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

, a pathogen responsible for gastric cancer, contains a unique glycolipid, cholesteryl-α-D-glucopyranoside (CGL), in its cell wall. Moreover, -glycans having α1,4-linked -acetylglucosamine residues (αGlcNAc) are secreted from gland mucous cells of gastric mucosa. Previously, we demonstrated that CGL is critical for survival and that αGlcNAc serves as antibiotic against by inhibiting CGL biosynthesis. In this study, we tested whether a cholesterol analog, cholest-4-en 3-one (cholestenone), exhibits antibacterial activity against in vitro and in vivo. When the 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 exhibited coccoid forms. We obtained comparable results when we examined the clarithromycin-resistant strain "2460." We also show that biosynthesis of CGL and its derivatives cholesteryl-6--tetradecanoyl-α-D-glucopyranoside and cholesteryl-6--phosphatidyl-α-D-glucopyranoside in is remarkably inhibited in cultures containing cholestenone. Lastly, we asked whether orally administered cholestenone eradicated strain SS1 in C57BL/6 mice. Strikingly, mice fed a cholestenone-containing diet showed significant eradication of 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 , including antimicrobial-resistant strains.