000136316 001__ 136316
000136316 005__ 20240829112947.0
000136316 0247_ $$2doi$$a10.1002/anie.202405823
000136316 0248_ $$2sideral$$a139156
000136316 037__ $$aART-2024-139156
000136316 041__ $$aeng
000136316 100__ $$aRedrado-Hernández, Sergio
000136316 245__ $$aBroad protection against invasive fungal disease from a nanobody targeting the active site of fungal b-1,3-glucanosyltransferases
000136316 260__ $$c2024
000136316 5060_ $$aAccess copy available to the general public$$fUnrestricted
000136316 5203_ $$aInvasive 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.
000136316 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000136316 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000136316 700__ $$0(orcid)0000-0001-6815-6720$$aMacías-León, Javier
000136316 700__ $$0(orcid)0000-0002-5736-5452$$aCastro-López, Jorge
000136316 700__ $$aSanz, Ana Belén
000136316 700__ $$aDolader, Elena$$uUniversidad de Zaragoza
000136316 700__ $$0(orcid)0000-0002-9730-2210$$aArias, Maykel
000136316 700__ $$0(orcid)0000-0002-5838-0857$$aGonzález-Ramírez, Andrés Manuel$$uUniversidad de Zaragoza
000136316 700__ $$aSánchez-Navarro, David
000136316 700__ $$aPetryk, Yuliya
000136316 700__ $$aFarkaš, Vladimir
000136316 700__ $$aVincke, Cecile
000136316 700__ $$aMuyldermans, Serge
000136316 700__ $$aGarcía-Barbazán, Irene
000136316 700__ $$aAgua, Celia$$uUniversidad de Zaragoza
000136316 700__ $$aZaragoza, Óscar
000136316 700__ $$aArroyo, Javier
000136316 700__ $$0(orcid)0000-0003-0154-0730$$aPardo, Julián$$uUniversidad de Zaragoza
000136316 700__ $$aGálvez, Eva$$uUniversidad de Zaragoza
000136316 700__ $$0(orcid)0000-0002-3122-9401$$aHurtado-Guerrero, Ramón
000136316 7102_ $$11006$$2255$$aUniversidad de Zaragoza$$bDpto. Fisiatría y Enfermería$$cÁrea Enfermería
000136316 7102_ $$11011$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Inmunología
000136316 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000136316 7102_ $$11013$$2020$$aUniversidad de Zaragoza$$bDpto. Cirugía$$cÁrea Anatomía Patológica
000136316 773__ $$g63, 34 (2024), e202405823 [43 pp.]$$pAngew. Chem. (Int. ed.)$$tAngewandte Chemie (International ed.)$$x1433-7851
000136316 8564_ $$s5865076$$uhttps://zaguan.unizar.es/record/136316/files/texto_completo.pdf$$yPostprint$$zinfo:eu-repo/date/embargoEnd/2025-07-22
000136316 8564_ $$s1521305$$uhttps://zaguan.unizar.es/record/136316/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint$$zinfo:eu-repo/date/embargoEnd/2025-07-22
000136316 909CO $$ooai:zaguan.unizar.es:136316$$particulos$$pdriver
000136316 951__ $$a2024-08-29-11:26:06
000136316 980__ $$aARTICLE