Small Molecule Inhibitors of the Candida albicans Budded-to-Hyphal Transition Act through Multiple Signaling Pathways 英文参考文献.docVIP

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Small Molecule Inhibitors of the Candida albicans Budded-to-Hyphal Transition Act through Multiple Signaling Pathways 英文参考文献.doc

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Small Molecule Inhibitors of the Candida albicans Budded-to-Hyphal Transition Act through Multiple Signaling Pathways 英文参考文献

SmallMoleculeInhibitorsoftheCandidaalbicans Budded-to-HyphalTransitionActthroughMultiple SignalingPathways JohnMidkiff,NathanBorochoff-Porte,DylanWhite,DouglasI.Johnson* DepartmentofMicrobiologyandMolecularGenetics,UniversityofVermont,Burlington,Vermont,UnitedStatesofAmerica Abstract The ability of the pathogenic yeast Candida albicans to interconvert between budded and hyphal growth states, herein termedthebudded-to-hyphaltransition(BHT),isimportantforC.albicansdevelopmentandvirulence.TheBHTisunderthe controlofmultiplecellsignalingpathwaysthatrespondtoexternalstimuli,includingnutrientavailability,hightemperature, andpH.Previousstudiesidentified21smallmoleculesthatcouldinhibittheC.albicansBHTinresponsetocarbonlimitation inSpidermedia.However,thestudieshereinshowthattheBHTinhibitorshadvaryingefficaciesinotherhyphal-inducing media,reflectingtheirvaryingabilitiestoblocksignalingpathwaysassociatedwiththedifferentmedia.Chemicalepistasis analyses suggest that most, but not all, of the BHT inhibitors were acting through either the Efg1 or Cph1 signaling pathways.Notably,theBHTinhibitorclozapine,aFDA-approveddrugusedtotreatatypicalschizophreniabyinhibitingG- protein-coupleddopaminereceptorsinthebrain,andseveralofitsfunctionalanalogswereshowntoactatthelevelofthe Gpr1 G-protein-coupled receptor. These studies are the first step in determining the target and mechanism of action of theseBHTinhibitors,whichmayhavetherapeuticanti-fungalutilityinthefuture. Citation:MidkiffJ,Borochoff-PorteN,WhiteD,JohnsonDI(2011)SmallMoleculeInhibitorsoftheCandidaalbicansBudded-to-HyphalTransitionActthrough MultipleSignalingPathways.PLoSONE6(9):e25395.doi:10.1371/journal.pone.0025395 Editor:DanaDavis,UniversityofMinnesota,UnitedStatesofAmerica ReceivedJuly12,2011;AcceptedSeptember2,2011;PublishedSeptember26,2011 Copyright: ? 2011 Midkiff et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andrep