Identification of the glycan binding profile of human and rodent Plasmodium sporozoites

Journal Publication ResearchOnline@JCU
Poole, Jessica;Hartley-Tassell, Lauren E.;Day, Christopher J.;Stanisic, Danielle I.;Groves, Penny L.;Chakravarty, Sumana;Lee Sim, B. Kim;Hoffman, Stephen L.;Tiralongo, Joe;Bovin, Nicolai;Doolan, Denise L.;Jennings, Michael P.
Abstract

The transmission of Plasmodium spp. sporozoites to the mammalian host is the first step in the initiation of the mosquito-borne disease known as malaria. The exact route of transmission from the bloodstream to the liver is still not clearly elucidated, and identification of the host glycan structures bound by the sporozoites may inform as to which host cells are involved. Here, we provide a comprehensive analysis of the glycan structures that sporozoites from the human pathogen, P. falciparum, and the rodent pathogen, P. yoelii, recognize and bind. Glycan array analysis was used to profile the glycans bound by the sporozoites, and the binding affinities of these sporozoite-glycan interactions were then determined by surface plasmon resonance. Data showed that the different Plasmodium spp. bind different classes of glycans. P. falciparum was observed to bind to glycans with terminal N-acetylgalactosamine (GalNAc) or Galactose (Gal) linked to a GalNAc, and the highest-affinity observed was with the GalNAc monosaccharide (12.5 nM). P. yoelii bound glycosaminoglycans, mannosyl glycans, Gal linked to N-acetylglucosamine structures, and the αGal epitope. The highest-affinity interaction for P. yoelii was with the αGal epitope (31.4 nM). This is the first study to identify the key host glycan structures recognized by human and rodent Plasmodium spp. sporozoites. An understanding of how Plasmodium sporozoites interact with the specific glycan structures identified here may provide further insight into this infectious disease that could help direct the design of an effective therapeutic.

Journal

ACS Infectious Diseases

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7

ISBN/ISSN

2373-8227

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Issue

8

Pages Count

7

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Publisher

American Chemical Society

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DOI

10.1021/acsinfecdis.1c00084