Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 21, 2017; 23(11): 1980-1989
Published online Mar 21, 2017. doi: 10.3748/wjg.v23.i11.1980
Effect of treatment failure on the CagA EPIYA motif in Helicobacter pylori strains from Colombian subjects
Javier Andres Bustamante-Rengifo, Andres Jenuer Matta, Alvaro Jairo Pazos, Luis Eduardo Bravo
Javier Andres Bustamante-Rengifo, Department of Microbiology, School of Basic Science, Universidad del Valle, Cali 760043, Colombia
Andres Jenuer Matta, Luis Eduardo Bravo, Registro Poblacional de Cáncer de Cali, Department of Pathology, School of Medicine, Universidad del Valle, Cali 760043, Colombia
Alvaro Jairo Pazos, Department of Biology, Universidad de Nariño, Pasto 520002, Colombia
Author contributions: All the authors that were involved in the acquisition and interpretation of the results read and approved the final manuscript; Bustamante-Rengifo JA, Matta AJ and Pazos AJ conducted the microbiological and molecular tests; Bustamante-Rengifo JA and Bravo LE analyzed the data; Bustamante-Rengifo JA, Pazos AJ, Matta JA and Bravo LE wrote, edited, and revised the manuscript.
Institutional review board statement: All procedures involving human participants were reviewed and approved by the Ethics Committee at Universidad del Valle, Cali, Colombia.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that there is no conflict of interest related to this study.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at javierandres.bustamante@gmail.com Participants gave informed consent for data sharing.
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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Javier Andres Bustamante-Rengifo, MSc, PhD, Department of Microbiology, School of Basic Science, Universidad del Valle, Street 4B N0 36-00, Building 116, Floor 5, Cali 760043, Colombia. javierandres.bustamante@gmail.com
Telephone: +57-2-3006094440 Fax: +57-2-6670329
Received: October 26, 2016
Peer-review started: October 27, 2016
First decision: November 9, 2016
Revised: December 16, 2016
Accepted: February 8, 2017
Article in press: February 8, 2017
Published online: March 21, 2017
Processing time: 144 Days and 7.7 Hours
Abstract
AIM

To evaluate effect of treatment failure on cagA and vacA genotypes in Helicobacter pylori (H. pylori) isolates from Colombia.

METHODS

One hundred and seventy-six participants infected with H. pylori from Colombia were treated during 14 d with the triple-standard therapy. Six weeks later, eradication was evaluated by 13C-Urea breath test. Patients with treatment failure were subjected to endoscopy control; biopsies obtained were used for histopathology and culture. DNA from H. pylori isolates was amplified using primers specific for cagA and vacA genes. The phylogenetic relationships among isolates obtained before and after treatment were established by conglomerate analysis based on random amplified polymorphic DNA (RAPD) fingerprinting.

RESULTS

Treatment effectiveness was at 74.6%. Of the participants with treatment failure, 25 accepted subjected to a second endoscopy. Prevalence of post-treatment infection was 64% (16/25) and 40% (10/25) by histology and culture, respectively. Upon comparing the cagA and vacA genotypes found before and after therapy, multiple cagA genotypes (cagA-positive and cagA-negative) were found before treatment; in contrast, cagA-negative genotypes decreased after treatment. vacA s1m1 genotype was highly prevalent in patients before and after therapy. The 3’cagA region was successfully amplified in 95.5% (21/22) of the isolates obtained before and in 81.8% (18/22) of the isolates obtained after treatment. In the isolates obtained from patients with treatment failure, it was found that 72.7% (16/22) presented alterations in the number of EPIYA motifs, compared to isolates found before treatment.

CONCLUSION

Unsuccessful treatment limits colonization by low-virulence strains resulting in partial and selective eradication in mixed infections, and acts on the cagA-positive strains inducing genetic rearrangements in cagA variable region that produces a loss or gain of EPIYA repetitions.

Keywords: Helicobacter pylori; RAPD-PCR; Treatment failure; EPIYA motifs; 3’cagA variable region

Core tip: This study evaluated the effect of treatment failure on cagA and vacA genotypes in Helicobacter pylori (H. pylori) isolates. It was found, that unsuccessful treatment of H. pylori limits the colonization by low-virulence strains, resulting in partial and selective eradication in mixed infections. Also, acts on the cagA-positive strains inducing genetic rearrangements (deletion or acquisition of EPIYA motifs) that could alter the adherence of CagA protein to the epithelial cell membrane, the level of tyrosine phosphorylation and CagA multimerization, impacting its effects on cellular signaling. Finally, in some cases, may lead to the divergence of H. pylori cagA-positive sub-clones.