Abstract
The aim of this study consisted in an investigation of the variability and functional status of the Helicobacter pylori oipA gene by using a sequencing method and evaluation of the association of oipA functionality with the cagPAI genes and clinical outcomes. The object of the study was 84 samples of H. pylori DNA isolated from antrum biopsies of the gastric mucosa from patients with gastroduodenal diseases. The presence of the cagPAI genes were determined by PCR. The oipA gene status was determined using sequencing reactions. Our results revealed that 79.8% of H. pylori samples had the “on” status of the oipA gene, while the remaining 20.2% of the samples had a nonfunctional gene status. The “on” status of the oipA gene was found to be statistically associated with an increased risk of developing duodenal ulcer compared with superficial gastritis (p < 0.003, OR = 14.5). However, no significant association was observed between the functional oipA status and atrophy gastritis (p < 0.05). The study showed there to be a high frequency of detection of genes of the pathogenicity island among H. pylori DNA samples with an “on” status of the oipA gene. There was a significant correlation between an “on” status of the oipA gene and the presence of all studied cagPAI genes; the highest correlation was found for the cagT and cagM genes. The link between the functional status of the oipA gene and other virulence factors encoded by the pathogenicity island cagPAI is important in the pathogenesis of H. pylori and requires further investigation.
REFERENCES
Burucoa, C. and Axon, A., Epidemiology of Helicobacter pylori infection, Helicobacter, 2017, vol. 22, p. 12403. https://doi.org/10.1111/hel.12403
Yanovich, O., Titov, L., Doroshko, M., Sergeeva, I., and Guzov, S., Helicobacteriosis: Changes of the mucosa in disorder of motor functions (motorics) in the gastroesophagal and duodenogastral zones of the stomach, Dokl. Natl. Acad. Sci. Belarus, 2021, vol. 65, no. 1, pp. 96–102. https://doi.org/10.29235/1561-8323-2021-65-1-96-102
Xu, C., Soyfoo, D., Wu, Y., and Xu, S., Virulence of Helicobacter pylori outer membrane proteins: An updated review, Eur. J. Clin. Microbiol. Infect. Dis., 2020, vol. 39, no. 10, pp. 1821–1830. https://doi.org/10.1007/s10096-020-03948-y
Dossumbekova, A., Prinz, C., Mages, J., Lang, R., Kusters, J.G., Van Vliet, A.H., et al., Helicobacter pylori HopH (OipA) and bacterial pathogenicity: Genetic and functional genomic analysis of hopH gene polymorphisms, J. Infect. Dis., 2006, vol. 194, no. 10, pp. 1346–1355. https://doi.org/10.1086/508426
Chang, W., Yeh, Y., and Sheu, B., The impacts of H. pylori virulence factors on the development of gastroduodenal diseases, J. Biomed. Sci., 2018, vol. 25, no. 1, pp. 68–75. https://doi.org/10.1186/s12929-018-0466-9
Yanovich, O.O., Titov, L.P., and Doroshko, M.V., Distribution of H. pylori pathogenicity factors in patients with gastroduodenal diseases, Gepatol. Gastroenterol., 2018, vol. 2, no. 2, pp. 177–181. https://cyberleninka.ru/article/n/raspredelenie-faktorov-patogennosti-h-pylori-u-patsientov-s-gastroduodenalnymi-zabolevaniyami. Accessed June 12, 2021.
Cover, T., Lacy, D., and Ohi, M., The Helicobacter pylori cag type iv secretion system, Trends Microbiol., 2020, vol. 28, no. 8, pp. 682–695. https://doi.org/10.1016/j.tim.2020.02.004
Sallas, M.L., Dos Santos, M.P., Orcini, W.A., David, É.B., Peruquetti, R.L., Payão, S.L.M., and Rasmussen, L.T., Status (on/off) of oipA gene: Their associations with gastritis and gastric cancer and geographic origins, Arch. Microbiol., 2018, vol. 201, no. 1, pp. 93–97. https://doi.org/10.1007/s00203-018-1580-5
Thorell, K., Lehours, P., and Vale, F., Genomics of Helicobacter pylori, Helicobacter, 2017, vol. 22, p. 12409. https://doi.org/10.1111/hel.12409
Ansari, S. and Yamaoka, Y., Helicobacter pylori virulence factors exploiting gastric colonization and its pathogenicity, Toxins (Basel), 2019, vol. 11, no. 11, p. 677. https://doi.org/10.3390/toxins11110677
Liu, J., He, C., Chen, M., Wang, Z., Xing, C., and 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, vol. 13, no. 1, pp. 555–564. https://doi.org/10.1186/1471-2334-13-555
Chiarini, A., Calà, C., Bonura, C., Gullo, A., Giuliana, G., Peralta, S.F., et al., 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., 2008, vol. 28, no. 5, pp. 437–446. https://doi.org/10.1007/s10096-008-0644-x
Matteo, M.J., Armitano, R.I., Granados, G., Wonaga, A.D., Sánches, C., Olmos, M., and Catalano, M., Helicobacter pylori oipA, vacA and dupA genetic diversity in individual hosts, J. Med. Microbiol., 2010, vol. 59, no. 1, pp. 89–95. https://doi.org/10.1099/jmm.0.011684-0
Oleastro, M., Cordeiro, R., Ferrand, J., Nunes, B., Lehours, P., Carvalho-Oliveira, I., et al., Evaluation of the clinical significance of homB, a novel candidate marker of Helicobacter pylori strains associated with peptic ulcer disease, J. Infect. Dis., 2008, vol. 198, no. 9, pp. 1379–1387. https://doi.org/10.1086/592166
Zhao, Q., Song, C., Wang, K., Li, D., Yang, Y., Liu, D., et al., Prevalence of Helicobacter pylori babA, oipA, sabA, and homB genes in isolates from Chinese patients with different gastroduodenal diseases, Med. Microbiol. Immunol., 2020, vol. 209, no. 5, pp. 565–577. https://doi.org/10.1007/s00430-020-00666-2
Schmidt, H.M., Andres, S., Nilsson, C., Kovach, Z., Kaakoush, N.O., Engstrand, L., et al., The cag PAI is intact and functional but HP0521 varies significantly in Helicobacter pylori isolates from Malaysia and Singapore, Eur. J. Clin. Microbiol. Infect. Dis., 2010, vol. 29, no. 4, pp. 439–451. https://doi.org/10.1007/s10096-010-0881-7
Ando, T., Peek, R.M., Pride, D., Levine, S.M., Takata, T., Lee, Y.C., et al., Polymorphisms of Helicobacter pylori HP0638 reflect geographic origin and correlate with cagA status, J. Clin. Microbiol., 2002, vol. 40, no. 1, pp. 239–246. https://doi.org/10.1128/jcm.40.1.239-246.2002
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., and 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, pp. 48–54. https://doi.org/10.1186/s12885-018-5249-x
Markovska, R., Boyanova, L., Yordanov, D., Gergova, G., and Mitov, I., Helicobacter pylori oipA genetic diversity and its associations with both disease and cagA, vacA s, m, and i alleles among Bulgarian patients, Diagn. Microbiol. Infect. Dis., 2011, vol. 71, no. 4, pp. 335–340.
Yamaoka, Y., Helicobacter pylori outer membrane proteins and gastroduodenal disease, Gut, 2006, vol. 55, no. 6, pp. 775–781. https://doi.org/10.1136/gut.2005.083014
Kauser, F., Hussain, M.A., Ahmed, I., Ahmad, N., Habeeb, A., Khan, A.A., and Ahmed, N., Comparing genomes of Helicobacter pylori strains from the high-altitude desert of Ladakh, India, J. Clin. Microbiol., 2005, vol. 43, no. 7, p. 3586. https://doi.org/10.1128/jcm.43.7.3586.2005
Farzi, N., Yadegar, A., Aghdaei, H., Yamaoka, Y., and Zali, M., Genetic diversity and functional analysis of oipA gene in association with other virulence factors among Helicobacter pylori isolates from Iranian patients with different gastric diseases, Infect., Genet. Evol., 2018, vol. 60, pp. 26–34. https://doi.org/10.1016/j.meegid.2018.02.017
Lehours, P., Ménard, A., Dupouy, S., Bergey, B., Richy, F., Zerbib, F., et al., Evaluation of the association of nine Helicobacter pylori virulence factors with strains involved in low-grade gastric mucosa-associated lymphoid tissue lymphoma, Infect. Immun., 2004, vol. 72, no. 2, pp. 880–888. https://doi.org/10.1128/iai.72.2.880-888.2004
Horridge, D., Begley, A., Kim, J., Aravindan, N., Fan, K., and Forsyth, M., Outer inflammatory protein a (OipA) of Helicobacter pylori is regulated by host cell contact and mediates CagA translocation and interleukin-8 response only in the presence of a functional cag pathogenicity island type IV secretion system, Pathog. Dis., 2017, vol. 75, no. 8, pp. 113–123. https://doi.org/10.1093/femspd/ftx113
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
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Translated by V. Mittova
APPENDIX
APPENDIX
Appendix to the article by O.O. Yanovich, L.P. Titov, and M.V. Doroshko “Genetic Diversity and Functional Status of the oipA Gene of Helicobacter pylori. Its Association with Genes of the Pathogenicity Island in Patients with Gastroduodenal Diseases in the Republic of Belarus.”
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Yanovich, O.O., Titov, L.P. & Doroshko, M.V. Genetic Diversity and Functional Status of the oipA Gene of Helicobacter pylori. Its Association with Genes of the Pathogenicity Island in Patients with Gastroduodenal Diseases in the Republic of Belarus. Mol. Genet. Microbiol. Virol. 37, 173–178 (2022). https://doi.org/10.3103/S0891416822040097
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DOI: https://doi.org/10.3103/S0891416822040097