At a Supra-Physiological Concentration, Human Sexual Hormones Act as Quorum-Sensing Inhibitors.docVIP

AtaSupra-PhysiologicalConcentration,HumanSexual HormonesActasQuorum-SensingInhibitors Ame′lieBeury-Cirou1,2,Me′lanieTannie`res1,CorinneMinard3,LaurentSoule`re4,TsiryRasamiravaka5, RobertH.Dodd3,YvesQueneau4,YvesDessaux1,CatherineGuillou3,OlivierM.Vandeputte5*, DenisFaure1* 1Institut des Sciences du Ve′ge′tal (ISV) UPR 2355, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France, 2Seeds Innovation Protection Research and Environment(SIPRE),Comite′NordPlantsdePommesdeTerre(CNPPT),Achicourt,France,3InstitutdeChimiedesSubstancesNaturelles(ICSN)UPR2301,CentreNational delaRechercheScientifique,Gif-sur-Yvette,France,4InstitutdeChimieetBiochimieMole′culaires etSupramole′culaires(ICBMS)UMR5246,INSALyon-Universite′ Lyon1, Villeurbanne,France,5LaboratoiredeBiotechnologieVe′ge′tale,Universite′ LibredeBruxelles,Gosselies,Belgium Abstract N-Acylhomoserine lactone (AHL)-mediated quorum-sensing (QS) regulates virulence functions in plant and animal pathogenssuchasAgrobacteriumtumefaciensandPseudomonasaeruginosa.Achemolibraryofmorethan3500compounds was screened using two bacterial AHL-biosensors to identify QS-inhibitors (QSIs). The purity and structure of 15 QSIs selectedthroughthisscreeningwereverifiedusingHPLCMS/MStoolsandtheiractivitytestedontheA.tumefaciensandP. aeruginosabacterialmodels.TheIC50valueoftheidentifiedQSIsrangedfrom2.5to90mg/ml,valuesthatareinthesame rangeasthosereportedforthepreviouslyidentifiedQSI4-nitropyridine-N-oxide(IC5024mg/ml).Underthetestedculture conditions,mostoftheidentifiedQSIsdidnotexhibitbacteriostaticorbactericidalactivities.OnethirdofthetestedQSIs, including the plant compound hordenine and the human sexual hormone estrone, decreased the frequency of the QS- regulatedhorizontaltransferofthetumor-inducing(Ti)plasmidinA.tumefaciens.Hordenine,estroneaswellasitsstructural relativesestriolandestradiol,alsodecreasedAHLaccumulationandtheexpressionofsixQS-regulatedgenes(lasI,lasR,lasB, rhlI, rhlR, and rhlA) in cultures of the op