Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Gut Pathogens
Published in: Gut Pathogens 1/2016

Open Access 01-12-2016 | Research

Helicobacter pylori strains harboring babA2 from Indian sub population are associated with increased virulence in ex vivo study

Authors: Prachetash Ghosh, Avijit Sarkar, Mou Ganguly, Raghwan, Jawed Alam, Ronita De, Asish K. Mukhopadhyay

Published in: Gut Pathogens | Issue 1/2016

Login to get access

Abstract

Background

The babA2 gene along with the cagA and vacA of Helicobacter pylori has been considered as a risk factor for the disease outcome in certain populations. This study was aimed to understand the role of babA2 of H. pylori with the background of cagA and vacA in disease manifestations in Indian sub population.

Methods

A total of 114 H. pylori strains isolated from duodenal ulcer (DU) (n = 53) and non-ulcer dyspepsia (NUD) patients (n = 61) were screened for the prevalence of these virulence markers by PCR. The comparative study of IL-8 production and apoptosis were done by co-culturing the AGS cell line with H. pylori strains with different genotypes. Adherence assay was performed with babA2 positive and negative strains. Two isogenic mutants of babA2 were constructed and the aforesaid comparative studies were carried out.

Results

PCR results indicated that 90.6 % (48/53), 82 % (50/61) and 73.6 % (39/53) strains from DU patients were positive for cagA, vacA, and babA2, respectively. Whereas the prevalence of these genes in NUD subjects were 70.5 % (43/61); 69.8 % (37/53), and 65.6 % (39/61), respectively. Although adherence to AGS cells was comparable among strains with babA2 positive and negative genotypes, but the triple positive strains could induce highest degree of IL-8 production and apoptosis, followed by the cagA −/vacA −/babA2 + strains and triple negative strains, respectively. The wild type strains showed significantly higher IL-8 induction as well as apoptosis in ex vivo than its isogenic mutant of babA2.

Conclusion

PCR study demonstrated that there was no significant association between the distribution of babA2 genotype or of triple positive strains and disease outcome in this sub population. The adherence assay showed that there was no significant difference in the extent of adherence to AGS cells among babA2 positive and negative strains. But the ex vivo study indicated that the triple positive or even the babA2 only positive strains are involved in increased virulence. The wild type strains also exhibited increased virulence compared to the babA2 mutant strains. This inconsistency demonstrated that bacterial genotype along with host genetic polymorphisms or other factors play important role in determining the clinical manifestation of H. pylori infections.
Literature
1.
Brown LM. Helicobacter pylori: epidemiology and routes of transmission. Epidemiol Rev. 2002;22:283–97.CrossRef
2.
Covacci A, Telford JL, Giudice GD, Parsonnet J, Rappuoli R. Helicobacter pylori virulence and genetic geography. Science. 1999;284:1328–33.PubMedCrossRef
3.
Graham DY, Adam E, Reddy GT, Agarwal JP, Agarwal R, Evans DJ, Malaty HM, Evans DG. Seroepidemiology of Helicobacter pylori infection in India. Comparison of developing and developed countries. Dig Dis Sci. 1991;36:1084–8.PubMedCrossRef
4.
Singh V, Trikha B, Nain CK, Singh K, Vaiphei K. Epidemiology of Helicobacter pylori and peptic ulcer in India. J Gastroenterol Hepatol. 2002;17:659–65.PubMedCrossRef
5.
Alam J, Maiti S, Ghosh P, De R, Chowdhury A, Das S, Macaden R, Devarbhavi H, Ramamurthy T, Mukhopadhyay AK. Significant association of the dupA gene of Helicobacter pylori with duodenal ulcer development in a South-east Indian population. J Med Microbiol. 2012;61:1295–302. doi:10.​1099/​jmm.​0.​038398-0.PubMedCrossRef
6.
Suerbaum S, Michetti P. Helicobacter pylori infection. N Eng J Med. 2002;347:1157–86.CrossRef
7.
Censini S, Lange C, Xiang Z, Crabtree JE, Ghiara P, Borodovsky M, Rappuoli R, Covacci A. Cag pathogenicity island of Helicobacter pylori, encodes type I-specific and diseases associated virulence factors. Proc Natl Acad Sci. 1996;93:14648–53.PubMedPubMedCentralCrossRef
8.
Broutet N, Marais A, Lamouliatte H, de Mascarel A, Samoyeau R, Salamon R, Megraud F. cagA status and eradication treatment outcome of anti-Helicobacter pylori triple therapies in patients with nonulcer dyspepsia. J Clin Microbiol. 2001;39:1319–22.PubMedPubMedCentralCrossRef
9.
Rahman M, Mukhopadhyay AK, Nahar S, et al. DNA-level characterization of Helicobacter pylori strains from patients with overt disease and with benign infections in Bangladesh. J Clin Microbiol. 2003;41:2008–14.PubMedPubMedCentralCrossRef
10.
11.
Chattopadhyay S, Patra R, Chatterjee R, De R, Alam J, Ramamurthy T, Chowdhury A, Nair GB, Berg DE, Mukhopadhyay AK. Distinct repeat motifs at the C-terminal region of CagA of Helicobacter pylori strains isolated from diseased patients and asymptomatic individuals in West Bengal, India. Gut Pathog. 2012;4:4. doi:10.​1186/​1757-4749-4-4.PubMedPubMedCentralCrossRef
12.
Montecucco C, Papini E, de Bernard M, Telford JL, Rappuoli R. Helicobacter pylori vacuolating cytotoxin and associated pathogenic factors. In: Alouf JE, Freer JH, editors. The comparative source book of bacterial protein toxins. San Diego: Academic Press; 1999. p. 264–83.
13.
Chattopadhyay S, Datta S, Chowdhury A, Chowdhury S, Mukhopadhyay AK, Rajendran K, Bhattacharya SK, Berg DE, Nair GB. Virulence genes in Helicobacter pylori strains from West Bengal residents with overt H. pylori-associated disease and healthy volunteers. J Clin Microbiol. 2002;40:2622–5.PubMedPubMedCentralCrossRef
14.
15.
Ilver D, Arnqvist A, Ogren J, Frick IM, Kersulyte D, Incecik ET, Berg DE, Covacci A, Engstrand L, Boren T. Helicobacter pylori adhesin binding fucosylated histo-blood group antigens revealed by retagging. Science. 1998;279:373–7.PubMedCrossRef
16.
17.
Rad R, Gerhard M, Lang R, Schöniger M, Rösch T, Schepp W, Becker I, Wagner H, Prinz C. The Helicobacter pylori blood group antigen-binding adhesin facilitates bacterial colonization and augments a nonspecific immune response. J Immunol. 2002;168:3033–41.PubMedCrossRef
18.
Boren T, Falk P, Roth KA, Larson G, Normark S. Attachment of Helicobacter pylori to human gastric epithelium mediated by blood group antigens. Science. 1993;262:1892–5.PubMedCrossRef
19.
Megraud F, Trimoulet pascale, Lamouliatte H, Boyanova L. Bactericidal effect of amoxicillin on Helicobacter pylori in an in vitro model using epithelial cells. Antimicrob Agents Chemother. 1991;35:869–72.
20.
Gerhard M, Lehn N, Neumayer N, Boren T, Rad R, Schepp W, Miehlke S, Classen M, Prinz C. Clinical relevance of the Helicobacter pylori gene for blood-group antigen-binding adhesion. Proc Natl Acad Sci. 1999;96:12778–83.PubMedPubMedCentralCrossRef
21.
Oliveira AG, Santos A, Guerra JB, et al. babA2-and cagA-positive Helicobacter pylori strains are associated with duodenal ulcer and gastric carcinoma in Brazil. J Clin Microbiol. 2003;41:3964–6.PubMedPubMedCentralCrossRef
22.
Mattar R, dos Santos AF, Eisig JN, Rodrigues TN, Silva FM, Lupinacci RM, Iriya K, Carrilho FJ. No correlation of babA2 with vacA and cagA genotypes of Helicobacter pylori and grading of gastritis from peptic ulcer disease patients in Brazil. Helicobacter. 2005;10:601–8.PubMedCrossRef
23.
Erzin Y, Koksal V, Altun S, Dobrucali A, Aslan M, Erdamar S, Dirican A, Kocazeybek B. Prevalence of Helicobacter pylori vacA, cagA, cagE, iceA, babA2 genotypes and correlation with clinical outcome in Turkish patients with dyspepsia. Helicobacter. 2006;11:574–80.PubMedCrossRef
24.
Mottaghi B, Safaralizadeh R, Bonyadi M, Latifi-Navid S, Somi MH (2014) Helicobacter pylori vacA i region polymorphism but not babA2 status associated to gastric cancer risk in northwestern Iran. Clin Exp Med (ahead of print).
25.
Kim SY, Woo CW, Lee YM, Son BR, Kim JW, Chae HB, Youn SJ, Park SM. Genotyping CagA, VacA subtype, IceA1, and BabA of Helicobacter pylori isolates from Korean patients, and their association with gastroduodenal diseases. J Korean Med Sci. 2001;16:579–84.PubMedPubMedCentralCrossRef
26.
Lai CH, Kuo CH, Chen YC, Chao FY, Poon SK, Chang CS, Wang WC. High prevalence of cagA and babA2 positive Helicobacter pylori clinical isolates in Taiwan. J Clin Microbiol. 2002;40:3860–2.PubMedPubMedCentralCrossRef
27.
Torres L, Melian K, Moreno A, Alonso J, Sabatier C, Hernandez M, Bermudez L, Rodriguez B. Prevalence of vacA, cagA and babA2 genes in Cuban Helicobacter pylori isolates. World J Gastroenterol. 2009;15:204–10.PubMedPubMedCentralCrossRef
28.
Yamaoka Y, Kodama T, Kashima K, Graham DY, Sepulveda AR. Variants of the 3′ region of the cagA gene in Helicobacter pylori isolates from patients with different H. pylori-associated diseases. J Clin Microbiol. 1998;36:2258–63.PubMedPubMedCentral
29.
Blaser MJ, Perez-Perez GI, Kleanthous H, Cover TL, Peek RM, Chyou PH, Stemmermann GN, Nomura A. Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach. Cancer Res. 1995;55:2111–5.PubMed
30.
Queiroz DM, Mendes EN, Carvalho AST, Rocha GA, Oliveira AMR, Soares TF, Santos A, Cabral MMDA, Nogueira AMMF. Factors associated with Helicobacter pylori infection by a cagA-positive strain in children. J Infect Dis. 2000;181:626–30.PubMedCrossRef
31.
Yamaoka Y, Kato M, Asaka M. Geographic differences in gastric cancer incidence can be explained by differences between Helicobacter pylori strains. Intern Med. 2008;47:1077–83.PubMedPubMedCentralCrossRef
32.
Saxena A, Shukla S, Prasad KN, Ghoshal UC. Virulence attributes of Helicobacter pylori isolates & their association with gastroduodenal disease. Indian J Med Res. 2011;133:514–20.PubMedPubMedCentral
33.
34.
Olfat FO, Zheng Q, Oleastro M, Voland P, Borén T, Karttunen R, Engstrand L, Rad R, Prinz C, Gerhard M. Correlation of the Helicobacter pylori adherence factor BabA with duodenal ulcer disease in four European countries. FEMS Immunol Med Microbiol. 2005;44:151–6.PubMedCrossRef
35.
Gatti LL, Modena JL, Payao SL, Smith Mde A, Fukuhara Y, Módena JL, de Oliveira RB, Brocchi M. Prevalence of Helicobacter pylori cagA, iceA and babA2 alleles in Brazilian patients with upper gastrointestinal diseases. Acta Trop. 2006;100:232–40.PubMedCrossRef
36.
Chomvarin C, Namwat W, Chaicumpar K, Mairianq P, Sangchan A, Sripa B, Tor-Udam S, Vilaichone RK. Prevalence of Helicobacter pylori vacA, cagA, cagE, iceA and babA2 genotypes in Thai dyspeptic patients. Int J Infect Dis. 2008;12:30–6.PubMedCrossRef
37.
Erzin Y, Koksal V, Altun S, Dobrucali A, Aslan M, Erdamar S, Goksel S, Dirican A, Kocazeybek B. Role of host interleukin 1beta gene (IL-1B) and interleukin 1 receptor antagonist gene (IL-1RN) polymorphisms in clinical outcomes in Helicobacter pylori-positive Turkish patients with dyspepsia. J Gastroenterol. 2008;43:705–10. doi:10.​1007/​s00535-008-2220-7.PubMedCrossRef
38.
Azevedo M, Eriksson S, Mendes N, Serpa J, Resende LP, Ruvoen-Clouet N, Haas R, Boren T, Le Pendu J, David L. Infection by Helicobacter pylori expressing the BabA adhesin is influenced by the secretor phenotype. J Pathol. 2008;215:308–16. doi:10.​1002/​path.​2363.PubMedCrossRef
39.
40.
Crabtree JE, Wyatt JI, Trejdosiewicz LK, Peichl P, Nichols PH, Ramsay N, Primrose JN, Lindley IJ. Interleukin-8 expression in Helicobacter pylori infected, normal, and neoplastic gastroduodenal mucosa. J Clin Pathol. 1994;47:61–6.PubMedPubMedCentralCrossRef
41.
42.
Bodger K, Crabtree JE. Helicobacter pylori and gastric inflammation. Br Med Bull. 1998;54:139–50.PubMedCrossRef
43.
Yamaoka Y, Kwon DH, Graham DY. A M(r) 34,000 proinflammatory outer membrane protein (oipA) of Helicobacter pylori. Proc Natl Acad Sci. 2000;97:7533–8.PubMedPubMedCentralCrossRef
44.
Gionchetti P, Vaira D, Campieri M, Holton J, Menegatti M, Belluzzi A, Bertinelli E, Ferretti M, Brignola C, Miglioli M. Enhanced mucosal interleukin-6 and -8 in Helicobacter pylori-positive dyspeptic patients. Am J Gastroenterol. 1994;89:883–7.PubMed
45.
Algood HMS, Cover TL. Helicobacter pylori persistence: an overview of interactions between H. pylori and host immune defenses. Clin Microbiol Rev. 2006;19:597–613.PubMedPubMedCentralCrossRef
46.
47.
48.
Wagner S, Beil W, Westermann J, Logan RP, Bock CT, Trautwein C, Bleck JS, Manns MP. Regulation of gastric epithelial cell growth by Helicobacter pylori: offdence for a major role of apoptosis. Gastroenterology. 1997;113:1836–47.PubMedCrossRef
49.
Rudi J, Kuck D, Strand S, von Herbay A, Mariani SM, Krammer PH, Galle PR, Stremmel W. Involvement of the CD95 (APO-1/Fas) receptor and ligand system in Helicobacter pylori-induced gastric epithelial apoptosis. J Clin Invest. 1998;102:1506–14.PubMedPubMedCentralCrossRef
50.
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;63:1681–7.PubMedPubMedCentral
51.
Fan X, Crowe SE, Behar S, Gunasena H, Ye G, Haeberle H, Van Houten N, Gourley WK, Ernst PB, Reyes VE. The effect of class II major histocompatibility complex expression on adherence of Helicobacter pylori and induction of apoptosis in gastric epithelial cells: a mechanism for T helper cell type 1-mediated damage. J Exp Med. 1998;187:1659–69.PubMedPubMedCentralCrossRef
52.
Akopyanz N, Bukanov NO, Westblom TU, Kresovich S, Berg DE. DNA diversity among clinical isolates of Helicobacter pylori detected by PCR-based RAPD fingerprinting. Nucleic Acid Res. 1992;20:5137–42.PubMedPubMedCentralCrossRef
53.
Achtman M, Azuma T, Berg DE, Ito Y, Morelli G, Pan ZJ, Suerbaum S, Thompson SA, van der Ende A, van Doorn LJ. Recombination and clonal groupings within Helicobacter pylori from different geographical regions. Mol Microbiol. 1999;32:459–70.PubMedCrossRef
54.
Kersulyte D, Mukhopadhyay AK, Velapatiño B, et al. Differences in genotypes of Helicobacter pylori from different human populations. J Bacteriol. 2000;182:3210–8.PubMedPubMedCentralCrossRef
55.
Basso D, Plebani M. H. pylori infection: bacterial virulence factors and cytokine gene polymorphisms as determinants of infection outcome. Crit Rev Clin Lab Sci. 2004;41:313–37.PubMedCrossRef
56.
57.
Keenan JI, Allardyce RA. Iron influences the expression of Helicobacter pylori outer membrane vesicle-associated virulence factors. Eur J Gastroenterol Hepatol. 2000;12:1267–73.PubMedCrossRef
58.
59.
Ausubel FM, Brent R, Kingston RE, Moore DD, Seidman JG, Smith JA, Struhl K. Current Protocols in Molecular Biology. New York: Greene publishing and Wiley-Interscience; 1993.
60.
61.
Zambon CF, Navaglia F, Basso D, Rugge M, Plebani M. Helicobacter pylori babA2, cagA, and s1 vacA genes work synergistically in causing intestinal metaplasia. J Clin Pathol. 2003;56:287–91.PubMedPubMedCentralCrossRef
62.
Chattopadhyay S, Patra R, Ramamurthy T, Chowdhury A, Santra A, Dhali GK, Bhattacharya SK, Berg DE, Nair GB, Mukhopadhyay AK. Multiplex PCR assay for rapid detection and genotyping of Helicobacter pylori directly from biopsy specimens. J Clin Microbiol. 2004;42:2821–4.PubMedPubMedCentralCrossRef
63.
Atherton JC, Cao P, Peek RM Jr, Tummuru MK, Blaser MJ, Cover TL. Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific vacA types with cytotoxin production and peptic ulceration. J Biol Chem. 1995;270:17771–7.PubMedCrossRef
Metadata
Title
Helicobacter pylori strains harboring babA2 from Indian sub population are associated with increased virulence in ex vivo study
Authors
Prachetash Ghosh
Avijit Sarkar
Mou Ganguly
Raghwan
Jawed Alam
Ronita De
Asish K. Mukhopadhyay
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Gut Pathogens / Issue 1/2016
Electronic ISSN: 1757-4749
DOI
https://doi.org/10.1186/s13099-015-0083-z

Other articles of this Issue 1/2016

Gut Pathogens 1/2016 Go to the issue

Research

Serotype epidemiology and multidrug resistance patterns of Salmonella enterica infecting humans in Italy

Genome Report

Whole genome sequencing uncovers a novel IND-16 metallo-β-lactamase from an extensively drug-resistant Chryseobacterium indologenes strain J31

Research

Antimicrobial resistance of Campylobacter isolates from small scale and backyard chicken in Kenya

Research

Genotyping of Salmonella Typhi using 8-loci multi locus VNTR analysis

Letter to the Editor

Bacteriophage infections of microbiota can lead to leaky gut in an experimental rodent model

Research

Genotyping and antibiotic resistance of thermophilic Campylobacter isolated from chicken and pig meat in Vietnam
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits