Parasite Glycobiology:A Bittersweet Symphony

Human infections caused by parasitic protozoans and helminths are among the world's leading causes of death. More than a million people die each year from diseases like malaria and neglected tropical diseases like leishmaniasis, trypanosomiasis, and schistosomiasis. Patients also endure disabilities that cause lifelong suffering and that affect productivity and development [1]. More insidiously, parasites generate important economic losses, since they often also infect commercially valuable animals. Worldwide, exposure to parasites is increasing due to growing international travel and migrations, as well as climate changes, which affect the geographic distribution of the parasite vectors. The parasitic threat is also aggravated by the rise of the immunocompromised population, which is particularly sensitive to parasite infections (e.g., individuals with AIDS and other immunodeficiencies). A common feature of protozoan parasites and helminths is the synthesis of glycoconjugates and glycan-binding proteins for protection and to interact and respond to changes in their environment. To address the many challenges associated with the study of the structure, the biosynthesis, and the biology of parasitic glycans, the authors of this article have established GlycoPar, a European Marie Curie training program steered by some of the world's academic leaders in the field of parasite glycobiology, in close association with European industrial enterprises. The main scientific goal of this network is the description of novel paradigms and models by which parasite glycoconjugates play a role in the successful colonization of the different hosts. By means of a training-through-research program, the aim of the network is to contribute to the training of a generation of young scientists capable of tackling the challenges posed by parasite glycobiology

A role for heparan sulfate proteoglycans in Plasmodium falciparum sporozoite invasion of anopheline mosquito salivary glands

HS (heparan sulfate) has been shown to be an important mediator of Plasmodium sporozoite homing and invasion of the liver, but the role of this glycosaminoglycan in mosquito vector host–sporozoite interactions is unknown. We have biochemically characterized the function of AgOXT1 (Anopheles gambiae peptide-O-xylosyltransferase 1) and confirmed that AgOXT1 can modify peptides representing model HS and chondroitin sulfate proteoglycans in vitro. Moreover, we also demonstrated that the mosquito salivary gland basal lamina proteoglycans are modified by HS. We used RNA interference-mediated knockdown of HS biosynthesis in A. gambiae salivary glands to determine whether Plasmodium falciparum sporozoites that are released from mosquito midgut oocysts use salivary gland HS as a receptor for tissue invasion. Our results suggest that salivary gland basal lamina HS glycosaminoglycans only partially mediate midgut sporozoite invasion of this tissue, and that in the absence of HS, the presence of other surface co-receptors is sufficient to facilitate parasite entry

Mass spectrometric analysis of the immunodominant glycan epitope of Echinococcus granulosus antigen Ag5

In previous work we showed that Ag5, a major diagnostic antigen from the metacestode of Echinococcus granulosus, possesses a dominant sugar epitope that upon removal results in abolition of most of the antigen immunoreactivity with patient sera. Analysis of this glycan modification has now been performed by western blotting and mass spectrometry. Reactivity to both a specific monoclonal antibody (TEPC15) and human C-reactive protein as well as the presence of a modification of 165 mass units, as detected by mass spectrometry of both glycopeptides and released N-glycans, indicated that the immunodominant sugar epitope of the Ag5 38 kDa subunit is a biantennary structure modified by phosphorylcholine. We believe this is the first time that such a modification has been proven in cestodes and provides the structural basis for understanding the antigenicity of this major E. granulosus component

UDP-xylose and UDP-galactose synthesis in Trichomonas vaginalis

The presence of xylose and galactose residues in the structure of trichomonad lipoglycans was indicated by previous studies and the modification of any glycoconjugate with either monosaccharide requires the respective presence of the nucleotide sugars, UDP-xylose and UDP-galactose. Biosynthesis of UDP-xylose de novo is mediated by UDP-xylose synthase (UXS; UDP-glucuronic acid decarboxylase), which converts UDP-glucuronic acid to UDP-xylose, whereas UDP-galactose can be generated from UDP-glucose by UDP-galactose epimerases (GalE). Trichomonas vaginalis cDNAs, encoding proteins with homology to these enzymes from other eukaryotes, were isolated. The recombinant T. vaginalis UDP-xylose synthase and UDP-galactose epimerase were expressed in Escherichia coli and tested via high pressure liquid chromatography to demonstrate their enzymatic activities. Thereby, in this first report on enzymes involved in glycoconjugate biosynthesis in this organism, we demonstrate the existence of xylose and galactose synthesising pathways in T. vaginalis