Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 7, 2018; 24(9): 971-981
Published online Mar 7, 2018. doi: 10.3748/wjg.v24.i9.971
Can bacterial virulence factors predict antibiotic resistant Helicobacter pylori infection?
Denise E Brennan, Colin Dowd, Colm O’Morain, Deirdre McNamara, Sinéad M Smith
Denise E Brennan, Colin Dowd, Colm O’Morain, Deirdre McNamara, Sinéad M Smith, Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin D2, Ireland
Author contributions: McNamara D and Smith SM contributed equally to the study; McNamara D and Smith SM designed the study and coordinated the research; Brennan DE, Dowd C and Smith SM performed experiments and analysed data; O’Morain C and McNamara D recruited patients; Brennan DE, McNamara D and Smith SM wrote the paper; all authors provided critical input into the final manuscript.
Supported by the Health Research Board (HRA-POR-2014-526).
Institutional review board statement: The study was reviewed and approved by the Adelaide and Meath Hospital Research Ethics Committee.
Conflict-of-interest statement: None to declare.
Data sharing statement: There is no additional data to share.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Sinéad M Smith, PhD, Ussher Assistant Professor in Applied and Translational Medicine, Rm 1.46, Department of Clinical Medicine, Trinity Centre, Adelaide and Meath Hospital, Tallaght, Dublin D24, Ireland.
Telephone: +353-1-8963844 Fax: +353-1-8962988
Received: January 10, 2018
Peer-review started: January 10, 2018
First decision: January 18, 2018
Revised: February 5, 2018
Accepted: February 8, 2018
Article in press: February 8, 2018
Published online: March 7, 2018

To evaluate the association between virulence factor status and antibiotic resistance in Helicobacter pylori (H. pylori)-infected patients in Ireland.


DNA was extracted from antral and corpus biopsies obtained from 165 H. pylori-infected patients. Genotyping for clarithromycin and fluoroquinolone-mediating mutations was performed using the Genotype HelicoDR assay. cagA and vacA genotypes were investigated using PCR.


Primary, secondary and overall resistance rates for clarithromycin were 50.5% (n = 53/105), 78.3% (n = 47/60) and 60.6% (n = 100/165), respectively. Primary, secondary and overall resistance rates for fluoroquinolones were 15.2% (n = 16/105) and 28.3% (n = 17/60) and 20% (n = 33/165), respectively. Resistance to both antibiotics was 12.4% (n = 13/105) in treatment-naïve patients, 25% (n = 15/60) in those previously treated and 17% (n = 28/165) overall. A cagA-positive genotype was detected in 22.4% (n = 37/165) of patient samples. The dominant vacA genotype was S1/M2 at 44.8% (n = 74/165), followed by S2/M2 at 26.7% (n = 44/165), S1/M1 at 23.6% (n = 39/165) and S2/M1 at 4.8% (n = 8/165). Primary clarithromycin resistance was significantly lower in cagA-positive strains than in cagA-negative strains [32% (n = 8/25) vs 56.3% (n = 45/80) P = 0.03]. Similarly, in patients infected with more virulent H. pylori strains bearing the vacA s1 genotype, primary clarithromycin resistance was significantly lower than in those infected with less virulent strains bearing the vacA s2 genotype, [41% (n = 32/78) vs 77.8% (n = 21/27) P = 0.0001]. No statistically significant association was found between primary fluoroquinolone resistance and virulence factor status.


Genotypic H. pylori clarithromycin resistance is high and cagA-negative strains are dominant in our population. Less virulent (cagA-negative and vacA S2-containing) strains of H. pylori are associated with primary clarithromycin resistance.

Keywords: Helicobacter pylori, Antibiotic resistance, Fluoroquinolone, Clarithromycin, Virulence factor, VacA, CagA

Core tip: The management of Helicobacter pylori (H. pylori) infection is challenging, largely due to the emergence of antibiotic resistance. A greater understanding of local antibiotic resistance rates is important in determining the most appropriate treatment regimen in a given population. Furthermore, insight into the virulence of the infecting strains and the association between virulence and antibiotic resistance could potentially be an avenue to explore in the effort to improve eradication rates. This study provides and update on the prevalence of clarithromycin and fluoroquinolone resistance in Ireland and demonstrates that less virulent strains of H. pylori are predictive of primary clarithromycin resistance.