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Glycan-glycan interactions determine Leishmania attachment to the midgut of permissive sand fly vectors

Lookup NU author(s): Professor Mark GeogheganORCiD

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Abstract

Direct glycan–glycan interactions are increasingly implicated in survival and pathogenicity of bacteria. Here, we show that they can be exploited by protozoan parasites in their insect hosts. Force spectroscopy revealed that Leishmania promastigotes display a high-affinity biomolecular interaction between their lipophosphoglycan glycocalyx and mimics of N-acetyl-D-galactosamine, commonly expressed on the midguts of a wide range of sand fly vector species. This enabled gut-adhesive nectomonad promastigotes of Leishmania mexicana to efficiently bind to membrane-bound mucin-like, O-linked glycoproteins of the sand fly Lutzomyia longipalpis, an event crucial for parasite survival, and accounts for a permissive mode of binding. Thus, direct interaction between parasite and sand fly midgut glycans are key to permitting vector competence for all forms of leishmaniasis worldwide. In addition, these studies demonstrate the feasibility of interfering with these interactions as transmission-blocking vaccines.

Publication metadata

Author(s): Hall AR, Blakeman JT, Eissa AM, Chapman P, Morales-García AL, Stennett L, Martin O, Giraud E, Dockrell DH, Cameron NR, Wiese M, Yakob Y, Rogers ME, Geoghegan M

Publication type: Article

Publication status: Published

Journal: Chemical Science

Year: 2020

Volume: 11

Issue: 40

Pages: 10973-10983

Print publication date: 28/10/2020

Online publication date: 03/09/2020

Acceptance date: 02/09/2020

Date deposited: 21/10/2020

ISSN (print): 2041-6520

ISSN (electronic): 2041-6539

Publisher: Royal Society of Chemistry

URL: https://doi.org/10.1039/d0sc03298k

DOI: 10.1039/d0sc03298k

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