TY - JOUR
T1 - Heparin interacts with elongation factor 1α of Cryptosporidium parvum and inhibits invasion
AU - Inomata, Atsuko
AU - Murakoshi, Fumi
AU - Ishiwa, Akiko
AU - Takano, Ryo
AU - Takemae, Hitoshi
AU - Sugi, Tatsuki
AU - Recuenco, Frances Cagayat
AU - Horimoto, Taisuke
AU - Kato, Kentaro
N1 - Funding Information:
We thank Susan Watson for editing the manuscript. We also thank Dr. Kenji Yagita (Protozoa Laboratory, Department of Parasitology, National Institute of Infectious Diseases) for providing us with C. parvum oocysts. This study was supported by Grants-in-Aids for Young Scientists, Exploratory Scientific Research on Innovative Areas (3308) from the Ministry of Education, Culture, Science, Sports, and Technology (MEXT) and for Research on global health issues from the Ministry of Health, Labour and Welfare of Japan, the Bio-oriented Technology Research Advancement Institution (BRAIN), The Akiyama Life Science Foundation, and the Program to Disseminate Tenure Tracking System from the Japan Science and Technology Agency (JST).
PY - 2015/7/1
Y1 - 2015/7/1
N2 - 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.
AB - 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.
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U2 - 10.1038/srep11599
DO - 10.1038/srep11599
M3 - Article
C2 - 26129968
AN - SCOPUS:84934758065
VL - 5
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 11599
ER -
