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.

The Cryptosporidium parvum C-Type Lectin CpClec Mediates Infection of Intestinal Epithelial Cells via Interactions with Sulfated Proteoglycans

“…Recently, Inomata and colleagues reported that sulfated GAGs inhibit C. parvum infection in a dose-dependent manner (24). They also demonstrated binding of heparin to elongation factor 1␣, an adhesin previously implicated in the mediation of C. parvum invasion in vitro (49).…”

“…(18,19), and Toxoplasma gondii (20)(21)(22)(23). Recently, Inomata et al reported that heparin mediates C. parvum invasion in vitro via interaction with elongation factor 1␣ (24). Still, the precise role of GAGs during C. parvum infection and the mechanisms underlying these interactions are poorly understood.…”

Identification of Heparin-binding Proteins on the Cell Surface of <I>Cryptococcus neoformans</I>

“…In bacteria, heparin-binding hemagglutinin (HBHA) in Mycobacterium [7][8][9] , the Fim2 subunit of fimbriae in Bordetella pertussis 10) , and many proteins including metabolic enzymes from Mycoplasma 11) and Staphylococcus aureus 12) have been identified. Among eukaryotic pathogens, heparinbinding motifs in proteins from Candida have been described 13) , as have a Blastomyces adhesin-1 called BAD-1 14) and other heparin-interacting proteins, including an elongation factor of Cryptosporidium 15) . Many of these proteins may have roles in adherence, biofilm formation, invasion, or stress responses.…”

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“…On the other hand, cells deficient in heparan sulfate show less susceptibility to invasion. It is as if you needed a sulfated key and a sulfated lock to open the door [42,43]. Artemisia annua contains 0.4 % of sulfur which is much higher than in most plants [44].…”