biostudies-literatureMetz PDutch Research Council (NWO)NCI NIH HHSNational Institutes of Health364https://www.ebi.ac.uk/biostudies/studies/S-EPMC6823872biostudies-literatureUnknown9<b>Objective:</b> The human intestinal microbiome plays an important role in inflammatory bowel disease (IBD) and colorectal cancer (CRC) development. One of the first discovered bacterial mediators involves <i>Bacteroides fragilis</i> toxin (BFT, also named as fragilysin), a metalloprotease encoded by enterotoxigenic <i>Bacteroides fragilis</i> (ETBF) that causes barrier disruption and inflammation of the colon, leads to tumorigenesis in susceptible mice, and is enriched in the mucosa of IBD and CRC patients. Thus, targeted inhibition of BFT may benefit ETBF carrying patients. <b>Design:</b> By applying two complementary <i>in silico</i> drug design techniques, drug repositioning and molecular docking, we predicted potential BFT inhibitory compounds. Top candidates were tested <i>in vitroFrontiers in cellular and infection microbiologyDrug Discovery and Repurposing Inhibits a Major Gut Pathogen-Derived Oncogenic Toxin.PMC6823872R01 CA179440016.166.089864.14.004R01CA179440Sears CLPervaiz MRitschel TMetz PTjan MJHBoleij AHermans SWu SDutilh BEShettigar AfalseDrug Discovery and Repurposing Inhibits a Major Gut Pathogen-Derived Oncogenic Toxin.<b>Objective:</b> The human intestinal microbiome plays an important role in inflammatory bowel disease (IBD) and colorectal cancer (CRC) development. One of the first discovered bacterial mediators involves <i>Bacteroides fragilis</i> toxin (BFT, also named as fragilysin), a metalloprotease encoded by enterotoxigenic <i>Bacteroides fragilis</i> (ETBF) that causes barrier disruption and inflammation of the colon, leads to tumorigenesis in susceptible mice, and is enriched in the mucosa of IBD and CRC patients. Thus, targeted inhibition of BFT may benefit ETBF carrying patients. <b>Design:</b> By applying two complementary <i>in silico</i> drug design techniques, drug repositioning and molecular docking, we predicted potential BFT inhibitory compounds. Top candidates were tested <i>in vitro2019-01-01T00:00:00Z20192026-04-07T14:30:53.81Z2019-11-15T08:04:42ZS-EPMC68238723170919610.3389/fcimb.2019.00364