-821.
-
12.
Hazell S.L., Markesich D.C., Evans D.J., Evans D.G., Graham D.Y. Influence of media supplements on growth and survival of Campylobacter pylori. Eur J Clin Microbiol Infect Dis. 1989;8:597-602.
-
13.
Buck G.E., Smith J.S. Medium supplementation for growth of Campylobacter pyloridis. J Clin Microbiol. 1987;25:597-599.
-
14.
Olivieri R., Bugnoli M., Armellini D. Growth of Helicobacter pylori in media containing cyclodextrins. J Clin Microbiol. 1993;31:160-162.
-
15.
Cellini L., Allocati N., Piccolomini R., et al. New plate medium for growth and detection of urease activity of Helicobacter pylori. J Clin Microbiol. 1992;30:1351-1353.
-
16.
Queiroz D.M., Mendes E.N., Rocha G.A. Indicator medium for isolation of Campylobacter pylori. J Clin Microbiol. 1987;25:23782379.
-
17.
Jiang X.P., Doyle M.P. Growth supplements for Helicobacter pylori. J Clin Microbiol. 2000;38:1984-1987.
-
18.
Degnan A.J., Sonzogni W.C., Standridge J.H. Development of a Plating Medium for Selection of Helicobacter pylori from Water Samples. Applied Environment Microbiol. 2003;69(5):2914-2918.
-
19.
Isaeva G., Pozdeev O.K. Domestic chromogenic medium for isolation of Helicobacter pylori. Klin Lab Diagn. 2009;8:35-37.
-
20.
Murano A., Miyake M., Kato J., et al. Enhancement of the growth of Helicobacter pylori in Brucella broth by hydrogen peroxide. Microbiol Immunol. 1999;43(11):1009-1015.
-
21.
Morshed M.G., Karita M., Konishi H., Okita K., Nakazawa T. Growth medium containing cyclodextrin and low concentration of horse serum for cultivation of Helicobacter pylori. Microbiol Immunol. 1994;38(11):897-900.
-
22.
Tee W., Fairley S., Smallwood R., et al. Comparative evaluation of three selective media and a nonselective medium for the culture of Helicobacter pylori from gastric biopsies. J Clin Microbiol. 1991;29:2587-2589.
-
23.
Westblom T.U., Phadnis S., Langenberg W., et al. Catalase negative mutants of Helicobacter pylori. Eur J Clin Microbiol Infect Dis. 1992;11:522-526.
-
24.
Eaton K.A., Morgan D.R., Krakowka S. Motility as a factor in the colonisation of gnotobiotic piglets by Helicobacter pylori. J Med Microbiol. 1992;37(2):123-127.
-
25.
Tang R.X., Luo D.J., Sun A.H., Yan J. Diversity of Helicobacter pylori isolates in expression of antigens and induction of antibodies. World J Gastroenterol. 2008;14(30):4816-4822.
-
26.
Lowenthal A.C., Hill M., Sycuro L.K., et al. Functional analysis of the Helicobacter pylori flagellar switch proteins. J Bacteriol. 2009;191(23):7147-7156.
-
27.
McGee D.J., Langford M.L., Watson E.L., et al. Colonization and inflammation deficiencies in Mongolian gerbils infected by Helicobacter pylori chemotaxis mutants. Infect Immun. 2005;73(3):1820-1827.
-
28.
Lee A.Y., Kao C.Y., Wang Y.K., et al. Inactivation of ferric uptake regulator (Fur) attenuates Helicobacter pylori J99 motility by disturbing the flagellar motor switch and autoindicer-2 production. Helicobacter. 2017;22(4):e12388.
-
29.
Zhong Y., Andert F., Kruse T., et al. Helicobacter pylori HP0231 influences bacterial virulence and essential for gastric colonization. PLoS One. 2016;11:e0154643.
-
30.
Cole S.P., Harwood J., Lee R., et al. Characterization of monospecies biofilm formation by Helicobacter pylori. J Bacteriol. 2003;186(10):3124-3132.
-
31.
Coticchia J.M., Sugawa C., Tran V.R., et al. Presence and density of Helicobacter pylori biofilms in human gastric mucosa in patients with peptic ulcer disease. J Gastrointest Surg. 2006;10:883-889.
-
32.
Yonezawa H., Osaki T., Kurata S., et al. Assessment of in vitro biofilm formation by Helicobacter pylori. J Gastroenterol Hepatol. 2010;25(Suppl. 1):S90-S94.
-
33.
Yonezawa H., Osaki T., Kurata S., et al. Outer membrane vesicles of Helicobacter pylori TK1402 are involved in biofilm formation. BMC Microbiol. 2009;9:197.
-
34.
Williams J.C., McInnis K.A., Testerman T.L. Adherence of Helicobacter pylori to abiotic surfaces is influenced by serum. Appl Environ Microbiol. 2008;74:1255-1258.
-
35.
Attaran B., Falsafi T. Identification of factors associeted with biofilm formation ability in the clinical isolates of Helicobacter pylori. Iran J Biotechnol. 2017;15(1):58-66.
-
36.
Cammarota G., Branca G., Ardito F., et al. Biofilm demolition and antibiotic treatment to eradicate resistant Helicobacter pylori: a clinical trial. Clin Gastroenterol Hepatol. 2010;8:817-820.
-
37.
Fujimoto S., Olaniyi O., Arnqvist A., et al. Helicobacter pylori BabA expression, gastric mucosal injury, and clinical outcome. Clin Gastroenterol Hepatol. 2007;5:49-58.
-
38.
Abadi A., Taghvaei T., Mobarez A., Vaira G., Vaira D. High correlation of babA2-positive strains of Helicobacter pylori with the presence of gastric cancer. Intern Emerg Med. 2013;8(6):497-501.
-
39.
Colbeck J.C., Hansen L.M., Fong J.M., et al. Genotypic profile of the outer membrane proteins BabA and BabB in clinical isolates of Helicobacter pylori. Infect Immun. 2006;74:4375-4378.
-
40.
Bugaytsova J.A., Bjornham O., Chernov Y.A., et al. Helicobacter pylori adapts to chronic infection and gastric disease via pH-responsive BabA-mediated adherence. Cell Host Microbe. 2017;21;376-389.
-
41.
Skoog E.C., Padra M., Aberg A., et al. BabA dependet binding of Helicobacter pylori to human gastric mucins cause aggregation that inhibits proliferation and is regulated via ArsS. Sci Rep. 2017;7:40656.
-
42.
Yamaoka Y., Ojo O., Fujimoto S., et al. Helicobacter pylori outer membrane proteins and gastroduodenal disease. Gut. 2006;55:775781.
-
43.
Ogura K., Maeda S., Nakao M., et al. Virulence factors of Helicobacter pylori responsible for gastric diseases in Mongolian gerbil. J Exp Med. 2000;192(11):1601-1610.
-
44.
Lundstrom A.M., Blom K., Sundaeus V., Bolin I. HpaA shows variable surface localization but the gene expression is similar in different Helicobacter pylori strains. Microb Pathog. 2001;31:243-253.
-
45.
Odenbreit S., Swoboda K., Barwig I., et al. Outer membrane protein expression profile in Helicobacter pylori clinical isolates. Infect Immun. 2009;77(9):3782-3790.
-
46.
Dossumbekova A., Prinz C., Mages J., et al. Helicobacter pylori HopH (OipA) and bacterial pathogenicity: genetic and functional genomic analysis of hopH gene polymorphisms. J Infect Dis. 2006;194(10):1346-1355.
-
47.
Ha N.C., Oh S.T., Sung J.Y., et al. Supramolecular assembly and acid resistance of Helicobacter pylori urease. Nat Struct Biol. 2001;8:505509.
-
48.
Olivera-Severo D., Wassermann G.E., Carlini C.R. Ureases display biological effects independent of enzymatic activity. Is there a connection to diseases caused by urease-producing bacteria? Braz J Med Biol Res. 2006;39(7):851-861.
-
49.
Mine T., Muraoka H., Saika T., Kobayashi I. Characteristics of a clinical isolate of urease-negative Helicobacter pylori and its ability to induce gastric ulcers in Mongolian gerbils. Helicobacter. 2005;10(2):125131.
-
50.
Fan X., Gunasena H., Cheng Z., et al. Helicobacter pylori urease binds to class II MHC on gastric epithelial cells and induces their apoptosis. Immunology. 2000;165:1918-1924.
-
51.
Tanahashi T., Kita M., Kodama T., et al. Cytokine expression and production by purified Helicobacter pylori urease in human gastric epithelial cells. Infect Immun. 2000;68:664-671.
-
52.
Mascellino M.T., Margani M., Oliva A. Helicobacter pylori: determinant and markers of virulence. Dis Markers. 2009;27(3):137156.
-
53.
Atherton J.C., Cao P., Peek R.M.J., et al. Mosaicium in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific vacA types with cytotoxin production and peptic ulceration. J Biol Chem. 1995;28:17771-17777.
-
54.
Cover T.L., Blaser M.J. Purification and characterization of the vacuolating toxin from Helicobacter pylori. J Biol Chem. 1992;267:10570-10575.
-
55.
Rhead J.L., Letley D.P., Mohammadi M., et al. A new Helicobacter pylori vacuolating cytotoxin determinant, the intermediate region, is associated with gastric cancer. Gastroenterology. 2007;133(3):926936.
-
56.
Sinnett C.G., Letley D.P., Narayanan G.L., et al. Helicobacter pylori vacA transcription is genetically-determined and stratifies the level of human gastric inflammation and atrothy. J Clin Pathol. 2016;69:968973.
-
57.
Nukano M., Yahiro K., Yamasaki E., et al. Helicobacter pylori VacA acting through receptor protein tyrosin phosphatase alpha is crucial for CagA phosphorylation in human duodenum carcinoma cell line AZ-521. Dis Model Mech. 2016;9:1473-1481.
-
58.
Shirasaka D. Helicobacter pylori VacA and gastric ulcer. Int J Hematol. 2006;84:316-318.
-
59.
Gebert B., Fischer W., Weiss E., Hoffmann R., Haas R. Helicobacter pylori vacuolating cytotoxin inhibits T lymphocyte activation. Science. 2003;301:1099-1102.
-
60.
Terebiznik M.R., Vazquez C.L., Torbicki K., et al. Helicobacter pylori VacA toxin promotes bacterial intracellular survival in gastric epithelial cells. Infect Immun. 2006;74:6599-6614.
-
61.
Miehlke S., Kirsch C., AghaAmiri K., et al. The Helicobacter pylori vacA sl, ml genotype and cagA is associated with gastric carcinoma in Germany. Int J Cancer. 2000;87:322-327.
-
62.
Miehlke S., Yu J., Schuppler M., et al. Helicobacter pylori vac A, ice A, and cagA status and pattern of gastritis in patients with malignant and benign gastroduodenal disease. Am J Gastroenterol. 2001;96(4):1008-1013.
-
63.
Lopez-Vidal Y., Ponce-de-Leon S., Castillo-Rojas G., Barreto-Zuniga R., Torre-Delgadillo A. High diversity of vacA and cagA Helicobacter pylori genotypes in patients with and without gastric cancer. PLoS One. 2008;3:e3849.
-
64.
Yamaoka Y. Mechanisms of disease: Helicobacter pylori virulence factors. Nat Rev Gastroenterol Hepatol. 2010;7(11):629-641.
-
65.
Basso D., Zambon C.F., Letley D.P., et al. Clinical relevance of Helicobacter pylori cagA and vacA gene polymorphisms. Gastroenterology. 2008;135(1):91-99.
-
66.
Sugimoto M., Yamaoka Y. The association of vacA genotype and Helicobacter pylori-related disease in Latin American and African populations. Clin Microbiol Infect. 2009;15(9):835-842.
-
67.
Uchida T., Nguyen L.T., Takayama A., et al. Analysis of virulence factors of Helicobacter pylori isolated from a Vietnamese population. BMC Microbiol. 2009;9:175.
-
68.
Ogiwara H., Graham D.Y., Yamaoka Y. vacA i-region subtyping. Gastroenterology. 2008;134(4):1267.
-
69.
Odenbreit S., Puls J., Sedlmaier B., et al. Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion. Science. 2000;287:1497-1500.
-
70.
Higashi H., Tsutsumi R., Muto S., et al. SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. Science. 2002;295(5555):683-686.
-
71.
Brandt S., Kwok T., Hartig R., Konig W., Backert S. NF-kappaB activation and potentiation of proinflammatory responses by the Helicobacter pylori CagA protein. Proc Natl Acad Sci U S A. 2005;102(26):9300-9305.
-
72.
Chow W.H., Blaser M.J., Blot W.J., et al. An inverse relation between cagA strains of Helicobacter pylori infection and risk of esophageal and gastric cardia adenocarcinomas. Cancer Res. 1998;58:588590.
-
73.
Roesler B.M., Costa S.C.B., Zeitune J.M.R. Virulence factors of Helicobacter pylori and their relationship with the development of early and advanced distal intestinal type gastric adenocarcinoma. In: Tonino P., editor. Gastritis and Gastric Cancer. New Insights in Gastroprotection, Diagnosis and Treatments. Rijeka Croatia: InTech Publishers; 2011.
-
74.
Jang S., Su H., Blum F.C., et al. Dynamic expansion and contraction of CagA copy number in Helicobacter impact development of gastric disease. MBio. 2017;8(1):pii:e01779-16.
-
75.
Van Doorn L.J., Figueiredo C., Sanna R., et al. Clinical relevance of the cagA, vacA, and iceA status of Helicobacter pylori. Gastroenterology. 1998;115(1):58-66.
-
76.
Yamaoka Y., Kodama T., Gutierrez O., et al. Relationship between Helicobacter pylori iceA, cagA and vacA status and clinical outcome: studies in four different countries. J Clin Microbiol. 1999;37(7):22742279.
-
77.
Schöttker B., Adamu M.A., Weck M.N., Müller H., Brenner H. Helicobacter pylori infection, chronic atrophic gastritis and major cardiovascular events: a population-based cohort study. Atherosclerosis. 2012;220(2):569-574.
-
78.
Shi W.J., Liu W., Zhou X.Y., Ye F., Zhang G.X. Associations of Helicobacter pylori infection and cytotoxin-associated gene A status with autoimmune thyroid diseases: a meta-analysis. Thyroid. 2013;23(10):1294-1300.
-
79.
Hatakeyama M. Helicobacter pylori and gastric carcinogenesis. J Gastroenterol. 2009;44(4):239-248.
-
80.
Yamaoka Y. Mechanisms of disease: Helicobacter pylori virulence factors. Nat Rev Gastroenterol Hepatol. 2011;7(11):629-641.
-
81.
Xu Q., Morgan R.D., Roberts R.J, et al. Functional analysis of iceA1, a CATG-recognizing restriction endonuclease gene in Helicobacter pylori. Nucleic Acids Res. 2002;30(17):3839-3847.
-
82.
Shiota S., Watada M., Osamu M., et al. Helicobacter pylori iceA, clinical outcomes, and correlation with cagA: a meta-analysis. PLoS One. 2012;7(1).
-
83.
Peek R.M., Jr., Tompson S.A., Donahue J.P., et al. 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):531-544.
-
84.
Amjad N., Osman H.A., Razak N.A., et al. Clinical significance of Helicobacter pylori cagA and iceA genotype status. World J Gastroenterol. 2010;16(35):4443-4447.
-
85.
Lu H., Hsu P., Graham D.Y., Yamaoka Y. Duodenal ulcer promoting gene of Helicobacter pylori. Gastroenterology. 2005;128(4):833848.
-
86.
Argent R.H., Burette A., Miendje Deyi V.Y., Atherton J.C. The presence of dupA in Helicobacter pylori is not significantly associated with duodenal ulceration in Belgium, South Africa, China or North America. Clin Infect Dis. 2007;45(9):1204-1206.
-
87.
Schmidt H.M.A., Andres S., Kaakoush N.O., et al. The prevalence of the duodenal ulcer promoting gene (dupA) in Helicobacter pylori isolates varies by ethnic group and is not universally associated with disease development: a case-control study. Gut Pathog. 2009;1(1):5-13.
-
88.
Wang M.Y., Chen C., Gao X.Z., et al. Distribution of Helicobacter pylori virulence markers in patients with gastroduodenal diseases in a region at high risk of gastric cancer. Microb Pathog. 2013:59-60.
-
89.
Gomes L.I., Rocha G.A., Rocha A.M.C., et al. Lack of association between Helicobacter pylori infection with dupA-positive strains and gastroduodenal diseases in Brazilian patients. Int J Med Microbiol. 2008;298(3-4):223-230.
-
90.
Pacheco A.R., Proença-Módena J.L., Sales A.I.L., et al. Involvement of the Helicobacter pylori plasticity region and cag pathogenicity island genes in the development of gastroduodenal diseases. Eur J Clin Microbiol Infect Dis. 2008;27(11):1053-1059.
-
91.
Douraghi M., Mohammadi M., Oghalaie A., et al. dupA as a risk determinant in Helicobacter pylori infection. J Med Microbiol. 2008;57(pt 5):554-562.
-
92.
Shiota S., Matsunari O., Watada M., Hanada K., Yamaoka Y. Systematic review and meta-analysis: the relationship between the Helicobacter pylori dupA gene and clinical outcomes. Gut Pathog. 2010;2(1):13.
-
93.
Gressmann H., Linz B., Ghai R., et al. Gain and loss of multiple genes during the evolution of Helicobacter pylori. PLoS Genet. 2005;1(4):e43.
-
94.
Suerbaum S. Genetic variability within Helicobacter pylori. Int J Med Microbiol. 2000;290:175-181.
-
95.
Nishikawa H., Hayashi T., Arisaka F., et al. Impact of structural polymorphism for the Helicobacter pylori CagA oncoprotein on binding to polarity-regulating kinase PAR1b. Sci Rep. 2016;6:30031.
-
96.
Owen R.E. The genome: viewpoint of biologist. Curr Opin Gastroenterol. 1998;14(Suppl. 1):S1-S3.
-
97.
Garcia-Vallve S., Romeu A., Palau J. Horizontal gene transfer in bacterial and archaeal complete genomes. Genome Res. 2000;110:1719-1725.
-
98.
Valmaseda Perez T., Gisbert J.P., Pajares Garcia J.M. Geographic differences and the role of cagA gene in gastroduodenal diseases associated with Helicobacter pylori infection. Rev Esp Enferm Dig. 2001;93(7):471-480.
-
99.
Berg D.E. Variabilité genomique de Helicobacter pylori: étendue, signification. La Lettre de l’Infectiologue. 1999;3(Suppl. 1):9-15.
-
100.
Figueiredo C., Van Doorn L.J., Nogueira C., et al. Helicobacter pylori genotypes are associated with clinical outcome in Portuguese patients and show a high prevalence of infections with multiple strains. J Gastroenterol. 2001;36(2):128-135.
-
101.
Finger S.A., Velapatiňo B., Kosek M., et al. Effectiveness of enterobacterial repetitive intergenic consensus PCR and random amplified polymorphic DNA fingerprinting for Helicobacter pylori strain differentiation. Appl Environ Microbiol. 2006;72:4713-4716.
-
102.
Daugule I., Rumba I., Engstrand L., Ejderhamn J. Infection with cagApositive and cagA-negative types of Helicobacter pylori among children and adolescents with gastrointestinal symptoms in Latvia. Eur J Clin Microbiol Infect Dis. 2003;22:622-624.
-
103.
Fantry G.T., Zheng Q.X., Darwin P.E., Rosenstein A.H., James S.P. Mixed infection with cagA-positive and cagA-negative strains of Helicobacter pylori. Helicobacter. 1996;1:98-106.
-
104.
Tomasini M.L., Zanussi S., Sozzi M., et al. Heterogeneity of cag genotypes in Helicobacter pylori isolates from human biopsy specimens. J Clin Microbiol. 2003;41:976-980.
-
105.
Camorlinga-Ponce M., Romo C., Gonzalez-Valencia G., et al. Topographical localisation of cagA positive and cagA negative Helicobacter pylori strains in the gastric mucosa; an in situ hybridisation study. J Clin Pathol. 2004;57:822-828.
-
106.
Godoy A.P., Ribeiro M.L., Benvengo Y.H., et al. Analysis of antimicrobial susceptibility and virulence factors in Helicobacter pylori clinical isolates. BMC Gastroenterol. 2003;3:20.
-
107.
Pjurveeva K.V., Lapina T.L., Momynaliev K.T., et al. Genotyping in the clinical practice of patients with duodenum peptic ulcer. Rossijskij zhurnal gastrojenterologii, gepatologii, koloproktologii. 2003;13(3):21-24. Russian.
-
108.
De Francesco V., Margiotta M., Zulla A., et al. Clarithromicyn resistance and Helicobacter pylori genotypes in Italy. J Microbiol. 2006;28:6-13.
-
109.
Mubarak S.А., Adeel Islam А., Abida A.Е. Analysis of Helicobacter pylori antimicrobial susceptibility and virulence genes in gastric mucosal biopsies in the United Arab Emirates. Indian J Gastroenterol. 2007;26:221-224.