A comparative study on the heparin‐binding proteomes of Toxoplasma gondii and Plasmodium falciparum

Abstract

Toxoplasma gondii is an obligatory intracellular apicomplexan parasite which exploits host cell surface components in cell invasion and intracellular parasitization. Sulfated glycans such as heparin and heparan sulfate have been reported to inhibit cell invasion by T. gondii and other apicomplexan parasites such as Plasmodium falciparum. The aim of this study was to investigate the heparin-binding proteome of T. gondii. The parasite-derived components were affinity-purified on the heparin moiety followed by MS fingerprinting of the proteins. The heparin-binding proteins of T. gondii and P. falciparum were compared based on functionality and affinity to heparin. Among the proteins identified, the invasion-related parasite ligands derived from tachyzoite/merozoite surface and the secretory organelles were prominent. However, the profiles of the proteins were different in terms of affinity to heparin. In T. gondii, the proteins with highest affinity to heparin were the intracellular components with functions of parasite development contrasted to that of P. falciparum, of which the rhoptry-derived proteins were prominently identified. The profiling of the heparin-binding proteins of the two apicomplexan parasites not only explained the mechanism of heparin-mediated host cell invasion inhibition, but also, to a certain extent, revealed that the action of heparin on the parasite extended after endocytosis.

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

“…gondii infection of host cells has been shown to be both enhanced and inhibited by GAGs at low and high concentrations, respectively (20)(21)(22)(23)48). Similar to P. falciparum, it is reported to contain a large GAG-binding proteome (46), including proteins involved in host cell attachment and invasion, like SAG1 (48), SAG3 (23), and P104 (22), as well as proteins believed to be involved in parasitophorous vacuole formation and intracellular development, like GRA2 (48). The mechanisms underlying the affinities of these proteins for specific GAGs remain poorly understood, but it has been suggested that they involve (i) a combination of glycan composition and sulfate charge and (ii) presentation (21).…”

“…Heparin has been reported to inhibit Plasmodium sp., Babesia sp., and Theileria sergenti growth in vitro and/or in vivo via inhibition of merozoite invasion of erythrocytes (42)(43)(44)(45). P. falciparum is reported to express a large GAG-binding proteome consisting primarily of surface proteins involved in attachment, invasion, and tissue sequestration (44,46). For example, VAR2CSA, a membrane-associated adhesin, binds a lightly sulfated form of chondroitin sulfate A present in the placenta, thereby mediating the establishment of placental malaria (47).…”

Label-Free Quantitative Acetylome Analysis Reveals Toxoplasma gondii Genotype-Specific Acetylomic Signatures

“…The sensitivity of tissue culture and mouse inoculation methods for the demonstration of T. gondii organisms were found to be equal [24]. In addition, many studies prepared tachyzoites using mice inoculation [15,25,26,27,28,29]. The purpose of our research was to investigate acetylomic signatures of different genotypes of Toxoplasma gondii purified in vivo .…”

High sensitivity (zeptomole) detection of BODIPY heparan sulfate (HS) disaccharides by ion-paired RP-HPLC and LIF detection enables analysis of HS from mosquito midguts

“…HIV 1 and Zika virus 2, 3 ) and other cells, including pathogenic microorganisms (e.g. Toxoplasma gondii 4, 5 , Plasmodium falciparum 5, 6 , and Leishmania parasites 7–9 ) and is often involved in the process of infection. In addition, diffusible HS oligosaccharide fragments released by heparanase activity are thought to exert influence further afield 10 .…”

“…Owing to the relatively poor detection sensitivity inherent to carbohydrates compares to other biomolecules, heterogeneous HS chains are isolated from a comparatively large number of cells (typically 10 3 -10 5 cells) or mass of tissue (typically milligrams of starting material). To advance understanding of HS structure and metabolic control mechanisms linking HS biosynthesis and expression with activity, less heterogeneous HS samples are required.…”