title: Effect of vinyl sulfone inhibitors of cysteine proteinases on Tritrichomonas foetus infection.
abstract: Tritrichomonas foetus is a sexually transmitted protozoon that causes genital inflammation and adverse pregnancy outcomes in cattle. Cysteine proteinases (CPs) released by T. foetus degrade immunoglobulin G (IgG) antibodies, complement component 3 and matrix proteins as well as inducing apoptosis of bovine genital epithelial cells. In this study, the efficacies of the vinyl sulfone CP inhibitors K11777 and WRR-483 were tested against CPs of T. foetus. The activity of secreted T. foetus CPs in culture supernatants was decreased in the presence of vinyl sulfone inhibitors. Inhibitor K11777 reduced the in vitro cytopathogenic effects of T. foetus in bovine foetal trophoblast cells, which are relevant target cells since this pathogen interferes with pregnancy. Pre-treatment of T. foetus prior to intravaginal inoculation diminished genital infection in a murine model. Therefore, vinyl sulfone CP inhibitors reduce several effects of T. foetus-secreted CPs, including cytotoxicity on relevant target host cells and genital infection in a murine model. These inhibitors have potential as chemotherapeutic agents against bovine trichomoniasis. Generalisation to human trichomoniasis requires further study.
authors: Department of Pathology, School of Medicine, University of California-San Diego, San Diego, CA, USA.
authors: Eduardo R
authors: ER
authors: Cobo
authors: Sharon L
authors: SL
authors: Reed
authors: Lynette B
authors: LB
authors: Corbeil
mesh_terms: D000818:Animals; D017209:Apoptosis; D018920:Coculture Techniques; D057056:Cysteine Proteases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology; D004789:Enzyme Activation; D005260:Female; D005831:Genital Diseases, Female / Q000188:drug therapy / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009842:Oligopeptides / Q000494:pharmacology; D021261:Parasitic Sensitivity Tests; D010649:Phenylalanine / Q000031:analogs & derivatives; D010879:Piperazines; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000469:parasitology; D013450:Sulfones / Q000494:pharmacology*; D014105:Tosyl Compounds; D014245:Trichomonas Infections / Q000188:drug therapy* / Q000469:parasitology; D016835:Tritrichomonas foetus / Q000187:drug effects / Q000201:enzymology / Q000472:pathogenicity*; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism / Q000469:parasitology; D053058:Trophozoites / Q000187:drug effects / Q000378:metabolism; D014753:Vinyl Compounds / Q000494:pharmacology
chemical_list: D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; C572722:N-methylpiperazine-urea-arginyl-homophenylalanyl-vinylsulfonebenzene; D009842:Oligopeptides; D010879:Piperazines; D013450:Sulfones; D014105:Tosyl Compounds; D014753:Vinyl Compounds; C487484:N-pip-phenylalanine-homophenylalanine-vinyl sulfone phenyl; D010649:Phenylalanine; C009873:divinyl sulfone; D057056:Cysteine Proteases