Inomata Atsuko, Murakoshi Fumi, Ishiwa Akiko, Takano Ryo, Takemae Hitoshi, Sugi Tatsuki, Cagayat Recuenco Frances, Horimoto Taisuke, Kato Kentaro
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.
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.
Sci Rep. 2015 Jul 1;5:11599. doi: 10.1038/srep11599.
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.
微小隐孢子虫是一种顶复门寄生虫,可在人类和其他哺乳动物中引起严重的水样腹泻,即隐孢子虫病。微小隐孢子虫侵入胃肠道上皮细胞,这些细胞的细胞表面有丰富的糖胺聚糖。然而,关于微小隐孢子虫与糖胺聚糖之间的相互作用知之甚少。在本研究中,我们评估了硫酸化多糖对微小隐孢子虫侵入宿主细胞的抑制作用,并鉴定了与硫酸化多糖相互作用的寄生虫配体。在所测试的五种硫酸化多糖中,肝素对寄生虫侵入具有最高的剂量依赖性抑制作用。硫酸乙酰肝素缺陷细胞对微小隐孢子虫感染的敏感性较低。我们进一步鉴定了31种可能与肝素相互作用的寄生虫蛋白。其中,我们证实了在微小隐孢子虫侵入中起作用的微小隐孢子虫延伸因子1α(CpEF1α)与肝素和HCT-8细胞表面结合。我们的结果进一步加深了我们对微小隐孢子虫感染分子基础的理解,并将促进抗隐孢子虫药物的开发。