Genetic polymorphisms of helicobacter pylori clinical isolates in St. Petersburg, Russia

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Abstract

Introduction. Helicobacter pylori was proved to be the principal causative agent of gastroduodenal disorders in human. Although Russian Federation is among the countries with a high prevalence of H. pylori infection (60–90%), currently there is a very limited number of studies evaluating H. pylori genotypes in Russia. Objective. Based on the assessment of virulence-associated cagA, oipA, and vacA genes, our study was aimed to determine H. pylori genotypes associated with the clinical outcomes in patients with H. pylori infection in St. Petersburg, Northwest Russia. Materials and methods. Using PCR for the detection of cagA, oipA, and vacA s, m, i allelic variants, we analyzed 61 H. pylori isolates isolated and cultured from biopsies collected during endoscopy of patients with chronic gastritis (G), duodenal ulcer (DU), and gastric cancer (GC). Results. The genetic diversity of H. pylori clinical isolates has been revealed (HGDI 0.88): 41 (67%) of 61 H. pylori isolates were cagA-positive, 38 (62%) — oipA-positive. The proportions of cagA+ isolates differed in patients with G (56.7%) and DU (80.9%) (p = 0.06). The s, m, and i allelic variants of the vacA gene were detected in all strains, although the vacA s1 allele was significantly dominant in patients with DU (95.2%) rather than with G (64.9%) (p = 0.01). The vacA alleles m1 and i1 in the isolates from patients with G and DU were found in almost equal proportions: 45.9% and 42.8% for m1 allele, 45.9% and 47.6% for i1 allele, respectively. Seven isolates (11.5%) were positive for different mixed combinations of vacA alleles s, m, and i. Noteworthy, all vacA s2 strains were cagA-negative and had the m2 allele. OipA+ strains were found in almost equal proportions in patients with G (62.2%) and DU (57.1%) (p = 0.71). All three cagA- and oipA-positive isolates from patients with GC carried vacA s1/m1/i1 alleles. Different combinations of virulence-associated determinants constituted 17 genetic profiles. The most common combined genotype cagA+/oipA+/vacA s1/m1/i1 comprised 18 (29.5%) H. pylori isolates. Conclusion. We have determined predominant genotypes in the H. pylori population in the Northwest of Russia. The significant association between vacA s1 genotype of the pathogen and clinical manifestations of H. pylori infection has been established in our study.

About the authors

A. V. Svarval

St. Petersburg Pasteur Institute

Email: alena.svarval@mail.ru
ORCID iD: 0000-0001-9340-4132

PhD (Medicine), Senior Researcher, Head of the Pathogens Identification Laboratory

Russian Federation, 197101, St. Petersburg, Mira str., 14

Daria A. Starkova

St. Petersburg Pasteur Institute

Email: dariastarkova13@gmail.com
ORCID iD: 0000-0003-3199-8689

PhD (Biology), Senior Researcher of the Pathogens Identification Laboratory, Researcher of the Laboratory of Molecular Epidemiology and Evolutionary Genetics

Russian Federation, 197101, St. Petersburg, Mira str., 14

R. S. Ferman

St. Petersburg Pasteur Institute

Email: laborimmun@mail.ru
ORCID iD: 0000-0001-7661-3725

Junior Researcher, Pathogens Identification Laboratory

Russian Federation, 197101, St. Petersburg, Mira str., 14

O. V. Narvskaya

St. Petersburg Pasteur Institute; St. Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Health of Russia

Author for correspondence.
Email: onarvskaya@gmail.com
ORCID iD: 0000-0002-0830-5808

PhD, MD (Medicine), Professor, Leading Researcher, Laboratory of Molecular Epidemiology and Evolutionary Genetics, Academic Adviser

Russian Federation, 197101, St. Petersburg, Mira str., 14; St. Petersburg

References

  1. Ахтереева А.Р., Давидюк Ю.Н., Файзуллина Р.А., Ивановская К.А., Сафин А.Г., Сафина Д.Д., Абдулхаков С.Р. Распространенность генотипов Helicobacter pylori у пациентов с гастродуоденальной патологией в Казани // Казанский медицинский журнал. 2017. Т. 98, № 5. C. 723–728. [Akhtereeva A.R., Davidyuk Y.N., Faizullina R.A., Ivanovskaya K.A., Safin A.G., Safina D.D., Abdulkhakov S.R. Prevalence of Helicobacter pylori genotypes in patients with gastroduodenal pathology in Kazan. Kazanskiy meditsinskiy zhurnal = Kazan Medical Journal, 2017, vol. 98, no. 5, pp. 723–728. (In Russ.)] doi: 10.17750/KMJ2017-723
  2. Сорокин В.М., Писанов Р.В., Водопьянов А.С., Голубкина Е.В., Березняк Е.А. Сравнительный анализ генотипов штаммов Helicobacter pylori в Ростовской и Астраханской области // Медицинский вестник Юга России. 2018. Т. 9, № 4. С. 81–86. [Sorokin V.M., Pisanov R.V., Vodop’janov A.S., Golubkina E.V., Bereznjak E.A. Comparative analysis of genotypes of Helicobacter pylori strains in the Rostov and Astrakhan regions. Medicinskij vestnik Yuga Rossii = Medical Herald of the South of Russia, 2018, vol. 9, no. 4, pp. 81–86. (In Russ.)] doi: 10.21886/2219-8075-2018-9-4-81-86
  3. Щанова Н.О., Прохорова Л.В. Возможности повышения эффективности эрадикации Helicobacter pylori у больных язвенной болезнью желудка и двенадцатиперстной кишки // Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2016. № 2. С. 11–18. [Schanova N.O., Prokhorova L.V. Improvement of Helicobacter pylori eradication efficacy at stomach and duodenum peptic ulcers. Rossiiskii zhurnal gastroenterologii, gepatologii, koloproktologii = Russian Journal of Gastroenterology, Hepatology, Coloproctology, 2016, no. 2, pp. 11–18. (In Russ.)]
  4. Almeida N., Donato M.M., Romãozinho J.M., Luxo C., Cardoso O., Cipriano M.A., Marinho C., Fernandes A., Sofia C. Correlation of Helicobacter pylori genotypes with gastric histopathology in the central region of a South-European country. Dig. Dis. Sci., 2015, vol. 60, no. 1, pp. 74–85. doi: 10.1007/s10620-014-3319-8
  5. Atherton J.C., Cao P., Peek R.M., Tummuru M.K., Blaser M.J., Cover T.L. Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific vacA types with cytotoxin production and peptic ulceration. J. Biol. Chem., 1995, vol. 270, pp. 17771–17777. doi: 10.1074/jbc.270.30.17771
  6. Braga L.L.B.C., Batista M.H.R., de Azevedo O.G.R., da Silva Costa K.C., Gomes A.D., Rocha G.A., Queiroz D.M.M. OipA “on” status of Helicobacter pylori is associated with gastric cancer in North-Eastern Brazil. BMC Cancer, 2019, vol. 19, no. 1: 48. doi: 10.1186/s12885-018-5249-x
  7. Chiarini A., Calà C., Bonura C., Gullo A., Giuliana G., Peralta S., D’Arpa F., Giammanco A. Prevalence of virulence-associated genotypes of Helicobacter pylori and correlation with severity of gastric pathology in patients from western Sicily, Italy. Eur. J. Clin. Microbiol. Infect. Dis., 2009, vol. 28, pp. 437–446. doi: 10.1007/s10096-008-0644-x
  8. Da Costa D.M., Pereira Edos S., Rabenhorst S.H. What exists beyond cagA and vacA? Helicobacter pylori genes in gastric diseases. World J. Gastroenterol., 2015, vol. 21, no. 37, pp. 10563–10572. doi: 10.3748/wjg.v21.i37.10563
  9. De Brito B.B., da Silva F.A.F., Soares A.S., Pereira V.A., Santos M.L.C., Sampaio M.M., Neves P.H.M., de Melo F.F. Pathogenesis and clinical management of Helicobacter pylori gastric infection. World. J. Gastroenterol., 2019, vol. 25, no. 37, pp. 5578–5589. doi: 10.3748/wjg.v25.i37.5578
  10. Diab M., Shemis M., Gamal D., El-Shenawy A., El-Ghannam M., El-Sherbini E. Helicobacter pylori Western cagA genotype in Egyptian patients with upper gastrointestinal disease. EJMHG, 2018, vol. 19, no. 4, pp. 297–300. doi: 10.1016/j.ejmhg.2018.06.003
  11. Foegeding N.J., Caston R.R., McClain M.S., Ohi M.D., Cover T.L. An overview of Helicobacter pylori VacA toxin biology. Toxins (Basel), 2016, vol. 8, no. 6: e173. doi: 10.3390/toxins8060173
  12. Heikkinen M., Mayo K., Mégraud F., Vornanen M., Marin S., Pikkarainen P., Julkunen R. Association of CagA-positive and CagA-negative Helicobacter pylori strains with patients’ symptoms and gastritis in primary care patients with functional upper abdominal complaints. Scand. J. Gastroenterol., 1998, vol. 33, no. 1, pp. 31–38. doi: 10.1080/00365529850166176
  13. Imkamp F., Lauener F.N., Pohl D., Lehours P., Vale F.F., Jehanne Q., Zbinden R., Keller P.M., Wagner K. Rapid characterization of virulence determinants in Helicobacter pylori isolated from non-atrophic gastritis patients by next-generation sequencing. J. Clin. Med., 2019, vol. 8, no. 7: 1030. doi: 10.3390/jcm8071030
  14. Inagaki T., Nishiumi S., Ito Y., Yamakawa A., Yamazaki Y., Yoshida M., Azuma T. Associations between cagA, vacA, and the clinical outcomes of Helicobacter pylori infections in Okinawa, Japan. Kobe J. Med. Sci., 2017, vol. 63, no. 2, pp. 58–67.
  15. Kamogawa-Schifter Y., Yamaoka Y., Uchida T., Beer A., Tribl B., Schöniger-Hekele M., Trauner M., Dolak W. Prevalence of Helicobacter pylori and its CagA subtypes in gastric cancer and duodenal ulcer at an Austrian tertiary referral center over 25 years. PLoS One, 2018, vol. 13, no. 5: e0197695. doi: 10.1371/journal.pone.0197695
  16. Liu J., He C., Chen M., Wang Z., Xing C., Yuan Y. Association of presence/absence and on/off patterns of Helicobacter pylori oipA gene with peptic ulcer disease and gastric cancer risks: a meta-analysis. BMC Infect. Dis., 2013, 13: 555. doi: 10.1186/1471-2334-13-555
  17. Miehlke S., Kirsch C., Agha-Amiri K., Günther T., Lehn N., Malfertheiner P., Stolte M., Ehninger G., Bayerdörffer E. The Helicobacter pylori vacA s1, m1 genotype and cagA is associated with gastric carcinoma in Germany. Int. J. Cancer, 2000, vol. 87, no. 3, pp. 322–327.
  18. Momynaliev K., Smirnova O., Kudryavtseva L., Govorun V. Helicobacter pylori genotypes in Russia. Eur. J. Clin. Microbiol. Infect. Dis., 2003, vol. 22, no. 9, pp. 573–574. doi: 10.1007/s10096-003-0987-2
  19. Muhsen K., Sinnereich R., Beer-Davidson G., Nassar H., Abu Ahmed W., Cohen D., Kark J.D. Correlates of infection with Helicobacter pylori positive and negative cytotoxin-associated gene A phenotypes among Arab and Jewish residents of Jerusalem. Epidemiol. Infect., 2019, vol. 147: e276. doi: 10.1017/S0950268819001456
  20. Mukhopadhyay A.K., Kersulyte D., Jeong J.Y., Datta S., Ito Y., Chowdhury A., Santra A., Bhattacharya S.K., Azuma T., Nair G.B., Berg D.E. Distinctiveness of genotypes of Helicobacter pylori in Calcutta, India. J. Bacteriol., 2000, vol. 182, no. 11, pp. 3219–3227. doi: 10.1128/jb.182.11.3219-3227.2000
  21. Nguyen L.T., Uchida T., Murakami K., Fujioka T., Moriyama M. Helicobacter pylori virulence and the diversity of gastric cancer in Asia. J. Med. Microbiol., 2008, vol. 57, no. 12, pp. 1445–1453. doi: 10.1099/jmm.0.2008/003160-0
  22. Rahman M., Mukhopadhyay A.K., Nahar S., Datta S., Ahmad M.M., Sarker S., Masud I.M., Engstrand L., Albert M.J., Nair G.B., Berg D.E. DNA-level characterization of Helicobacter pylori strains from patients with overt disease and with benign infections in Bangladesh. J. Clin. Microbiol., 2003, vol. 41, no. 5, pp. 2008–2014. doi: 10.1128/jcm.41.5.2008-2014.2003
  23. Rhead J.L., Letley D.P., Mohammadi M., Hussein N., Mohagheghi M.A., Eshagh Hosseini M., Atherton J.C. A new Helicobacter pylori vacuolating cytotoxin determinant, the intermediate region, is associated with gastric cancer. Gastroenterology, 2007, vol. 133, no. 3, pp. 926–936. doi: 10.1053/j.gastro.2007.06.056
  24. Tanih N.F., McMillan M., Naidoo N., Ndip L.M., Weaver L.T., Ndip R.N. Prevalence of Helicobacter pylori vacA, cagA and iceA genotypes in South African patients with upper gastrointestinal diseases. Acta Trop., 2010, vol. 116, no. 1, pp. 68–73. doi: 10.1016/ j.actatropica.2010.05.011
  25. Tsukanov V.V., Butorin N.N., Maady A.S., Shtygasheva O.V., Amelchugova O.S., Tonkikh J.L., Fassan M., Rugge M. Helicobacter pylori infection, intestinal metaplasia, and gastric cancer risk in Eastern Siberia. Helicobacter, 2011, vol. 16, no. 2, pp. 107–112. doi: 10.1111/j.1523-5378.2011.00827.x
  26. Tumurru M.K., Cover T.L., Blaser M.J. Cloning and expression of a high-molecular mass major antigen of Helicobacter pylori: evidence of linkage to cytotoxin production. Infect. Immun., 1993, vol. 61, pp. 1799–1809.
  27. Uchida T., Miftahussurur M., Pittayanon R., Vilaichone R.K., Wisedopas N., Ratanachu-Ek T., Kishida T., Moriyama M., Yamaoka Y., Mahachai V. Helicobacter pylori Infection in Thailand: A Nationwide Study of the CagA Phenotype. PLoS One, 2015, vol. 10, no. 9: e0136775. doi: 10.1371/journal.pone.0136775
  28. Van Doorn L.J., Figueiredo C., Mégraud F., Pena S., Midolo P., Queiroz D.M., Carneiro F., Vanderborght B., Pegado M.D., Sanna R., De Boer W., Schneeberger P.M., Correa P., Ng E.K., Atherton J., Blaser M.J., Quint W.G. Geographic distribution of vacA allelic types of Helicobacter pylori. Gastroenter., 1999, vol. 116, no. 4, pp. 823–830. doi: 10.1016/s0016-5085(99)70065-x
  29. Versalovic J., Koeuth T., Lupski J.R. Distribution of repetitive DNA sequences in Eubacteria and application to fingerprinting of bacterial genomes. Nucleic Acids Res., 1991, vol. 19, pp. 6823–6831. doi: 10.1093/nar/19.24.6823
  30. Yamaoka Y., Kodama T., Gutierrez O., Kim J.G., Kashima K., Graham D.Y. Relationship between Helicobacter pylori iceA, cagA, and vacA status and clinical outcome: studies in four different countries. J. Clin. Microbiol., 1999, vol. 37, pp. 2274–2279.

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Copyright (c) 2022 Svarval A.V., Starkova D.A., Ferman R.S., Narvskaya O.V.

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