Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 28, 2023; 29(32): 4860-4872
Published online Aug 28, 2023. doi: 10.3748/wjg.v29.i32.4860
Linolenic acid-metronidazole inhibits the growth of Helicobacter pylori through oxidation
Wen-Ting Zhou, Yuan-Yuan Dai, Li-Juan Liao, Shi-Xian Yang, Hao Chen, Liang Huang, Juan-Li Zhao, Yan-Qiang Huang
Wen-Ting Zhou, Li-Juan Liao, Liang Huang, Juan-Li Zhao, School of Basic Medicine, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
Yuan-Yuan Dai, School of Basic Medicine, Youjiang Medical University for Nationalities, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
Shi-Xian Yang, Department of Laboratory, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
Hao Chen, School of Basic Medicine, Department of Pathology, Wannan Medical College, Wuhu 533000, Anhui Province, China
Liang Huang, Key Laboratory of the Prevention and Treatment of Drug Resistant Microbial Infecting, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
Yan-Qiang Huang, School of Basic Sciences, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
Author contributions: Zhou WT and Dai YY consulted literature, performed experiments, collected and analyzed data and wrote the first draft, making equal contributions to this work; Liao LJ, Yang SX, and Chen H corrected it; Zhao LJ, Huang YQ, and Huang L designed, checked, modified, and completed the manuscript, making equal contributions to this work as co-corresponding authors; Huang L is the first corresponding author; and all authors approved the final version of the article.
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: All the authors report no relevant conflicts of interest for this article.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Liang Huang, Instructor, Key Laboratory of the Prevention and Treatment of Drug Resistant Microbial Infecting, Youjiang Medical University for Nationalities, No. 98 Chengxiang Road, Baise 533000, Guangxi Zhuang Autonomous Region, China. youyihuangl@163.com
Received: May 31, 2023
Peer-review started: May 31, 2023
First decision: July 8, 2023
Revised: July 15, 2023
Accepted: July 31, 2023
Article in press: July 31, 2023
Published online: August 28, 2023
Abstract
BACKGROUND

Resistance to antibiotics is one the main factors constraining the treatment and control of Helicobacter pylori (H. pylori) infections. Therefore, there is an urgent need to develop new antimicrobial agents to replace antibiotics. Our previous study found that linolenic acid-metronidazole (Lla-Met) has a good antibacterial effect against H. pylori, both antibiotic-resistant and sensitive H. pylori. Also, H. pylori does not develop resistance to Lla-Met. Therefore, it could be used for preparing broad-spectrum antibacterial agents. However, since the antibacterial mechanism of Lla-Met is not well understood, we explored this phenomenon in the present study.

AIM

To understand the antimicrobial effect of Lla-Met and how this could be applied in treating corresponding infections.

METHODS

H. pylori cells were treated with the Lla-Met compound, and the effect of the compound on the cell morphology, cell membrane permeability, and oxidation of the bacteria cell was assessed. Meanwhile, the differently expressed genes in H. pylori in response to Lla-Met treatment were identified.

RESULTS

Lla-Met treatment induced several changes in H. pylori cells, including roughening and swelling. In vivo experiments revealed that Lla-Met induced oxidation, DNA fragmentation, and phosphatidylserine ectropionation in H. pylori cells. Inhibiting Lla-Met with L-cysteine abrogated the above phenomena. Transcriptome analysis revealed that Lla-Met treatment up-regulated the expression of superoxide dismutase SodB and MdaB genes, both anti-oxidation-related genes.

CONCLUSION

Lla-Met kills H. pylori mainly by inducing oxidative stress, DNA damage, phosphatidylserine ectropionation, and changes on cell morphology.

Keywords: Helicobacter pylori, Oxidation, Superoxide dismutase, SodB genes, MdaB genes

Core Tip: The clarithromycin resistant Helicobacter pylori (H. pylori) is listed by the World Health Organization as the priority bacteria in urgent need of developing new antibiotics. Our previous research found that linolenic acid-metronidazole has a good antibacterial effect on H. pylori and is not easy to develop drug resistance. Therefore, we further explored its antibacterial mechanism against H. pylori. It was found that it mainly kills H. pylori by inducing oxidative stress, DNA damage, phosphatidylserine ectropionation, and changes on cell morphology. This study may provide a theoretical basis for the development and application of new anti H. pylori lead compound.