Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 28, 2021; 27(24): 3595-3608
Published online Jun 28, 2021. doi: 10.3748/wjg.v27.i24.3595
Early genetic diagnosis of clarithromycin resistance in Helicobacter pylori
Xiao-Hua Li, Yong-Yi Huang, Lin-Ming Lu, Li-Juan Zhao, Xian-Ke Luo, Ru-Jia Li, Yuan-Yuan Dai, Chun Qin, Yan-Qiang Huang, Hao Chen
Xiao-Hua Li, Yong-Yi Huang, Li-Juan Zhao, Ru-Jia Li, Yuan-Yuan Dai, Chun Qin, Yan-Qiang Huang, Research Center for the Prevention and Treatment of Drug Resistant Microbial Infection, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
Lin-Ming Lu, Hao Chen, Department of Pathology, Wannan Medical College, Wuhu 241002, Anhui Province, China
Xian-Ke Luo, Department of Gastroenterology, National Hospital of Guangxi Zhuang Autonomous Region, Nanning Guangxi Zhuang Autonomous Region, 530001, China
Author contributions: Li XH and Huang YY contributed equally to this work, and they consulted the literature, performed the experiments, acquired and analyzed the data, and wrote the first draft; Lu LM, Zhao LJ, Luo XK, Li RJ, Dai YY, and Qin C revised the manuscript; Huang YQ and Chen H served as corresponding authors, contributed equally to this work, contributed equally to this work, and they designed, checked, and revised the final manuscript; all authors approved the final version of the article.
Supported by National Natural Science Foundation of China, No. 81760739 and No. 31460023; and Special Fund Projects for Guiding Local Science and Technology Development by the Chinese Government, No. GUIKEZY20198004.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board at Youjiang Medical University for Nationalities.
Conflict-of-interest statement: Li XH, Huang YY, Zhao LJ, Li RJ, Dai YY, Qin C, and Huang YQ are employed by Youjiang Medical University for Nationalities; Lu LM and Chen H are employed by Wannan Medical College; Luo XK is employed by National Hospital of Guangxi Zhuang Autonomous Region; all other authors have nothing to disclose.
Data sharing statement: No additional data are available.
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yan-Qiang Huang, MD, PhD, Professor, Research Center for the Prevention and Treatment of Drug Resistant Microbial Infection, Youjiang Medical University for Nationalities, No. 98 Countryside Road, Baise 533000, Guangxi Zhuang Autonomous Region, China, hyq77615@163.com
Received: March 2, 2021
Peer-review started: March 2, 2021
First decision: April 5, 2021
Revised: April 13, 2021
Accepted: May 21, 2021
Article in press: May 21, 2021
Published online: June 28, 2021
ARTICLE HIGHLIGHTS
Research background

Helicobacter pylori (H. pylori) is recognized as an important human pathogen associated with superficial gastritis, atrophic gastritis, gastric cancer, etc., each of which has become a serious threat to human health and survival. The rate of drug resistance is increasing due to the wide use of antibiotics and high rates of resistance to clarithromycin, metronidazole, and levofloxacin are associated with the failure of H. pylori eradication. At present, the mechanism of antibiotic resistance of H. pylori is not completely understood. It is very difficult to prevent drug resistance and improve the rate of eradication of the target, thus warranting exploration of the mechanism of drug resistance to H. pylori, and provision of an experimental basis for the prevention and treatment of drug resistance.

Research motivation

Clarithromycin-resistant H. pylori urgently needs new antibiotics; however, antibiotic research and development are very difficult. If we can detect drug resistance by detecting drug-resistant genes in a timeous manner, this may help to alleviate the problem of clarithromycin resistance.

Research objectives

The objectives of this study were to investigate drug-resistant genes in H. pylori, and find a gene suited to early diagnosis of clarithromycin resistance, thereby rationalizing the rate of use of the drug.

Research methods

H. pylori strains were isolated and cultured, minimal inhibitory concentrations were measured, and complete genome sequence was determined. Prediction and analysis of the function of drug-resistant genes indicated that the RNA expression of hp1181 and hp1184 increased in the H. pylori strains, which was the same in the artificially induced clarithromycin-resistant bacteria. The relationships between hp1181 or hp1184 and clarithromycin resistance were confirmed with gene mutant and drug-resistant strains.

Research results

Hp1181 and hp1184 genes were found in these H. pylori strains. Their expression was associated with clarithromycin resistance.

Research conclusions

Hp1181 and hp1184 mutations may be the earliest and most persistent response to clarithromycin resistance, and they may be the main target genes for the diagnosis, prevention, and treatment of clarithromycin resistance.

Research perspectives

The relationship between hp1181 or hp1184 and clarithromycin resistance was demonstrated, providing an improved experimental basis for early diagnosis of clarithromycin resistance in H. pylori.