Helicobacter pylori infection: a modern view on virulence and pathogenicity factors

T.V. Sorokman, N.O. Popelyuk, D.I. Kolesnik


The review considers the main pathogenicity factors of Helicobacter pylori: colonization factors, persistence factors and disease-causing factors. Modern data on mechanism of action, genotypic bases and significance in pathogenesis of diseases are presented.


Helicobacter pylori; ureA/B, VacA, CagA, flaA, flaB, flaЕ, BabA, SabA, AlpA, AlpB, HopZ, Le, LPS factors; review


Calvet X., Ramırez Lazaro M.J., Lehours P., Megraud F. Diagnosis and epidemiology of Helicobacter pylori infection. Helicobacter. 2013. 18(Suppl. 1). 5e11.

Shadrin O.G., Zaytceva N.E., Garicheva T.A. Нelicobacter pylori among children: modern approaches to the diagnosis and ways to optimize therapy. Sovremennaya Pediatriya. 2014. 5(61). Р. 119-127. doi: 10.15574/SP.2014.61.119.

Marshall B.J., Warren J.R. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet. 1984. 1. Р. 1311-1315.

Blaser M.J., Atherton J.C. Helicobacter pylori persistence: biology and disease. J. Clin. Invest. 2004. 113. Р. 321-333.

Yamaoka Y. Mechanisms of disease: Helicobacter pylori virulence factors. Nat. Rev. Gastroenterol. Hepatol. 2010. 7(11). Р. 629-41. doi: 10.1038/nrgastro.2010.154.

Peek R.M., Crabtree J.E. Helicobacter infection and gastric neoplasia. J. Pathol. 2006. 208. Р. 233-248. doi: 10.1002/path.1868.

Jemal A., Siegel R., Xu J., Ward E. Cancer Statistics, 2010. CA Cancer J. Clin. 2010 Sep-Oct. 60(5). Р. 277-300. doi: 10.3322/caac.20073.

Suerbaum S., Achtman M. Evolution of Helicobacter pylori: the role of recombination. Trends Microbiol. 1999 May. 7(5). Р. 182-4.

Smet A., Yahara K., Rossi M. et al. Macroevolution of gastric Helicobacter species unveils interspecies admixture and time of divergence. 11ISME J. 2018. 12(10). Р. 2518-2531. doi: 10.1038/s41396-018-0199-5.

Huson D.H., Bryant D. Application of phylogenetic networks in evolutionary studies. Mol. Biol. Evol. 2006. 23. Р. 254-267. doi: 10.1093/molbev/msj030.

Moodley Y., Linz B., Bond R.P. et al. Age of the association between Helicobacter pylori and man. PLoS Pathog. 2012. 8(5). e1002693. doi: 10.1371/journal.ppat.1002693.

Sarem M., Corti R. Role of Helicobacter pylori coccoid forms in infection and recrudescence. Gastroenterol. Hepatol. 2016. 39(1). Р. 28-35. doi: 10.1016/j.gastrohep.2015.04.009.

Reshetnyak V.I., Reshetnyak T.M. Significance of dormant forms of Helicobacter pylori in ulcerogenesis. World J. Gastroenterol. 2017. 23(27). Р. 4867-4878. doi: 10.3748/wjg.v23.i27.4867.

Hirukawa S., Sagara H., Kaneto S. et al. Characterization of morphological conversion of Helicobacter pylori under anaerobic conditions. Microbiol. Immunol. 2018. 62(4). Р. 221-228. doi: 10.1111/1348-0421.12582.

Cellini L. Helicobacter pylori: a chameleon-like approach to life. World J. Gastroenterol. 2014, May 21. 20(19). Р. 5575-82. doi: 10.3748/wjg.v20.i19.5575.

West A.P., Millar M.R., Tompkins D.S. Effect of physical environment on survival of Helicobacter pylori. Journal of Clinical Pathology. 1992. 45. Р. 228-231.

Kamboj A.K., Cotter T.G., Oxentenko A.S. Helicobacter pylori: The Past, Present, and Future in Management. Mayo Clin. Proc. 2017. 92(4). Р. 599-604. doi: 10.1016/j.mayocp.

Lopes A.I., Vale F.F., Oleastro M. Helicobacter pylori infection — recent developments in diagnosis. World J. Gastroenterol. 2014, Jul 28. 20(28). Р. 9299-313. doi: 10.3748/wjg.v20.i28.9299.

Camilo V., Sugiyama T., Touati E. Pathogenesis of Helicobacter pylori infection. Helicobacter. 2017. 22 Suppl 1. doi: 10.1111/hel.12405.

Matsuo Y., Kido Y., Yamaoka Y. Helicobacter pylori Outer Membrane Protein-Related Pathogenesis. Toxins (Basel). 2017, Mar 11. 9(3). pii: E101. doi: 10.3390/toxins9030101.

Grahama D.Y., Miftahussurur M. Helicobacter pylori urease for diagnosis of Helicobacter pylori infection: A mini review. J. Adv. Res. 2018. 13. Р. 51-57. doi: 10.1016/j.jare.2018.01.006.

Koumi A., Filippidis T., Leontara V. et al. Detection of Helicobacter pylori: a faster urease test can save resources. World J. Gastroenterol. 2011. 17(3). Р. 349-353. doi: 10.3748/wjg.v17.i3.349.

Schirm M., Soo E.C., Aubry A.J. et al. Structural, genetic and functional characterization of the flagellin glycosylation process in Helicobacter pylori. Mol. Microbiol. 2003 Jun. 48(6). Р. 1579-92.

Yan J., Liang S.H., Mao Y.F., Li L.W., Li S.P. Construction of expression systems for flaA and flaB genes of Helicobacter pylori and determination of immunoreactivity and antigenicity of recombinant proteins.World J. Gastroenterol. 2003. 9(10). Р. 2240-50. doi: 10.3748/wjg.v9.i10.2240.

Thorell K., Lehours P., Vale F.F. Genomics of Helicobacter pylori. Helicobacter. 2017. 22 Suppl 1. doi: 10.1111/hel.12409.

Berthenet E., Sheppard S., Vale F.F. Recent «omics» advances in Helicobacter pylori. Helicobacter. 2016. 21 Suppl 1. Р. 14-8. doi: 10.1111/hel.12334.

Kojima K.K., Furuta Y., Yahara K. et al. Population Evolution of Helicobacter pylori through Diversification in DNA Methylation and Interstrain Sequence Homogenization. Mol. Biol. Evol. 2016 Nov. 33(11). Р. 2848-2859. doi: 10.1093/molbev/msw162.

Bubendorfer S., Krebes J., Yang Hage et al. Genome-wide analysis of chromosomal import patterns after natural transformation of Helicobacter pylori. Nat. Commun. 2016. 7. 11995. doi: 10.1038/ncomms11995.

Ansari S., Yamaoka Y. Helicobacter pylori BabA in adaptation for gastric colonization. World J. Gastroenterol. 2017. 23. Р. 4158-4169. doi: 10.3748/wjg.v23.i23.4158.

Hage N., Howard T., Phillips C. et al. Structural basis of Lewis(b) antigen binding by the Helicobacter pylori adhesin BabA. Falcone FH. Sci. Adv. 2015 Aug. 1(7). e1500315. doi: 10.1126/sciadv.1500315.

Kato S., Osaki T., Kamiya S., Zhang X.S., Blaser M.J. Helicobacter pylori sabA gene is associated with iron deficiency anemia in childhood and adolescence. PLoS One. 2017, Aug 30. 12(8). e0184046. doi: 10.1371/journal.pone.0184046.

Benktander J., Barone A., Johansson M.M., Teneberg S. Helicobacter pylori SabA binding gangliosides of human stomach. Virulence. 2018, Dec 31. 9(1). Р. 738-751. doi: 10.1080/21505594.2018.1440171.

Borhani K., Mohabati Mobarez A., Khabiri A.R. et al. Inhibitory effects of rHP-NAP IgY against Helicobacter pylori attachment to AGS cell line. Microb. Pathog. 2016 Aug. 97. Р. 231-5. doi: 10.1016/j.micpath.2016.06.004.

Mendoza J.A., Weinberger K.K., Swan M.J. The Hsp60 protein of helicobacter pylori displays chaperone activity under acidic conditions. Biochem. Biophys. Rep. 2016, Nov 27. 9. Р. 95-99. doi: 10.1016/j.bbrep.2016.11.011.

Yonezawa H., Osaki T., Fukutomi T. et al. Diversification of the AlpB Outer Membrane Protein of Helicobacter pylori Affects Biofilm Formation and Cellular Adhesion. J. Bacteriol. 2017, Feb 28. 199(6). e00729-16. doi: 10.1128/JB.00729-1636.

Kennemann L., Brenneke B., Andres S. et al. In vivo sequence variation in HopZ, a phase-variable outer membrane protein of Helicobacter pylori. Infect. Immun. 2012 Dec. 80(12). Р. 4364-73. doi: 10.1128/IAI.00977-12.

Paraskevopoulou V., Artiaga V.G., Rowlinson R. et al. Introduction of a C-terminal hexa-lysine tag increases thermal stability of the LacDiNac binding adhesin (LabA) exodomain from Helicobacter pylori. Protein. Expr. Purif. 2019, Jul 1. 163. 105446. doi: 10.1016/j.pep.2019.105446.

Markovska R., Boyanova L., Yordanov D. et al. Status of Helicobacter pylori cag pathogenicity island (cagPAI) integrity and significance of its individual genes. Infect. Genet. Evol. 2018 Apr. 59. Р. 167-171. doi: 10.1016/j.meegid.2018.02.009.

Tohidpour A. CagA-mediated pathogenesis of Helicobacter pylori. Microb. Pathog. 2016 Apr. 93. Р. 44-55. doi: 10.1016/j.micpath.2016.01.00.

Backert S., Haas R., Gerhard M., Naumann M. The Helicobacter pylori Type IV Secretion System Encoded by the cag Pathogenicity Island: Architecture, Function, and Signaling. Curr. Top. Microbiol. Immunol. 2017. 413. Р. 187-220. doi: 10.1007/978-3-319-75241-9_8.

Salih B.A., Guner A., Karademir A. et al. Evaluation of the effect of cagPAI genes of Helicobacter pylori on AGS epithelial cell morphology and IL-8 secretion. Antonie Van Leeuwenhoek. 2014 Jan. 105(1). Р. 179-89. doi: 10.1007/s10482-013-0064-5.

Zhu S., Soutto M., Chen Z. et al. Helicobacter pylori-induced cell death is counteracted by NF-κB-mediated transcription of DARPP-32. Gut. 2017 May. 66(5). Р. 761-762. doi: 10.1136/gutjnl-2016-312141.

Sanabria-Valentín E., Colbert M.T., Blaser M.J. Role of futC slipped strand mispairing in Helicobacter pylori Lewisy phase variation. Microbes Infect. 2007 Nov-Dec. 9(14–15). Р. 1553-60. doi: 10.1016/j.micinf.2007.08.011.

Li H., Liao T., Debowski A.W. et al. Lipopolysaccharide Structure and Biosynthesis in Helicobacter pylori. Helicobacter. 2016 Dec. 21(6). Р. 445-461. doi: 10.1111/hel.12301.

Baskerville A., Newell D.G. Naturally occurring chronic gastritis and C. pylori infection in the rhesus monkey: a potential model for gastritis in man. Gut. 1988 Apr. 29(4). Р. 465-472. doi: 10.1136/gut.29.4.465.

Altman E., Harrison B.A., Hirama T. et al. Characteri­zation of murine monoclonal antibodies against Helicobacter pylori lipopolysaccharide specific for Lex and Ley blood group determinants. Biochem. Cell. Biol. 2005 Oct. 83(5). Р. 589-96. doi:10.1139/o05-052.

Amano K., Hayashi S., Kubota T., Fujii N., Yokota S. Reactivities of Lewis antigen monoclonal antibodies with the lipopolysaccharides of Helicobacter pylori strains isolated from patients with gastroduodenal diseases in Japan. Clin. Diagn. Lab. Immunol. 1997. 4. Р. 540-544.

Appelmelk B.J., Martin S.L., Monteiro M.A. et al. Phase variation in Helicobacter pylori lipopolysaccharide due to changes in the lengths of poly(C) tracts in alpha3-fucosyltransferase genes. Infect. Immun. 1999. 67. Р. 5361-5366.

Appelmelk B.J., Simoons-Smit I., Negrini R. et al. Potential role of molecular mimicry between Helicobacter pylori lipopolysaccharide and host Lewis blood group antigens in autoimmunity. Infect. Immun. 1996. 64. Р. 2031-2040.

Chauhan N., Tay A.C.Y., Marshall B.J., Jain U. Helicobacter pylori VacA, a distinct toxin exerts diverse functionalities in numerous cells: An overview. Helicobacter. 2019 Feb. 24(1). e12544. doi: 10.1111/hel.12544.

Junaid M., Linn A.K., Javadi M.B. et al. Toxicon Vacuolating cytotoxin A (VacA) — A multi-talented pore-forming toxin from Helicobacter pylori. 2016 Aug. 118. Р. 27-35. doi: 10.1016/j.toxicon.2016.04.037.

Yahiro K., Hirayama T., Moss J., Noda M. Helicobacter pylori VacA toxin causes cell death by inducing accumulation of cytoplasmic connexin 43Cell Death Dis. 2015 Nov. 6(11). e1971.12. doi: 10.1038/cddis.2015.329.

Chang Y.H., Wang L., Lee M.S. et al. Genotypic characterization of Helicobacter pylori cagA and vacA from biopsy specimens of patients with gastroduodenal diseases. Mt. Sinai. J. Med. 2006. 73. Р. 622-626.

Trang T.T., Binh T.T., Yamaoka Y. Relationship between vacA Types and Development of Gastroduodenal Diseases. To­xins. 2016. 8(6). Р. 182. doi: 10.3390/toxins8060182.

Perez-Perez G.I., Peek R.M. Jr, Atherton J.C. et al. Detection of anti-VacA antibody responses in serum and gastric juice samples using type s1/m1 and s2/m2 Helicobacter pylori VacA antigens. Clin. Diagn. Lab. Immunol. 1999. 6(4). Р. 489-93.

Wang D., Li Q., Gong Y., Yuan Y. The association between vacA or cagA status and eradication outcome of Helicobacter pylori infection: A meta-analysis. PLoS One. 2017. 12(5). e0177455. doi: 10.1371/journal.pone.0177455.

Copyright (c) 2019 ACTUAL INFECTOLOGY

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.


© Publishing House Zaslavsky, 1997-2020


   Seo анализ сайта