Published online Aug 28, 2023. doi: 10.3748/wjg.v29.i32.4860
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
Processing time: 86 Days and 4.5 Hours
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.
Currently, there is a serious drug resistance situation in H. pylori and new antibiotics are urgently needed; however, antibiotic research and development are very difficult. If we can understand the antibacterial mechanism of linolenic acid-metronidazole (Lla-Met), we can better apply it to antimicrobial treatment and solve the problem of antibiotic resistance.
The objectives of this study were to confirm the antibacterial effect of Lla-Met on H. pylori, and to provide theoretical support for further research and development of Lla-Met as an anti-H. pylori drug, and to help overcome the resistance of H. pylori to existing antibiotic drugs.
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 by scanning electron microscope, propidium iodide staining, FIFC-FD, detection of ion channels, detection of intracellular reactive oxygen species, and detection of phosphatidylserine ectropion. Meanwhile, the differently expressed genes in H. pylori in response to Lla-Met treatment were identified by transcriptome sequencing and quantitative real-time polymerase chain reaction.
The expression of both SodB and MdaB genes was up-regulated after treatment with Lla-Met, and both genes are associated with antioxidants. Lla-Met inhibits the growth of H. pylori through oxidation.
The mechanism of linoleic-metronidazole compound was demonstrated to involve inhibiting H. pylori growth by inducing excessive reactive oxygen species accumulation, resulting in excessive superoxide dismutase MdaB and SodB genes expression.
This study proves the antibacterial effect of Lla-Met on H. pylori at the molecular level, providing theoretical support for further research and development of Lla-Met as an anti-H. pylori drug to help overcome H. pylori resistance to current antibiotic drugs.