Antifungal Efficacy during Candida krusei Infection in Non-Conventional Models Correlates with the Yeast In Vitro Susceptibility Profile.docVIP

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Antifungal Efficacy during Candida krusei Infection in Non-Conventional Models Correlates with the Yeast In Vitro Susceptibility Profile.doc

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Antifungal Efficacy during Candida krusei Infection in Non-Conventional Models Correlates with the Yeast In Vitro Susceptibility Profile

AntifungalEfficacyduringCandidakruseiInfectionin Non-ConventionalModelsCorrelateswiththeYeastIn VitroSusceptibilityProfile LilianaScorzoni1,2,MariaPilardeLucas3,AnaCeciliaMesa-Arango1,4,AnaMarisaFusco-Almeida2, Encarnacio′nLozano3,ManuelCuenca-Estrella1,MariaJoseMendes-Giannini2*,OscarZaragoza1* 1MycologyReferenceLaboratory,NationalCentreforMicrobiology,InstitutodeSaludCarlosIII,Madrid,Spain,2Laborato′riodeMicologiaCl?′nica,FaculdadedeCie?ncias Farmace?uticas, Universidade Estadual Paulista de Sa?o Paulo, Araraquara, Brazil, 3Department of Cellular Biology, National Centre for Microbiology, Instituto de Salud CarlosIII,Madrid,Spain,4GroupofInvestigativeDermatology,UniversityofAntioquia,Medell?′n,Colombia Abstract The incidence of opportunistic fungal infections has increased in recent decades due to the growing proportion of immunocompromised patients in our society. Candida krusei has been described as a causative agent of disseminated fungalinfectionsinsusceptiblepatients.Althoughitsprevalenceremainslowamongyeastinfections(2–5%),itsintrinsic resistancetofluconazolemakesthisyeastimportantfromepidemiologicaspects.Nonmammalianorganismsarefeasible modelstostudyfungalvirulenceanddrugefficacy.InthisworkwehaveusedthelepidopteranGalleriamellonellaandthe nematodeCaenorhabditiselegansasmodelstoassessantifungalefficacyduringinfectionbyC.krusei.ThisyeastkilledG. mellonella at 25, 30 and 37uC and reduced haemocytic density. Infected larvae melanized in a dose-dependent manner. FluconazoledidnotprotectagainstC.kruseiinfection,incontrasttoamphotericinB,voriconazoleorcaspofungin.However, thedosesoftheseantifungalsrequiredtoobtainlarvaeprotectionwerealwayshigherduringC.kruseiinfectionthanduring C.albicansinfection.SimilarresultswerefoundinthemodelhostC.elegans.Ourworkdemonstratesthatnonmammalian modelsareusefultoolstoinvestigateinvivoantifungalefficacyandvirulenceofC.krusei. Citation: Scorzoni L, de Lucas MP, Mesa-Arango AC, Fusco-Almeida AM, Lozano E, et al. (2013) Antifungal E