1887

Abstract

Purpose. Multiple Helicobacter pylori strains colonize and coexist in the stomach of one single patient, carrying heterogeneous distributions of cag genotypes. The oesophagus provides a niche for H. pylori colonization; however, little is known about its adaptive role.

Methodology. Using PCR for cagA, cagE and virB11 genes from cag-pathogenicity island (PAI) and Etest for antimicrobial susceptibility test, we determined cag-PAI genotypes associated with H. pylori virulence, when positive cultures were matching in both the stomach and the oesophagus (96 isolates; 8 out of 80 dyspeptic patients).

Results. The stomach showed complete cag-PAI islands in 77 % of the isolates, whereas the oesophagus showed complete cag-PAI islands only in 44 % of the isolates. Expression of CagA and interleukin 8 correlated with inflammatory processes and histopathological changes in the stomach, but not in the oesophagus. Different cag-PAI profiles were found in both mucosae of an individual host, and at least one oesophagus profile corresponded to one profile identified in stomach. The antibiotic resistance profiles showed variability in the colonization by single or mixed H. pylori isolates in the gastric and oesophageal mucosa both intra- and inter-individuals.

Conclusion. These results demonstrate colonization with multiple H. pylori isolates in the oesophageal mucosa, like those found in the stomach of individual hosts. H. pylori was characterized by a dominant partial island, low interleukin 8 induction with lower histopathological damage and lower antibiotic resistance, suggesting that the microenvironmental changes in individual hosts select less virulent isolates in the oesophagus than in the stomach. New approaches to ensure effective eradication therapy in multi-resistant H. pylori strains must be developed.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.000409
2017-02-21
2019-10-16
Loading full text...

Full text loading...

/deliver/fulltext/jmm/66/2/226.html?itemId=/content/journal/jmm/10.1099/jmm.0.000409&mimeType=html&fmt=ahah

References

  1. Atherton JC, Blaser MJ. Coadaptation of Helicobacter pylori and humans: ancient history, modern implications. J Clin Invest 2009;119:2475–2487 [CrossRef][PubMed]
    [Google Scholar]
  2. Argent RH, Hale JL, El-Omar EM, Atherton JC. Differences in Helicobacter pylori CagA tyrosine phosphorylation motif patterns between western and East Asian strains, and influences on interleukin-8 secretion. J Med Microbiol 2008;57:1062–1067 [CrossRef][PubMed]
    [Google Scholar]
  3. Hatakeyama M. Helicobacter pylori CagA and gastric cancer: a paradigm for hit-and-run carcinogenesis. Cell Host Microbe 2014;15:306–316 [CrossRef][PubMed]
    [Google Scholar]
  4. Sozzi M, Tomasini ML, Vindigni C, Zanussi S, Tedeschi R et al. Heterogeneity of cag genotypes and clinical outcome of Helicobacter pylori infection. J Lab Clin Med 2005;146:262–270 [CrossRef][PubMed]
    [Google Scholar]
  5. Lima VP, de Lima MA, Ferreira MV, Barros MA, Rabenhorst SH. The relationship between Helicobacter pylori genes cagE and virB11 and gastric cancer. Int J Infect Dis 2010;14:e613e617 [CrossRef][PubMed]
    [Google Scholar]
  6. Kraft C, Suerbaum S. Mutation and recombination in Helicobacter pylori: mechanisms and role in generating strain diversity. Int J Med Microbiol 2005;295:299–305 [CrossRef][PubMed]
    [Google Scholar]
  7. Chiurillo MA, Moran Y, Cañas M, Valderrama E, Granda N et al. Genotyping of Helicobacter pylori virulence-associated genes shows high diversity of strains infecting patients in western Venezuela. Inter J Infect Dis 2013;17:e750e756 [CrossRef]
    [Google Scholar]
  8. Malfertheiner P, Megraud F, O'Morain CA, Atherton J, Axon AT et al. Management of Helicobacter pylori infection—the Maastricht IV/ Florence Consensus Report. Gut 2012;61:646–664 [CrossRef][PubMed]
    [Google Scholar]
  9. Patra R, Chattopadhyay S, de R, Ghosh P, Ganguly M et al. Multiple infection and microdiversity among Helicobacter pylori isolates in a single host in India. PLoS One 2012;7:e43370 [CrossRef][PubMed]
    [Google Scholar]
  10. Antonio-Rincón F, López-Vidal Y, Castillo-Rojas G, Lazcano-Ponce EC, Ponce-de-León S et al. Pathogenicity island cag, vacA and IS605 genotypes in Mexican strains of Helicobacter pylori associated with peptic ulcers. Ann Clin Microbiol Antimicrob 2011;10:18 [CrossRef][PubMed]
    [Google Scholar]
  11. Ashour AA, Magalhães PP, Mendes EN, Collares GB, de Gusmão VR et al. Distribution of vacA genotypes in Helicobacter pylori strains isolated from Brazilian adult patients with gastritis, duodenal ulcer or gastric carcinoma. FEMS Immunol Med Microbiol 2002;33:173–178 [CrossRef][PubMed]
    [Google Scholar]
  12. Ren L, Liao YL, Song Y, Guo Y, Mao XH et al. High frequency variations of Helicobacter pylori isolates in individual hosts in a Chinese population. Int J Infect Dis 2012;16:e358e363 [CrossRef][PubMed]
    [Google Scholar]
  13. Ghose C, Perez-Perez GI, van Doorn LJ, Domínguez-Bello MG, Blaser MJ. High frequency of gastric colonization with multiple Helicobacter pylori strains in Venezuelan subjects. J Clin Microbiol 2005;43:2635–2641 [CrossRef][PubMed]
    [Google Scholar]
  14. Cellini L, Grande R, Artese L, Marzio L. Detection of Helicobacter pylori in saliva and oesophagus. New Microbiol 2010;37:351–357
    [Google Scholar]
  15. Contreras M, Salazar V, García-Amado MA, Reyes N, Aparcero M et al. High frequency of Helicobacter pylori in the esophageal mucosa of dyspeptic patients and its possible association with histopathological alterations. Int J Infect Dis 2012;16:e364e370 [CrossRef][PubMed]
    [Google Scholar]
  16. Weiss J, Tsang TK, Meng X, Zhang H, Kilner E et al. Detection of Helicobacter pylori gastritis by PCR: correlation with inflammation scores and immunohistochemical and CLOtest findings. Am J Clin Pathol 2008;129:89–96 [CrossRef][PubMed]
    [Google Scholar]
  17. Pei Z, Yang L, Peek RM, Levine SM Jr, Pride DT et al. Bacterial biota in reflux esophagitis and Barrett's esophagus. World J Gastroenterol 2005;11:7277–7283 [CrossRef][PubMed]
    [Google Scholar]
  18. Kariya S, Okano M, Nishizaki K. An association between Helicobacter pylori and upper respiratory tract disease: fact or fiction?. World J Gastroenterol 2014;20:1470–1484 [CrossRef][PubMed]
    [Google Scholar]
  19. Contreras M, Abrante L, Salazar V, Reyes N, García-Amado MA et al. Heterogeneity of cag genotypes of Helicobacter pylori in the esophageal mucosa of dyspeptic patients and its relation to histopathological outcomes. Int J Infect Dis 2014;26:91–95 [CrossRef][PubMed]
    [Google Scholar]
  20. Domínguez-Bello MG, Michelangeli F, Romero R, Beker B, Lara D et al. Modification of Christensen urease test as an inexpensive tool for detection of Helicobacter pylori. Diagn Microbiol Infect Dis 1997;28:149–152 [CrossRef][PubMed]
    [Google Scholar]
  21. Clinical Laboratory Standards Institute (CLSI) Methods for antimicrobial dilution and disk susceptibility testing of infrequently isolated or fastidious bacteria approved guideline, 2nd ed. CLSI document M45-A2 Wayne, PA: Clinical and Laboratory Standards Institute; 2010
    [Google Scholar]
  22. Seck A, Burucoa C, Dia D, Mbengue M, Onambele M et al. Primary antibiotic resistance and associated mechanisms in Helicobacter pylori isolates from Senegalese patients. Ann Clin Microbiol Antimicrob 2013;12:3 [CrossRef][PubMed]
    [Google Scholar]
  23. Germani Y, Dauga C, Duval P, Huerre M, Levy M et al. Strategy for the detection of Helicobacter species by amplification of 16S rRNA genes and identification of H. felis in a human gastric biopsy. Res Microbiol 1997;148:315–326 [CrossRef][PubMed]
    [Google Scholar]
  24. Kansau I, Raymond J, Bingen E, Courcoux P, Kalach N et al. Genotyping of Helicobacter pylori isolates by sequencing of PCR products and comparison with the RAPD technique. Res Microbiol 1996;147:661–669 [CrossRef][PubMed]
    [Google Scholar]
  25. Peek RM Jr, Miller GG, Tham KT, Pérez-Pérez GI, Cover TL et al. Detection of Helicobacter pylori gene expression in human gastric mucosa. J Clin Microbiol 1995;33:28–32[PubMed]
    [Google Scholar]
  26. Tomb JF, White O, Kerlavage AR, Clayton RA, Sutton GG et al. The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature 1997;388:539–547 [CrossRef][PubMed]
    [Google Scholar]
  27. Rugge M, Busatto G, Cassaro M, Shiao YH, Russo V et al. Patients younger than 40 years with gastric carcinoma: Helicobacter pylori genotype and associated gastritis phenotype. Cancer 1999;85:2506–2511[PubMed][CrossRef]
    [Google Scholar]
  28. Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis. the updated Sydney system. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol 1996;20:1161–1181[PubMed][CrossRef]
    [Google Scholar]
  29. Soltermann A, Koetzer S, Eigenmann F, Komminoth P. Correlation of Helicobacter pylori virulence genotypes vacA and cagA with histological parameters of gastritis and patient's age. Mod Pathol 2007;20:878–883 [CrossRef][PubMed]
    [Google Scholar]
  30. Guenther T, Hackelsberger A, Kuester D, Malfertheiner P, Roessner A. Reflux esophagitis or Helicobacter infection? - Diagnostic value of the inflammatory pattern in metaplastic mucosa at the squamocolumnar junction. Pathol Res Pract 2007;203:831–837 [CrossRef][PubMed]
    [Google Scholar]
  31. Brkić DV, Katičić M, Bedenić B, Stanko AP, Plečko V. Detection of virulence gene belonging to cag pathogenicity island in Helicobacter pylori isolates after multiple unsuccessful eradication therapy in Northwest Croatia. Period Biol 2016;118:45–52[CrossRef]
    [Google Scholar]
  32. Chiurillo MA, Moran YH, Cañas M, Valderrama EJ, Armanie E. Infection with specific Helicobacter pylori-cag pathogenicity island strains is associated with interleukin-1B gene polymorphisms in Venezuelan chronic gastritis patients. Dig Dis Sci 2011;56:449–456 [CrossRef][PubMed]
    [Google Scholar]
  33. Matteo MJ, Granados G, Pérez CV, Olmos M, Sanchez C et al. Helicobacter pylori cag pathogenicity island genotype diversity within the gastric niche of a single host. J Med Microbiol 2007;56:664–669 [CrossRef][PubMed]
    [Google Scholar]
  34. Boyanova L, Yordanov D, Gergova G, Markovska R, Mitov I. Benefits of Helicobacter pylori cagE genotyping in addition to cagA genotyping: a Bulgarian study. Antonie van Leeuwenhoek 2011;100:529–535 [CrossRef][PubMed]
    [Google Scholar]
  35. Patra R, Chattopadhyay S, de R, Datta S, Chowdhury A et al. Intact cag pathogenicity island of Helicobacter pylori without disease association in Kolkata, India. Int J Med Microbiol 2011;301:293–302 [CrossRef][PubMed]
    [Google Scholar]
  36. Martínez JD, Henao SC, Lizarazo JI. Antibiotic resistance of Helicobacter pylori in Latin America and the Caribbean. Rev Col Gastroenterol 2014;29:217–226
    [Google Scholar]
  37. Urrestarazu M, Serrano N, Piñero R, Cavazza M. Susceptibilidad de Helicobacter pylori a los antimicrobianos/Antimicrobial susceptibility of Helicobacter pylori. Rev Soc Venez Microbiol 2003;23:14–15
    [Google Scholar]
  38. Picoli SU, Mazzoleni LE, Fernández H, de Bona LR, Neuhauss E et al. Resistance to amoxicillin, clarithromycin and ciprofloxacin of Helicobacter pylori isolated from Southern Brazil patients. Rev Inst Med Trop Sao Paulo 2014;56:197–200 [CrossRef][PubMed]
    [Google Scholar]
  39. Fasciana T, Calà C, Bonura C, di Carlo E, Matranga D et al. Resistance to clarithromycin and genotypes in Helicobacter pylori strains isolated in Sicily. J Med Microbiol 2015;64:1408–1414 [CrossRef][PubMed]
    [Google Scholar]
  40. Fathi MS, El-Folly RF, Hassan RA, El-Arab ME. Genotypic and phenotypic patterns of antimicrobial susceptibility of Helicobacter pylori strains among Egyptian patients. EJMHG 2013;14:235–246 [CrossRef]
    [Google Scholar]
  41. Hung KH, Sheu BS, Chang WL, Wu HM, Liu CC et al. Prevalence of primary fluoroquinolone resistance among clinical isolates of Helicobacter pylori at a university hospital in Southern Taiwan. Helicobacter 2009;14:61–65 [CrossRef][PubMed]
    [Google Scholar]
  42. Raymond J, Lamarque D, Kalach N, Chaussade S, Burucoa C. High level of antimicrobial resistance in French Helicobacter pylori isolates. Helicobacter 2010;15:21–27 [CrossRef][PubMed]
    [Google Scholar]
  43. Talebi Bezmin Abadi A, Ghasemzadeh A, Taghvaei T, Mobarez AM. Primary resistance of Helicobacter pylori to levofloxacin and moxifloxacine in Iran. Intern Emerg Med 2012;7:447–452 [CrossRef][PubMed]
    [Google Scholar]
  44. Tay CY, Windsor HM, Thirriot F, Lu W, Conway C et al. Helicobacter pylori eradication in Western Australia using novel quadruple therapy combinations. Aliment Pharmacol Ther 2012;36:1076–1083 [CrossRef][PubMed]
    [Google Scholar]
  45. Teh X, Khosravi Y, Lee WC, Leow AH, Loke MF et al. Functional and molecular surveillance of Helicobacter pylori antibiotic resistance in Kuala Lumpur. PLoS One 2014;9:e101481 [CrossRef][PubMed]
    [Google Scholar]
  46. Wang LH, Cheng H, Hu FL, Li J. Distribution of gyrA mutations in fluoroquinolone-resistant Helicobacter pylori strains. World J Gastroenterol 2010;16:2272–2277 [CrossRef][PubMed]
    [Google Scholar]
  47. Chung JW, Lee GH, Jeong JY, Lee SM, Jung JH et al. Resistance of Helicobacter pylori strains to antibiotics in Korea with a focus on fluoroquinolone resistance. J Gastroenterol Hepatol 2012;27:493–497 [CrossRef][PubMed]
    [Google Scholar]
  48. Liu ZQ, Zheng PY, Yang PC. Efflux pump gene hefA of Helicobacter pylori plays an important role in multidrug resistance. World J Gastroenterol 2008;14:5217–5222 [CrossRef][PubMed]
    [Google Scholar]
  49. Mégraud F. H. pylori antibiotic resistance: prevalence, importance, and advances in testing. Gut 2004;53:1374–1384 [CrossRef][PubMed]
    [Google Scholar]
  50. de Francesco V, Giorgio F, Hassan C, Manes G, Vannella L et al. Worldwide H. pylori antibiotic resistance: a systematic review. J Gastrointestin Liver Dis 2010;19:409–414[PubMed]
    [Google Scholar]
  51. Mégraud F, Lehours P. Helicobacter pylori detection and antimicrobial susceptibility testing. Clin Microbiol Rev 2007;20:280–322 [CrossRef][PubMed]
    [Google Scholar]
  52. Saracino IM, Zullo A, Holton J, Castelli V, Fiorini G et al. High prevalence of primary antibiotic resistance in Helicobacter pylori isolates in Italy. J Gastrointestin Liver Dis 2012;21:363–365[PubMed]
    [Google Scholar]
  53. Chu YT, Wang YH, Wu JJ, Lei HY. Invasion and multiplication of Helicobacter pylori in gastric epithelial cells and implications for antibiotic resistance. Infect Immun 2010;78:4157–4165 [CrossRef][PubMed]
    [Google Scholar]
  54. Peterson WL. The role of antisecretory drugs in the treatment of Helicobacter pylori infection. Aliment Pharmacol Ther 1997;11:21–25 [CrossRef][PubMed]
    [Google Scholar]
  55. Sharma SA, Tummuru MK, Miller GG, Blaser MJ. Interleukin-8 response of gastric epithelial cell lines to Helicobacter pylori stimulation in vitro. Infect Immun 1995;63:1681–1687[PubMed]
    [Google Scholar]
  56. Ying GX, Wen Sheng LI, Xia ZL, Tao WH. CagA+ H. pylori filtrate induces cytokine IL-8 secretion by esophageal squamous carcinoma EC 109 cells via a p38 pathway. Indian J Pathol Microbiol 2014;57:13–18 [CrossRef][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.000409
Loading
/content/journal/jmm/10.1099/jmm.0.000409
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error