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Heparin interacts with elongation factor 1α of Cryptosporidium parvum and inhibits invasion
Atsuko Inomata1, Fumi Murakoshi2, Akiko Ishiwa2
1Department of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
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.
Insights
Sulfated polysaccharides, particularly heparin, inhibit Cryptosporidium parvum invasion of host cells. Researchers identified parasite protein CpEF1α as a key molecule interacting with heparin, offering potential for new anti-cryptosporidial therapies.
Area of Science:
- Parasitology
- Molecular Biology
- Infectious Diseases
Background:
- Cryptosporidium parvum causes watery diarrhea (cryptosporidiosis) in mammals.
- Parasite invasion involves host cell surface glycosaminoglycans, but interactions are poorly understood.
Purpose of the Study:
- To investigate the inhibitory effects of sulfated polysaccharides on C. parvum invasion.
- To identify parasite ligands that bind to sulfated polysaccharides.
Main Methods:
- Screening five sulfated polysaccharides for inhibitory activity against C. parvum invasion.
- Utilizing heparan sulfate-deficient cells to assess infection susceptibility.
- Identifying potential parasite-heparin binding proteins using proteomic approaches.
- Confirming binding of C. parvum elongation factor 1α (CpEF1α) to heparin and host cells.
Main Results:
- Heparin demonstrated the most potent, dose-dependent inhibition of C. parvum invasion.
- Heparan sulfate-deficient cells showed reduced susceptibility to infection.
- Thirty-one parasite proteins potentially interacting with heparin were identified.
- CpEF1α was confirmed to bind heparin and the surface of HCT-8 host cells, playing a role in invasion.
Conclusions:
- Sulfated polysaccharides, especially heparin, can block C. parvum host cell invasion.
- CpEF1α is a novel parasite ligand that interacts with host cell surface molecules.
- Findings advance understanding of C. parvum infection mechanisms and suggest therapeutic targets.
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