Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 7, 2020; 26(45): 7118-7130
Published online Dec 7, 2020. doi: 10.3748/wjg.v26.i45.7118
Discovery of unique African Helicobacter pylori CagA-multimerization motif in the Dominican Republic
Takaaki Ono, Modesto Cruz, Hiroyuki Nagashima, Phawinee Subsomwong, Junko Akada, Takashi Matsumoto, Tomohisa Uchida, Rumiko Suzuki, Celso Hosking, José A Jiménez Abreu, Yoshio Yamaoka
Takaaki Ono, Phawinee Subsomwong, Junko Akada, Takashi Matsumoto, Rumiko Suzuki, Yoshio Yamaoka, Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu 879-5593, Japan
Takaaki Ono, Criminal Investigation Laboratory, Oita Prefectural Police Headquarters, Oita 870-1117, Japan
Modesto Cruz, Celso Hosking, Institute of Microbiology and Parasitology, IMPA, Faculty of Science, Autonomous University of Santo Domingo, Santo Domingo 10103, Dominican Republic
Modesto Cruz, Department of Biomedical Research, National Institute of Medicine and Diagnostic Imaging, Santo Domingo 10107, Dominican Republic
Hiroyuki Nagashima, Department of Gastroenterology, Hokkaido Cancer Center, Sapporo 003-0804, Japan
Tomohisa Uchida, Department of Molecular Pathology, Oita University Faculty of Medicine, Yufu 879-5593, Japan
José A Jiménez Abreu, Dominican-Japanese Digestive Disease Center, Dr Luis E. Aybar Health and Hygiene City, Santo Domingo 10302, Dominican Republic
Yoshio Yamaoka, Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, TX 77030, United States
Author contributions: Suzuki R, Cruz M and Yamaoka Y conceived and designed the experiments; Ono T, Nagashima H, Subsomwong P and Uchida T performed the experiments; Ono T, Akada J, Matsumoto T, Suzuki R and Yamaoka Y analyzed the data; Cruz M, Hosking C and Jiménez Abreu JA contributed to obtaining the samples; Ono T and Yamaoka Y wrote the manuscript; Yamaoka Y and Cruz M revised the manuscript and added important content.
Supported by The Grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, No. 16H05191, No. 221S0002, No. 16H06279, No. 18KK0266 and No. 19H03473; and (partly) the National Fund for Innovation and Development of Science and Technology from the Ministry of Higher Education Science and Technology of the Dominican Republic, No. 2012-2013-2A1-65 and No. 2015-3A1-182 (MC).
Institutional review board statement: The protocol was reviewed and approved by the Ethics Committees of Dr Luis E. Aybar Health and Hygiene City, the Institute of Microbiology and Parasitology, IMPA, Faculty of Sciences, Autonomous University of Santo Domingo, UASD and The National Council of Bioethics in Health, CONABIOS, in the Dominican Republic and Oita University, Faculty of Medicine, Japan.
Institutional animal care and use committee statement: This study did not contain animal experiments.
Conflict-of-interest statement: No conflicts of interest exist.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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:
Corresponding author: Yoshio Yamaoka, MD, PhD, Doctor, Professor, Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu 879-5593, Japan.
Received: August 1, 2020
Peer-review started: August 1, 2020
First decision: September 30, 2020
Revised: October 10, 2020
Accepted: November 12, 2020
Article in press: November 12, 2020
Published online: December 7, 2020
Research background

Helicobacter pylori (H. pylori) plays an essential role in the development of peptic ulcer disease and gastric cancer. The CagA protein produced by H. pylori is the most studied virulence factor.

Research motivation

Gastric cancer is one of the most common cancers.

Research objectives

The present study aimed to evaluate the correspondence between the CagA-multimerization (CM) motif and phylogeographical classification using multilocus sequence typing (MLST) population structure in H. pylori in the Dominican Republic, which could be helpful to elucidate the African enigma.

Research methods

The Glu-Pro-Ile-Tyr-Ala (EPIYA) pattern and CM motif genotypes were determined using a polymerase chain reaction-based sequencing. The population structure was analyzed using MLST. Peptic ulcer disease and gastric cancer were identified via endoscopy, and gastric cancer was confirmed by histopathology.

Research results

Many CM motifs, which are the amino acid sequences of "FPLRRSAKVEDLSKVG", were found. This type was significantly more frequent in strains classified as hpAfrica1 using MLST analysis (P = 0.034).

Research conclusions

We found the unique African CM motif in the Western-type CagA in the Dominican Republic and termed it Africa1-CM.

Research perspectives

In the future, it is necessary to evaluate the relationship between these various CM motifs and their toxicity by conducting tests such as hummingbird phenotype in vitro.