Biochemical and structural studies of target lectin SapL1 from the emerging opportunistic microfungus Scedosporium apiospermum

Abstract Scedosporium apiospermum is an emerging opportunistic fungal pathogen responsible for life-threatening infections in humans. Host–pathogen interactions often implicate lectins that have become therapeutic targets for the development of carbohydrate mimics for antiadhesive therapy. Here, we...

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Autores principales:	Dania Martínez-Alarcón, Viviane Balloy, Jean-Philippe Bouchara, Roland J. Pieters, Annabelle Varrot
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/eeac914cf9ca4ecdaad1df82d0cf84b1
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spelling	oai:doaj.org-article:eeac914cf9ca4ecdaad1df82d0cf84b12021-12-02T15:08:11ZBiochemical and structural studies of target lectin SapL1 from the emerging opportunistic microfungus Scedosporium apiospermum10.1038/s41598-021-95008-42045-2322https://doaj.org/article/eeac914cf9ca4ecdaad1df82d0cf84b12021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95008-4https://doaj.org/toc/2045-2322Abstract Scedosporium apiospermum is an emerging opportunistic fungal pathogen responsible for life-threatening infections in humans. Host–pathogen interactions often implicate lectins that have become therapeutic targets for the development of carbohydrate mimics for antiadhesive therapy. Here, we present the first report on the identification and characterization of a lectin from S. apiospermum named SapL1. SapL1 was found using bioinformatics as a homolog to the conidial surface lectin FleA from Aspergillus fumigatus known to play a role in the adhesion to host glycoconjugates present in human lung epithelium. In our strategy to obtain recombinant SapL1, we discovered the importance of osmolytes to achieve its expression in soluble form in bacteria. Analysis of glycan arrays indicates specificity for fucosylated oligosaccharides as expected. Submicromolar affinity was measured for fucose using isothermal titration calorimetry. We solved SapL1 crystal structure in complex with α-methyl-L-fucoside and analyzed its structural basis for fucose binding. We finally demonstrated that SapL1 binds to bronchial epithelial cells in a fucose-dependent manner. The information gathered here will contribute to the design and development of glycodrugs targeting SapL1.Dania Martínez-AlarcónViviane BalloyJean-Philippe BoucharaRoland J. PietersAnnabelle VarrotNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Dania Martínez-Alarcón Viviane Balloy Jean-Philippe Bouchara Roland J. Pieters Annabelle Varrot Biochemical and structural studies of target lectin SapL1 from the emerging opportunistic microfungus Scedosporium apiospermum
description	Abstract Scedosporium apiospermum is an emerging opportunistic fungal pathogen responsible for life-threatening infections in humans. Host–pathogen interactions often implicate lectins that have become therapeutic targets for the development of carbohydrate mimics for antiadhesive therapy. Here, we present the first report on the identification and characterization of a lectin from S. apiospermum named SapL1. SapL1 was found using bioinformatics as a homolog to the conidial surface lectin FleA from Aspergillus fumigatus known to play a role in the adhesion to host glycoconjugates present in human lung epithelium. In our strategy to obtain recombinant SapL1, we discovered the importance of osmolytes to achieve its expression in soluble form in bacteria. Analysis of glycan arrays indicates specificity for fucosylated oligosaccharides as expected. Submicromolar affinity was measured for fucose using isothermal titration calorimetry. We solved SapL1 crystal structure in complex with α-methyl-L-fucoside and analyzed its structural basis for fucose binding. We finally demonstrated that SapL1 binds to bronchial epithelial cells in a fucose-dependent manner. The information gathered here will contribute to the design and development of glycodrugs targeting SapL1.
format	article
author	Dania Martínez-Alarcón Viviane Balloy Jean-Philippe Bouchara Roland J. Pieters Annabelle Varrot
author_facet	Dania Martínez-Alarcón Viviane Balloy Jean-Philippe Bouchara Roland J. Pieters Annabelle Varrot
author_sort	Dania Martínez-Alarcón
title	Biochemical and structural studies of target lectin SapL1 from the emerging opportunistic microfungus Scedosporium apiospermum
title_short	Biochemical and structural studies of target lectin SapL1 from the emerging opportunistic microfungus Scedosporium apiospermum
title_full	Biochemical and structural studies of target lectin SapL1 from the emerging opportunistic microfungus Scedosporium apiospermum
title_fullStr	Biochemical and structural studies of target lectin SapL1 from the emerging opportunistic microfungus Scedosporium apiospermum
title_full_unstemmed	Biochemical and structural studies of target lectin SapL1 from the emerging opportunistic microfungus Scedosporium apiospermum
title_sort	biochemical and structural studies of target lectin sapl1 from the emerging opportunistic microfungus scedosporium apiospermum
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/eeac914cf9ca4ecdaad1df82d0cf84b1
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Biochemical and structural studies of target lectin SapL1 from the emerging opportunistic microfungus Scedosporium apiospermum

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