Antibacterial Effects of Disulfiram in Helicobacter pylori

Tomomi Kobatake; Keiki Ogino; Hiroyuki Sakae; Kazuyoshi Gotoh; Akari Watanabe; Osamu Matsushita; Hiroyuki Okada; Kenji Yokota

doi:10.2147/IDR.S299177

Antibacterial Effects of Disulfiram in Helicobacter pylori

Infect Drug Resist. 2021 May 12:14:1757-1764. doi: 10.2147/IDR.S299177. eCollection 2021.

Authors

Tomomi Kobatake¹, Keiki Ogino², Hiroyuki Sakae³, Kazuyoshi Gotoh⁴, Akari Watanabe⁵, Osamu Matsushita⁴, Hiroyuki Okada³, Kenji Yokota¹

Affiliations

¹ Graduate School of Health Science Okayama University, Okayama, 700-8558, Japan.
² Department of Environmental Medicine, Koch Medical School, Nankoku-shi, 783-8505, Japan.
³ Department of Gastroenterology and Hepatology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, 700-8558, Japan.
⁴ Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, 700-8558, Japan.
⁵ Department of Oral Health Care and Rehabilitation, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 770-8501, Japan.

Abstract

Background: Helicobacter pylori infection poses a risk of the occurrence of gastrointestinal diseases, such as gastric cancer. Its incidence rate is significantly reduced by eradication, and thereby, eradication therapy is generally performed. Disulfiram is an oral prescription drug mainly used for the treatment of alcohol dependence. In recent years, reports have been made on its anticancer and antibacterial effects, and thus, it has recently become an interesting subject. This study aimed to examine the antibacterial activity of disulfiram, investigate the presence or absence of its antibacterial activity on H. pylori, and determine whether it could be a new bactericidal drug against drug-resistant H. pylori.

Materials and methods: Drug-sensitive strains of H. pylori and amoxicillin-resistant, clarithromycin-resistant, and metronidazole-resistant strains were used, and a growth inhibition test of H. pylori using disulfiram was performed. Furthermore, the expression of urease, vacuolating cytotoxin A (VacA), and CagA, the virulence proteins of H. pylori, was quantitatively analyzed using the Western blotting method. In addition, for H. pylori used in this study, the 16SrDNA sequence, a ribosomal gene involved in protein production, was analyzed to examine the presence or absence of gene mutation.

Results: Disulfiram suppressed the growth of 7 out of 12 H. pylori strains at 1 µg/mL, and no correlation was observed between their susceptibility/resistance to current eradication antimicrobial drugs and disulfiram resistance. Disulfiram reduced the expression levels of urease, VacA, and CagA proteins. H. pylori, which showed resistance to disulfiram, tended to have fewer gene deletions/insertions in the 16S rDNA sequence; however, no specific mutation was detected.

Conclusion: Disulfiram has a bactericidal effect on H. pylori at low concentrations, suggesting that it can be used as a supplement for current H. pylori eradication drugs.

Keywords: CagA; Helicobacter pylori; disulfiram; urease; vacuolating toxin.