Cholestenone functions as an antibiotic against Helicobacter pylori by inhibiting biosynthesis of the cell wall component CGL

Significance Cholesteryl-α-D-glucopyranoside (CGL) is a cell wall constituent ofHelicobacter pylori . It is synthesized by cholesterol α-glucosyltransferase, which transfers glucose from UDP-glucose to a carbon atom at the third position of cholesterol with an α1,3-linkage. We previously discovered that αGlcNAc contained in gastric gland mucins serves as antibiotic againstH. pylori by inhibiting CGL biosynthesis. Here, we reveal that cholestenone exhibits antibiotic activity againstH. pylori including a clarithromycin-resistantH. pylori strain by suppressing CGL biosynthesis in vitro. Strikingly, oral administration of cholestenone alone successfully eradicatedH. pylori infection in C57BL/6 mice. Given its safety, cholestenone therapy could be promising to eradicateH. pylori , including antibiotic-resistant strains.