title: Heparin interacts with elongation factor 1α of Cryptosporidium parvum and inhibits invasion.
abstract: Cryptosporidium parvum is an apicomplexan parasite that can cause serious watery diarrhea, cryptosporidiosis, in human and other mammals. C. parvum invades gastrointestinal epithelial cells, which have abundant glycosaminoglycans on their cell surface. However, little is known about the interaction between C. parvum and glycosaminoglycans. In this study, we assessed the inhibitory effect of sulfated polysaccharides on C. parvum invasion of host cells and identified the parasite ligands that interact with sulfated polysaccharides. Among five sulfated polysaccharides tested, heparin had the highest, dose-dependent inhibitory effect on parasite invasion. Heparan sulfate-deficient cells were less susceptible to C. parvum infection. We further identified 31 parasite proteins that potentially interact with heparin. Of these, we confirmed that C. parvum elongation factor 1α (CpEF1α), which plays a role in C. parvum invasion, binds to heparin and to the surface of HCT-8 cells. Our results further our understanding of the molecular basis of C. parvum infection and will facilitate the development of anti-cryptosporidial agents.
authors.affiliation: Department of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Inomata
authors.affiliation: 1] Department of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan [2] National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan.
authors.forename: Fumi
authors.initials: F
authors.lastname: Murakoshi
authors.affiliation: 1] Department of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan [2] National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Ishiwa
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Takano
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takemae
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan.
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Sugi
authors.affiliation: 1] Department of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan [2] National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan.
authors.forename: Frances
authors.initials: F
authors.lastname: Cagayat Recuenco
authors.affiliation: Department of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Horimoto
authors.affiliation: 1] Department of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan [2] National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kato
mesh_terms: D000818:Animals; D016466:CHO Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D002853:Chromatography, Liquid; D003412:Cricetulus; D016785:Cryptosporidium parvum / Q000187:drug effects / Q000472:pathogenicity*; D004591:Electrophoresis, Polyacrylamide Gel; D006493:Heparin / Q000494:pharmacology*; D006790:Host-Parasite Interactions / Q000187:drug effects; D015151:Immunoblotting; D008024:Ligands; D008819:Mice, Nude; D020648:Peptide Elongation Factor 1 / Q000378:metabolism*; D011134:Polysaccharides / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000378:metabolism; D016622:Silver Staining; D034101:Sporozoites / Q000187:drug effects / Q000502:physiology; D013431:Sulfates / Q000494:pharmacology*; D053719:Tandem Mass Spectrometry
chemical_list: D008024:Ligands; D020648:Peptide Elongation Factor 1; D011134:Polysaccharides; D011994:Recombinant Proteins; D013431:Sulfates; D006493:Heparin