All Issue

2022 Vol.52, Issue 4 Preview Page

Original Article

Regulation in the Expression of Virulence Factors of Helicobacter pylori by the Interaction between AGS Cells and H. pylori
Yu-Ri Kim1
,
Wongwarut Boonyanugomol2
,
Won-jun An13
,
Trinh Minh Phuong13
,
Jin-Sik Park1
,
Min-Kyoung Shin1345
,
Seung-Chul Baik14
,
Woo-Kon Lee145
,
Myung-Je Cho145
,
Hyung-Lyun Kang145*
,
Myunghwan Jung1345*
1Department of Microbiology College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea
2Department of Sciences and Liberal Arts, Mahidol University, Amnatcharoen Campus, Amnatcharoen, Thailand
3BK21 Center for Human Resource Development in the Bio-Health Industry, Department of Convergence Medical Science, Gyeongsang National University, Jinju 52727, Republic of Korea
4Institute of Health Science, Gyeongsang National University, Jinju 52727, Republic of Korea
5Research Institute of Life Science, Gyeongsang National University, Jinju 52828, Republic of Korea
*gangssi@gnu.ac.kr
*mjung@gnu.ac.kr
31 December 2022. pp. 160-169
PDF XML Citation
Abstract

Helicobacter pylori (H. pylori) was defined as a Class 1 pathogenic carcinogen by WHO causing chronic inflammation in the stomach, thereby increasing the risk of gastric cancer. Various virulence factors are involved in the mechanism of gastric cancer caused by H. pylori infection. These virulence factors usually show different expression levels depending on the environment of H. pylori, which can affect the risk of gastric cancer. In this study, the differences in the expression levels of major virulence factors of H. pylori depending on the environment were investigated by comparing expression levels of H. pylori cultured with AGS or alone. As a result, there was no difference in the expression of adhesins of alpA, sabA, and babA even after co-culture with AGS cells. In addition, the co-culture environment did not induce a difference in the expression levels of flaA and ureB. On the other hand, H. pylori co-cultured with AGS cells showed low expression levels of cagA, groEL, and oipA and high expression of vacA compared to H. pylori cultured alone. Our results suggest that not only the presence or absence of virulence factor genes but also differences in expression levels should be considered when evaluating the risk of gastric cancer after H. pylori infection based on the virulence factors.

Keywords
H. pylori
Virulence factors
Gene expression
AGS cells
References
1
Blaser MJ, Atherton JC. Helicobacter pylori persistence: biology and disease. J Clin Invest 2004;113:321-33. 10.1172/JCI2092514755326PMC324548
2
Malaty HM. Epidemiology of Helicobacter pylori infection. Best Pract Res Clin Gastroenterol 2007;21:205-14. 10.1016/j.bpg.2006.10.00517382273
3
Youn HS, Baik SC, Cho YK, Woo HO, Ahn YO, Kim K, et al. Comparison of Helicobacter pylori infection between Fukuoka, Japan and Chinju, Korea. Helicobacter 1998;3:9-14. 10.1046/j.1523-5378.1998.08011.x9546112
4
Shin A, Kim J, Park S. Gastric cancer epidemiology in Korea. J Gastric Cancer 2011;11:135-40. 10.5230/jgc.2011.11.3.13522076217PMC3204471
5
Kim N, Park RY, Cho SI, Lim SH, Lee KH, Lee W, et al. Helicobacter pylori infection and development of gastric cancer in Korea: long-term follow-up. J Clin Gastroenterol 2008;42:448-54. 10.1097/MCG.0b013e318046eac318344895
6
Ko JS, Kim KM, Oh YL, Seo JK. cagA, vacA, and iceA genotypes of Helicobacter pylori in Korean children. Pediatr Int 2008;50:628-31.
7
Yamaoka Y. Mechanisms of disease: Helicobacter pylori virulence factors. Nat Rev Gastro Hepatol 2010;7:629-41. 10.1038/nrgastro.2010.15420938460PMC3137895
8
Kalali B, Mejías Luque R, Javaheri A, Gerhard M. H. pylori virulence factors: influence on immune system and pathology. Mediators Inflamm 2014;2014:426309. 10.1155/2014/42630924587595PMC3918698
9
Shiota S, Suzuki R, Yamaoka Y. The significance of virulence factors in Helicobacter pylori. J Dig Dis 2013;14:341-9. 10.1111/1751-2980.1205423452293PMC3721066
10
Axon A. Helicobacter pylori and public health. Helicobacter 2014;19 Suppl 1:68-73. 10.1111/hel.1215525167948
11
Kalali B, Mejías Luque R, Javaheri A, Gerhard M. H. pylori virulence factors: influence on immune system and pathology. Mediators Inflamm 2014;2014:426309. 10.1155/2014/42630924587595PMC3918698
12
Ando T, Wassenaar TM, Peek Jr RM, Aras RA, Tschumi AI, van Doorn LJ, et al. A Helicobacter pylori restriction endonuclease-replacing gene, hrgA, is associated with gastric cancer in Asian strains. Cancer Res 2002;62:2385-9.
13
Choe YH, Kim PS, Lee DH, Kim HK, Kim YS, Shin YW, et al. Diverse vacA allelic types of Helicobacter pylori in Korea and clinical correlation. Yonsei Med J 2002;43:351-6. 10.3349/ymj.2002.43.3.35112089744
14
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893-917. 10.1002/ijc.2551621351269
15
Fock KM, Ang TL. Epidemiology of Helicobacter pylori infection and gastric cancer in Asia. J Gastroenterol Hepatol 2010;25:479-86. 10.1111/j.1440-1746.2009.06188.x20370726
16
Kao CY, Sheu BS, Wu JJ. Helicobacter pylori infection: An overview of bacterial virulence factors and pathogenesis. Biomed J 2016;39:14-23. 10.1016/j.bj.2015.06.00227105595PMC6138426
17
Skene C, Young A, Every A, Sutton P. Helicobacter pylori flagella: antigenic profile and protective immunity. FEMS Immunol Med Microbiol 2007;50:249-56. 10.1111/j.1574-695X.2007.00263.x17521391
18
Miller EF, Maier RJ. Ammonium metabolism enzymes aid Helicobacter pylori acid resistance. J Bacteriol 2014;196:3074-81. 10.1128/JB.01423-1324936052PMC4135655
19
Schwartz JT, Allen LAH. Role of urease in megasome formation and Helicobacter pylori survival in macrophages. J Leukoc Biol 2006;79:1214-25. 10.1189/jlb.010603016543403PMC1868427
20
Loh JT, Shum MV, Jossart SD, Campbell AM, Sawhney N, McDonald WH, et al. Delineation of the pH-responsive regulon controlled by the Helicobacter pylori ArsRS two-component system. Infect Immun 2021;89:e00597-20. 10.1128/IAI.00597-2033526561PMC8090972
21
Yamaoka Y, Ojo O, Fujimoto S, Odenbreit S, Haas R, Gutierrez O, et al. Helicobacter pylori outer membrane proteins and gastroduodenal disease. Gut 2006;55:775-81. 10.1136/gut.2005.08301416322107PMC1856239
22
Ansari S, Yamaoka Y. Helicobacter pylori BabA in adaptation for gastric colonization. World J Gastroenterol 2017;23:4158-69. 10.3748/wjg.v23.i23.415828694656PMC5483490
23
McGowan CC, Necheva AS, Forsyth MH, Cover TL, Blaser MJ. Promoter analysis of Helicobacter pylori genes with enhanced expression at low pH. Mol Microbiol 2003;48:1225-39. 10.1046/j.1365-2958.2003.03500.x12787351
24
O'Riordan AA, Morales VA, Mulligan L, Faheem N, Windle HJ, Kelleher DP. Alkyl hydroperoxide reductase: a candidate Helicobacter pylori vaccine. Vaccine 2012;30:3876-84. 10.1016/j.vaccine.2012.04.00222512976
25
Baj J, Forma A, Sitarz M, Portincasa P, Garruti G, Krasowska D, et al. Helicobacter pylori virulence factors-mechanisms of bacterial pathogenicity in the gastric microenvironment. Cells 2020;10:27. 10.3390/cells1001002733375694PMC7824444
26
González-López MA, Velázquez-Guadarrama N, Romero-Espejel ME, de Jesús Olivares-Trejo J. Helicobacter pylori secretes the chaperonin GroEL (HSP60), which binds iron. FEBS Lett 2013;587:1823-8. 10.1016/j.febslet.2013.04.04823684642
27
Fujimoto S, Ojo OO, Arnqvist A, Wu JY, Odenbreit S, Haas R, et al. Helicobacter pylori BabA expression, gastric mucosal injury, and clinical outcome. Clin Gastroenterol Hepatol 2007;5:49-58. 10.1016/j.cgh.2006.09.01517157077PMC3118416
28
Kennemann L, Brenneke B, Andres S, Engstrand L, Meyer TF, Aebischer T, et al. In vivo sequence variation in HopZ, a phase-variable outer membrane protein of Helicobacter pylori. Infect Immun 2012;80:4364-73. 10.1128/IAI.00977-1223027539PMC3497411
29
Raghwan, Chowdhury R. Host cell contact induces Fur‐dependent expression of virulence factors cagA and vacA in Helicobacter pylori. Helicobacter 2014;19:17-25. 10.1111/hel.1208724020886
30
Kawahara Y, Hirashita Y, Tamura C, Kudo Y, Sakai K, Togo K, et al. Helicobacter pylori infection modulates endogenous hydrogen sulfide production in gastric cancer AGS cells. Helicobacter 2020;25:e12732. 10.1111/hel.1273232713122
31
Seo JH, Lim JW, Kim H, Kim KH. Helicobacter pylori in a Korean isolate activates mitogen-activated protein kinases, AP-1, and NF-κB and induces chemokine expression in gastric epithelial AGS cells. Lab Invest 2004;84:49-62. 10.1038/labinvest.370001014631383
32
Backert S, Gressmann H, Kwok T, Zimny Arndt U, König W, Jungblut PR, et al. Gene expression and protein profiling of AGS gastric epithelial cells upon infection with Helicobacter pylori. Proteomics 2005;5:3902-18. 10.1002/pmic.20040124016145711
33
Kim N, Marcus EA, Wen Y, Weeks DL, Scott DR, Jung HC, et al. Genes of Helicobacter pylori regulated by attachment to AGS cells. Infect Immun 2004;72:2358-68. 10.1128/IAI.72.4.2358-2368.200415039361PMC375207
34
Joo JS, Park KC, Song JY, Kim DH, Lee KJ, Kwon YC, et al. A thin‐layer liquid culture technique for the growth of Helicobacter pylori. Helicobacter 2010;15:295-302. 10.1111/j.1523-5378.2010.00767.x20633190
35
Antiabong JF, Ngoepe MG, Abechi AS. Semi-quantitative digital analysis of polymerase chain reaction-electrophoresis gel: Potential applications in low-income veterinary laboratories. Vet World 2016;9:935-9. 10.14202/vetworld.2016.935-93927733792PMC5057030
36
Sukri A, Hanafiah A, Kosai NR, Mohammed Taher M, Mohamed R. New insight on the role of Helicobacter pylori cagA in the expression of cell surface antigens with important biological functions in gastric carcinogenesis. Helicobacter 2022;27:e12913. 10.1111/hel.1291335848223
37
Loh JT, Torres VJ, Cover TL. Regulation of Helicobacter pylori cagA expression in response to salt. Cancer Res 2007;67:4709-15. 10.1158/0008-5472.CAN-06-474617510398
38
Yamaoka Y, Graham DY. Helicobacter pylori virulence and cancer pathogenesis. Future Oncol 2014;10:1487-500. 10.2217/fon.14.2925052757PMC4197059
39
Karita M, Tummuru MK, Wirth HP, Blaser MJ. Effect of growth phase and acid shock on Helicobacter pylori cagA expression. Infect Immun 1996;64:4501-7. 10.1128/iai.64.11.4501-4507.19968890198PMC174404
40
Merrell DS, Goodrich ML, Otto G, Tompkins LS, Falkow S. pH-regulated gene expression of the gastric pathogen Helicobacter pylori. Infect Immun 2003;71:3529-39. 10.1128/IAI.71.6.3529-3539.200312761138PMC155744
41
Ernst FD, Bereswill S, Waidner B, Stoof J, Mäder U, Kusters JG, et al. Transcriptional profiling of Helicobacter pylori Fur-and iron-regulated gene expression. Microbiology 2005;151:533-46. 10.1099/mic.0.27404-015699202
42
Foegeding NJ, Caston RR, McClain MS, Ohi MD, Cover TL. An overview of Helicobacter pylori VacA toxin biology. Toxins (Basel). 2016;8:173. 10.3390/toxins806017327271669PMC4926140
43
Mendoza JA, Ignacio JL, Buckley CM. The Hsp60 protein of Helicobacter pylori exhibits chaperone and ATPase activities at elevated temperatures. BioChem 2021;1:19-25. 10.3390/biochem1010002
44
Blase JL, Campbell PT, Gapstur SM, Pawlita M, Michel A, Waterboer T, et al. Prediagnostic Helicobacter pylori antibodies and colorectal cancer risk in an elderly, caucasian population. Helicobacter 2016;21:488-92. 10.1111/hel.1230527006167
45
El Hafa F, Wang T, Ndifor VM, Jin G. Association between Helicobacter pylori antibodies determined by multiplex serology and gastric cancer risk: A meta‐analysis. Helicobacter 2022;27:e12881. 10.1111/hel.1288135212073
46
Jala I, Almanfaluthi ML, Laha T, Kanthawong S, Tangkawattana S, Saichua P, et al. Helicobacter pylori GroEL seropositivity is associated with an increased risk of Opisthorchis viverrini-associated hepatobiliary abnormalities and cholangiocarcinoma. Korean J Parasitol 2021;59:363-8. 10.3347/kjp.2021.59.4.36334470087PMC8413853
47
Yamaguchi H, Osaki T, Taguchi H, Hanawa T, Yamamoto T, Kamiya S. Relationship between expression of HSP60, urease activity, production of vacuolating toxin, and adherence activity of Helicobacter pylori. J Gastroenterol 1998;33:6-9.
48
Reyes VE, Peniche AG. Helicobacter pylori deregulates T and B cell signaling to trigger immune evasion. Curr Top Microbiol Immunol 2019;421:229-65. 10.1007/978-3-030-15138-6_1031123892PMC7050993
49
Šterbenc A, Jarc E, Poljak M, Homan M. Helicobacter pylori virulence genes. World J Gastroenterol 2019;25:4870-84. 10.3748/wjg.v25.i33.487031543679PMC6737321
50
De la Cruz MA, Ares MA, Von Bargen K, Panunzi LG, Martínez-Cruz J, Valdez Salazar HA, et al. Gene expression profiling of transcription factors of Helicobacter pylori under different environmental conditions. Front Microbiol 2017;8:615. 10.3389/fmicb.2017.00615
51
Akada JK, Shirai M, Takeuchi H, Tsuda M, Nakazawa T. Identification of the urease operon in Helicobacter pylori and its control by mRNA decay in response to pH. Mol Microbiol 2000;36:1071-84. 10.1046/j.1365-2958.2000.01918.x10844692
52
Dossumbekova A, Prinz C, Mages J, Lang R, Kusters JG, Van Vliet AH, et al. Helicobacter pylori HopH (OipA) and bacterial pathogenicity: genetic and functional genomic analysis of hopH gene polymorphisms. J Infect Dis 2006;194:1346-55. 10.1086/50842617054063
53
Marcus EA, Sachs G, Scott DR. Acid‐regulated gene expression of Helicobacter pylori: insight into acid protection and gastric colonization. Helicobacter 2018;23:e12490. 10.1111/hel.1249029696729PMC5980792
54
Styer CM, Hansen LM, Cooke CL, Gundersen AM, Choi SS, Berg DE, et al. Expression of the BabA adhesin during experimental infection with Helicobacter pylori. Infect Immun 2010;78:1593-600. 10.1128/IAI.01297-0920123715PMC2849406
55
Kable ME, Hansen LM, Styer CM, Deck SL, Rakhimova O, Shevtsova A, et al. Host determinants of expression of the Helicobacter pylori BabA adhesin. Sci Rep 2017;7:46499. 10.1038/srep4649928418004PMC5394467
56
Lee DH, Ha JH, Shin JI, Kim KM, Choi Jg, Park S, et al. Increased risk of severe gastric symptoms by virulence factors vacAs1c, alpA, babA2, and hopZ in Helicobacter pylori infection. J Microbiol Biotechnol 2021;31:368-79. 10.4014/jmb.2101.0102333622995PMC9705970
Information
  • Publisher :The Korean Society for Microbiology
  • Publisher(Ko) :대한미생물학회
  • Journal Title :JOURNAL OF BACTERIOLOGY AND VIROLOGY
  • Volume : 52
  • No :4
  • Pages :160-169
  • Received Date : 2022-11-30
  • Revised Date : 2022-12-07
  • Accepted Date : 2022-12-08
  • DOI :https://doi.org/10.4167/jbv.2022.52.4.160
Journal Informaiton JOURNAL OF BACTERIOLOGY AND VIROLOGY JOURNAL OF BACTERIOLOGY AND VIROLOGY
  • NRF
  • 임플란트학회 전용 배너
  • KOFST
  • crossref crossmark
  • crossref cited-by
  • crossref funder-registry
  • crosscheck
  • orcid
  • open access
  • ccl
Journal Informaiton Journal Informaiton - close