136316 20260218073552.0 doi 10.1002/anie.202405823 sideral 139156 ART-2024-139156 eng Redrado-Hernández, Sergio Broad protection against invasive fungal disease from a nanobody targeting the active site of fungal b-1,3-glucanosyltransferases 2024 Access copy available to the general public Unrestricted Invasive fungal disease accounts for ~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 insights about the role of b‐1,3‐glucan in fungal biology and demonstrate the potential of nanobodies in targeting fungal enzymes to combat invasive fungal diseases. info:eu-repo/semantics/openAccess All rights reserved http://www.europeana.eu/rights/rr-f/ 17.0 2024 CHEMISTRY, MULTIDISCIPLINARY 15 / 239 = 0.063 2024 Q1 T1 5.55 2024 Chemistry (miscellaneous) 2024 Q1 Catalysis 2024 Q1 27.6 2024 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion (orcid)0000-0001-6815-6720 Macías-León, Javier (orcid)0000-0002-5736-5452 Castro-López, Jorge Sanz, Ana Belén Dolader, Elena Universidad de Zaragoza (orcid)0000-0002-9730-2210 Arias, Maykel (orcid)0000-0002-5838-0857 González-Ramírez, Andrés Manuel Universidad de Zaragoza Sánchez-Navarro, David Petryk, Yuliya Farkaš, Vladimir Vincke, Cecile Muyldermans, Serge García-Barbazán, Irene Agua, Celia Universidad de Zaragoza Zaragoza, Óscar Arroyo, Javier (orcid)0000-0003-0154-0730 Pardo, Julián Universidad de Zaragoza Gálvez, Eva Universidad de Zaragoza (orcid)0000-0002-3122-9401 Hurtado-Guerrero, Ramón 1006 255 Universidad de Zaragoza Dpto. Fisiatría y Enfermería Área Enfermería 1011 566 Universidad de Zaragoza Dpto. Microb.Ped.Radio.Sal.Pú. Área Inmunología 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 1013 020 Universidad de Zaragoza Dpto. Cirugía Área Anatomía Patológica 63, 34 (2024), e202405823 [43 pp.] Angew. Chem. (Int. ed.) Angewandte Chemie (International ed.) 1433-7851 5865076 http://zaguan.unizar.es/record/136316/files/texto_completo.pdf Postprint info:eu-repo/date/embargoEnd/2025-07-22 1521305 http://zaguan.unizar.es/record/136316/files/texto_completo.jpg?subformat=icon icon Postprint info:eu-repo/date/embargoEnd/2025-07-22 oai:zaguan.unizar.es:136316 articulos driver 2026-02-17-20:32:28 ARTICLE