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dc.rights.licenseopenen_US
dc.contributor.authorDJENONTIN, Elie
hal.structure.identifierCentre Hospitalier Régional Universitaire de Nancy [CHRU Nancy]
dc.contributor.authorDEBOURGOGNE, Anne
hal.structure.identifierDynamic Microbiology - EA 7380 [DYNAMIC]
hal.structure.identifierMazandaran University of Medical Sciences
dc.contributor.authorMOUSAVI, Bita
hal.structure.identifierUniversité de Bordeaux [UB]
hal.structure.identifierCHU de Bordeaux Pellegrin [Bordeaux]
hal.structure.identifierCentre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] [CRCTB]
dc.contributor.authorDELHAES, Laurence
hal.structure.identifierCentre Hospitalier Universitaire [CHU Grenoble] [CHUGA]
hal.structure.identifierTranslational microbial Evolution and Engineering [TIMC-TrEE]
hal.structure.identifierTranslational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 [TIMC]
hal.structure.identifierUniversité Grenoble Alpes [UGA]
dc.contributor.authorCORNET, Muriel
hal.structure.identifierDynamic Microbiology - EA 7380 [DYNAMIC]
dc.contributor.authorVALSECCHI, Isabel
dc.contributor.authorADEBO, Makiath
hal.structure.identifierÉcole nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique [ONIRIS]
dc.contributor.authorGUILLOT, Jacques
hal.structure.identifierHôpital Henri Mondor
dc.contributor.authorBOTTEREL, Françoise
hal.structure.identifierUnité de Parasitologie-Mycologie, Service de Microbiologie [Hôpital Necker-Enfants-Malades, Paris]
dc.contributor.authorDANNAOUI, Eric
dc.date.accessioned2025-06-16T11:55:04Z
dc.date.available2025-06-16T11:55:04Z
dc.date.issued2024-07-15
dc.identifier.issn0933-7407en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/206920
dc.description.abstractEnAbstract Background The resistance of Aspergillus flavus to the azole antifungal drugs is an emerging problem. Mutations in the molecular targets of the azole antifungals ‐ CYP 51 A, B and C ‐ are possible mechanisms of resistance, but data to confirm this hypothesis are scarce. In addition, the behaviour of resistant strains in vitro and in vivo is not yet understood. Objectives This study had 3 objectives. The first was to compare the sequences of CYP51 A, B and C in resistant and susceptible strains of A. flavus . The second was to look for the existence of a fitness cost associated with resistance. The third was to evaluate the activity of voriconazole and posaconazole on resistant strains in the Galleria mellonella model. Methods The CYP51 A, B and C sequences of seven resistant strains with those of four susceptible strains are compared. Fitness costs were assessed by growing the strains in RPMI medium and testing their virulence in G. mellonella larvae. In addition, G. mellonella larvae infected with strains of A. flavus were treated with voriconazole and posaconazole. Results In the CYP51A sequences, we found the A91T, C708T and A1296T nucleotide substitutions only in the resistant strains. The resistant strains showed a fitness cost with reduced in vitro growth and reduced virulence in G. mellonella . In vivo resistance to posaconazole is confirmed in a strain with the highest MIC for this antifungal agent. Conclusions These results allow to conclude that some substitutions in CYP51 genes, in particular CYP51A , contribute to resistance to azole drugs in A. flavus . The study of the relationship between drug dosage and treatment duration with resistance and the reduction of fitness costs in resistant strains is a major perspective of this study. This work could help to establish recommendations for the treatment of infections with resistant strains of A. flavus.
dc.language.isoENen_US
dc.title.enAzole resistance in Aspergillus flavus and associated fitness cost
dc.typeArticle de revueen_US
dc.identifier.doi10.1111/myc.13766en_US
dc.subject.halSciences du Vivant [q-bio]/Biotechnologiesen_US
bordeaux.journalMycosesen_US
bordeaux.page2169en_US
bordeaux.volume67en_US
bordeaux.hal.laboratoriesCentre de Recherche Cardio-Thoracique de Bordeaux (CRCTB) - U1045en_US
bordeaux.issue7en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcehal
hal.identifierhal-04997696
hal.version1
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
workflow.import.sourcehal
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Mycoses&rft.date=2024-07-15&rft.volume=67&rft.issue=7&rft.spage=2169&rft.epage=2169&rft.eissn=0933-7407&rft.issn=0933-7407&rft.au=DJENONTIN,%20Elie&DEBOURGOGNE,%20Anne&MOUSAVI,%20Bita&DELHAES,%20Laurence&CORNET,%20Muriel&rft.genre=article


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