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

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Hall, Amy R., Blakeman, Jamie T., Eissa, Ahmed M., Chapman, Paul , Morales-García, Ana L., Stennett, Laura, Martin, Oihane, Giraud, Emilie, Dockrell, David H., Cameron, Neil R., Wiese, Martin, Yakob, Laith, Rogers, Matthew E. and Geoghegan, Mark (2020) Glycan–glycan interactions determine Leishmania attachment to the midgut of permissive sand fly vectors. Chemical Science, 11 (40). pp. 10973-10983. doi:10.1039/d0sc03298k

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Official URL: http://dx.doi.org/10.1039/d0sc03298k

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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.

Item Type: Journal Article
Subjects: Q Science > QP Physiology
R Medicine > RA Public aspects of medicine
R Medicine > RC Internal medicine
Divisions: Faculty of Science > Chemistry
Library of Congress Subject Headings (LCSH): Leishmaniasis, Proteins -- Metabolism, Glycomics
Journal or Publication Title: Chemical Science
Publisher: Royal Society of Chemistry
ISSN: 2041-6520
Official Date: 3 September 2020
Dates:
DateEvent
3 September 2020Published
2 September 2020Accepted
Date of first compliant deposit: 16 November 2020
Volume: 11
Number: 40
Page Range: pp. 10973-10983
DOI: 10.1039/d0sc03298k
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
BB/H022406/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
MR/R005850/1[MRC] Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
Fellowship BF109.183País Vasco (Spain)http://viaf.org/viaf/123204011
F/00128/BOLeverhulme Trusthttp://dx.doi.org/10.13039/501100000275
EP/I012060/1[EPSRC] Engineering and Physical Sciences Research Councilhttp://dx.doi.org/10.13039/501100000266
Doctoral studentshipConsejo Nacional de Ciencia y Tecnologíahttp://dx.doi.org/10.13039/501100003141
Doctoral training grant[EPSRC] Engineering and Physical Sciences Research Councilhttp://dx.doi.org/10.13039/501100000266
iCASE award[EPSRC] Engineering and Physical Sciences Research Councilhttp://dx.doi.org/10.13039/501100000266

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