Identification of regulatory network topological u

BioMedCentralPage1of18(pagenumbernotforcitationpurposes)BMCMicrobiologyOpenAccessResearcharticleIdentificationofregulatorynetworktopologicalunitscoordinatingthegenome-widetranscriptionalresponsetoglucoseinEscherichiacoliRosaMaríaGutierrez-Ríos1,JulioAFreyre-Gonzalez3,OsbaldoResendis3,JulioCollado-Vides3,MiltonSaier4andGuillermoGosset*2Address:1DepartamentosdeMicrobiologíaMolecular,InstitutodeBiotecnología,UniversidadNacionalAutónomadeMéxico,Apdo.Postal510-3,Cuernavaca,Morelos62250,México,2IngenieríaCelularyBiocatálisis,InstitutodeBiotecnología,UniversidadNacionalAutónomadeMéxico,Apdo.Postal510-3,Cuernavaca,Morelos62250,México,3ProgramadeGenómicaComputacional,CentrodeCienciasGenómicas,UniversidadNacionalAutónomadeMéxicoand4DivisionofBiologicalSciences,UniversityofCaliforniaatSanDiego,LaJolla,CA,92093-0116,USAEmail:RosaMaríaGutierrez-Rí[e-mail];[e-mail];[e-mail];[e-mail];[e-mail];GuillermoGosset*[e-mail]*CorrespondingauthorAbstractBackground:GlucoseisthepreferredcarbonandenergysourceforEscherichiacoli.Acomplexregulatorynetworkcoordinatesgeneexpression,transportandenzymeactivitiesinresponsetothepresenceofthissugar.Todeterminetheextentofthecellularresponsetoglucose,weappliedanapproachcombiningglobaltranscriptomeandregulatorynetworkanalyses.Results:Transcriptomedatafromisogenicwildtypeandcrp-strainsgrowninLuria-Bertanimedium(LB)orLB+4g/Lglucose(LB+G)wereanalyzedtoidentifydifferentiallytranscribedgenes.Wedetected180and200genesdisplayingincreasedandreducedrelativetranscriptlevelsinthepresenceofglucose,respectively.TheobservedexpressionpatterninLBwasconsistentwithagluconeogenicmetabolicstateincludingactivetransportandinterconversionofsmallmoleculesandmacromolecules,inductionofprotease-encodinggenesandapartialheatshockresponse.InLB+G,catabolicrepressionwasdetectedfortransportandmetabolicinterconversionactivities.Wealsodetectedanincreasedcapacityfordenovosynthesisofnucleotides,aminoacidsandproteins.ClusteranalysisofasubsetofgenesrevealedthatCRPmediatescataboliterepressionformostofthegenesdisplayingreducedtranscriptlevelsinLB+G,whereasFisparticipatesintheupregulationofgenesunderthiscondition.Ananalysisoftheregulatorynetwork,intermsoftopologicalfunctionalunits,revealed8interconnectedmoduleswhichagainexposedtheimportanceofFisandCRPasdirectlyresponsibleforthecoordinatedresponseofthecell.ThiseffectwasalsoseenwithothernotextensivelyconnectedtranscriptionfactorssuchasFruRandPdhR,whichshowedaconsistentresponseconsideringmediacomposition.Conclusion:ThisworkallowedtheidentificationofeightinterconnectedregulatorynetworkmodulesthatincludesCRP,Fisandothertranscriptionalfactorsthatresponddirectlyorindirectlytothepresenceofglucose.Inmostcases,eachofthesemodulesincludesgenesencodingphysiologicallyrelatedfunctions,thusindicatingaconnectionbetweenregulatorynetworktopologyandrelatedcellularfunctionsinvolvedinnutrientsensingandmetabolism.Published:8June2007BMCMicrobiology2007,7:53doi:10.1186/1471-2180-7-53Received:15January2007Accepted:8June2007Thisarticleisavailablefrom:©2007Gutierrez-Ríosetal;licenseeBioMedCentralLtd.ThisisanOpenAccessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense(),whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.BMCMicrobiology2007,7:53(pagenumbernotforcitationpurposes)BackgroundIntheirnaturalenvironments,bacteriamustadapttochangingphysicochemicalconditions.Adaptationresponsesarecontrolledbyacomplexnetworkofsensoryandregulatoryproteinsthatmodulatecellularfunctionsatthetranscriptionalandposttranscriptionallevels.Nutrientavailability,rangingfromsufficiencytototaldeprivation,isoneoftheenvironmentalvariablesthecellisconstantlysensing.Amongnutrients,carbohydratesareparticularlyimportanttothecellsincetheyareutilizedasbothcarbonandenergysources.Glucoseisthemostabundantaldoseinnature,beingpresentmostlyinpoly-mericstatesasstarchandcellulose[1].Thissugaristhepreferredcarbonandenergysourceforthegram-negativebacteriumEscherichiacoli(E.coli)[2].SpecializedproteinsystemsarepresentinE.colitosense,selectandtransportglucose.Thissugarisinternalizedandphosphorylatedbythephosphoenolpyruvate:sugarphosphotransferasesys-tem(PTS).Thissystemcatalyzesgrouptranslocation,aprocessthatcouplestransportofsugarstotheirphsospho-rylation.ThePTSiswidespreadinbacteriabutabsentinArchaeaandeukaryoticorganisms[3,4].Itiscomposedofsolublenonsugar-specificproteincomponents,EnzymeI(EI)andthephosphohistidinecarrierprotein(HPr)whichrelayaphosphorylgroupfromtheglycolyticinter-mediate,phosphoenolpyruvate(PEP),toanyofthediffer-entsugar-specificenzymeIIcomplexes.GlucoseisimportedbytheIIGlccomplex,composedofthesolubleIIAGlcenzymeandtheintegralmembranepermeaseIICB-Glc[5].ThepreferrednutritionalstatusofglucoseforE.c