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DOI	10.1073/pnas.2016469118
	Cholestenone functions as an antibiotic against Helicobacter pylori by inhibiting biosynthesis of the cell wall component CGL
	Kobayashi J.; Kawakubo M.; Fujii C.; Arisaka N.; Miyashita M.; Sato Y.; Komura H.; Matoba H.; Nakayama J.
发表日期	2021
ISSN	00278424
卷号	118 期号:16
英文摘要	Helicobacter pylori, a pathogen responsible for gastric cancer, contains a unique glycolipid, cholesteryl-α-D-glucopyranoside (CGL), in its cell wall. Moreover, O-glycans having α1,4-linked N-acetylglucosamine residues (αGlcNAc) are secreted from gland mucous cells of gastric mucosa. Previously, we demonstrated that CGL is critical for H. pylori survival and that αGlcNAc serves as antibiotic against H. pylori by inhibiting CGL biosynthesis. In this study, we tested whether a cholesterol analog, cholest-4-en 3-one (cholestenone), exhibits antibacterial activity against H. pylori in vitro and in vivo. When the H. pylori standard strain ATCC 43504 was cultured in the presence of cholestenone, microbial growth was significantly suppressed dose-dependently relative to microbes cultured with cholesterol, and cholestenone inhibitory effects were not altered by the presence of cholesterol. Morphologically, cholestenone-treated H. pylori exhibited coccoid forms. We obtained comparable results when we examined the clarithromycin-resistant H. pylori strain “2460.” We also show that biosynthesis of CGL and its derivatives cholesteryl-6-Otetradecanoyl-α-D-glucopyranoside and cholesteryl-6-O-phosphatidyl-α-D-glucopyranoside in H. pylori is remarkably inhibited in cultures containing cholestenone. Lastly, we asked whether orally administered cholestenone eradicated H. pylori strain SS1 in C57BL/6 mice. Strikingly, mice fed a cholestenone-containing diet showed significant eradication of H. pylori from the gastric mucosa compared with mice fed a control diet. These results overall strongly suggest that cholestenone could serve as an oral medicine to treat patients infected with H. pylori, including antimicrobial-resistant strains. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Antimicrobial resistance; Eradication; Glycolipid; Helicobacter pylori
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179807
作者单位	Department of Molecular Pathology, Shinshu University, School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621, Japan; Department of 2nd Internal Medicine, Shinshu University, School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621, Japan; Department of Biotechnology, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Asahi 3-1-1, Matsumoto, 390-8621, Japan
推荐引用方式 GB/T 7714	Kobayashi J.,Kawakubo M.,Fujii C.,et al. Cholestenone functions as an antibiotic against Helicobacter pylori by inhibiting biosynthesis of the cell wall component CGL[J],2021,118(16).
APA	Kobayashi J..,Kawakubo M..,Fujii C..,Arisaka N..,Miyashita M..,...&Nakayama J..(2021).Cholestenone functions as an antibiotic against Helicobacter pylori by inhibiting biosynthesis of the cell wall component CGL.Proceedings of the National Academy of Sciences of the United States of America,118(16).
MLA	Kobayashi J.,et al."Cholestenone functions as an antibiotic against Helicobacter pylori by inhibiting biosynthesis of the cell wall component CGL".Proceedings of the National Academy of Sciences of the United States of America 118.16(2021).