2026-05-22T23:05:30Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/250912025-12-18T12:59:58Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19609col_20.500.12105_16973
Repisalud
author
Redrado-Hernández, Sergio
author
Macías-León, Javier
author
Castro-López, Jorge
author
Belén Sanz, Ana
author
Dolader, Elena
author
Arias, Maykel
author
González-Ramírez, Andrés Manuel
author
Sánchez-Navarro, David
author
Petryk, Yuliya
author
Farkaš, Vladimír
author
Vincke, Cécile
author
Muyldermans, Serge
author
Garcia-Barbazan, Irene
author
Del Agua, Celia
author
Zaragoza, Oscar
author
Arroyo, Javier
author
Pardo, Julián
author
Gálvez, Eva M
author
Hurtado-Guerrero, Ramon
author
Redrado-Hernández, Sergio
author
Macías-León, Javier
author
Castro-López, Jorge
author
Belén Sanz, Ana
author
Dolader, Elena
author
Arias, Maykel
author
González-Ramírez, Andrés Manuel
author
Sánchez-Navarro, David
author
Petryk, Yuliya
author
Farkaš, Vladimír
author
Vincke, Cécile
author
Muyldermans, Serge
author
Del Agua, Celia
author
Zaragoza, Oscar
author
Arroyo, Javier
author
Pardo, Julián
author
Gálvez, Eva M
author
Hurtado-Guerrero, Ramon
funder
Fundación Agencia Aragonesa para la Investigación y el Desarrollo
funder
Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)
funder
Instituto de Salud Carlos III
funder
Ministry of Education, Youth and Sports (República Checa)
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Comunidad de Madrid (España)
funder
Asociación de Padres de Niños Oncológicos de Aragón
funder
Gobierno de Aragón (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Unión Europea. Comisión Europea. 7 Programa Marco
funder
Ministerio de Ciencia e Innovación (España)
funder
Agencia Estatal de Investigación (España)
2024-10-11T11:16:18Z
2024-10-11T11:16:18Z
2024-08-19
Angew Chem Int Ed Engl. 2024 Aug 19;63(34):e202405823.
1521-3773
1433-785110.1002/anie.202405823
Angewandte Chemie
38856634
https://hdl.handle.net/20.500.12105/25091
Invasive fungal disease accounts for about 3.8 million deaths annually, an unacceptable rate that urgently prompts the discovery of new knowledge-driven treatments. We report the use of camelid single-domain nanobodies (Nbs) against fungal β-1,3-glucanosyltransferases (Gel) involved in β-1,3-glucan transglycosylation. Crystal structures of two Nbs with Gel4 from Aspergillus fumigatus revealed binding to a dissimilar CBM43 domain and a highly conserved catalytic domain across fungal species, respectively. Anti-Gel4 active site Nb3 showed significant antifungal efficacy in vitro and in vivo prophylactically and therapeutically against different A. fumigatus and Cryptococcus neoformans isolates, reducing the fungal burden and disease severity, thus significantly improving immunocompromised animal survival. Notably, C. deneoformans (serotype D) strains were more susceptible to Nb3 and genetic Gel deletion than C. neoformans (serotype A) strains, indicating a key role for β-1,3-glucan remodelling in C. deneoformans survival. These findings add new insight about the role of β-1,3-glucan in fungal biology and demonstrate the potential of nanobodies in targeting fungal enzymes to combat invasive fungal diseases.
eng
Glucanosyltransferases
Cell wall
Invasive fungal infections
Nanobodies
Transglycosylases
Broad Protection against Invasive Fungal Disease from a Nanobody Targeting the Active Site of Fungal β-1,3-Glucanosyltransferases
research article
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BroadProtectionAgainstInvasiveFungalDisease_2024.pdf.txt
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