ResearcherscontroladhesionofE.colibacteria

Left:E.colibacteriacandockontothesaccharidemoleculesofthesyntheticglcocalyxusingtheFimHprotein.Right:Whenirradiatedwithlightatawavelengthof365nanometres,thesaccharidemoleculesonthesurfacebendawayandcannotberecognisedbytheproteins.Thebacteriacanthennolongerdockontothehostcell.
Figure/Copyright:Wiley-VCHVerlagGmbH&Co.KGaA.Reproducedwithpermission.

AresearchteamfromKielUniversity(CAU)andGoetheUniversityFrankfurthavejointlycreatedasyntheticsurfaceonwhichtheadhesionofE.colibacteriacanbecontrolled.Thelayer,whichisonlyapproximatelyfournanometresthick,imitatesthesaccharidecoating(glycocalyx)ofcellsontowhichthebacteriaadheresuchasduringaninfection.Thisdockingprocesscanbeswitchedonandoffusinglight.Thismeansthatthescientistshavenowmadeanimportantsteptowardsunderstandingtherelationshipbetweensugar(carbohydrates)andbacterialinfections.TheirresearchresultsembellishthefrontpageofthelatestissueoftherenownedjournalAngewandteChemie(AppliedChemistry).

Thebondbetweeneithercellsandothercellsorcellsandsurfacesisvitaltoorganisms,forexampleinthedevelopmentofinternalorgansandtissue.However,thesemechanismsarealsoinvolvedinillnessandinfections.TheE.colibacteriausedintheexperimentcancauseurinarytractinfections,meningitis,sepsisandothersevereillnesses.Inordertounderstandandtreattheseillnesses,researchersneedtodecipherthemolecularprocesseswhichallowthebacteriacellstodockontothehealthyhostcells.

Thisoftenhappensbywayofproteins,whichinteractwithcarbohydratestructuresonthesurfaceofthehostcellbymeansofacomplexfitprinciple(simplified:lock-and-keyprinciple).TheKiel/Frankfurtstudydemonstratesforthefirsttimethatthespatialorientationofthecarbohydratestructuresiscrucialtothisprocess.However,innaturalglycocalyx,amerenanometrethickpolysaccharidelayercoveringallcells,therelationshipsarestilltoocomplextouncoverhowproteinsandcarbohydratesidentifyeachother.

InCollaborativeResearchCenter(SFB)677'FunctionbySwitching',ProfessorThisbeK.Lindhorst,chemistatKielUniversity,andherteamconstructmoleculeswhich,whenirradiatedbylightatdifferentwavelengths,operateasbiologicalswitches.TogetherwiththeworkinggrouparoundthesurfacesspecialistProfessorAndreasTerfort(FrankfurtUniversity),theLindhorstgrouphasnowproducedasystemwithwhichtheorientationofthesaccharidedockingpoints,andthusthebondingofE.colibacteria,canbecontrolled.Todothis,thescientistscoveredanextremelythingoldsurfacewithapreciselydefinedsaccharidecovering,coupledtoazobenzene.Thisisahydrocarboncontaininganitrogenbridgeandoperatingasahingecontrolledbylight.Thebondingpropertiesofthesaccharidecoatingcannowbeswitchedusingthismethod:iftheresearchersirradiatetheirsystemwithlightwithawavelengthof365nanometres,considerablyfewerpathogenicbacteriacellscanadheretothesyntheticsurface.Thesaccharidemoleculesturnawayfromthebacteria,inasense,andcannolongerberecognised.Whenswitchedonby450nanometrewavelengthlightwaves,ontheotherhand,thestructuresreorientatesuchthatthebacteriacellscandockononceagain.Inthisway,E.coliadhesioncanbecontrolled.

"Byemployingalayersystemonasolidsurface,incombinationwithaphoto-hinge,thecomplexdynamicsofarealglycocalyxcanbereducedtotheprincipalprocessesandthusbebetterunderstood",explainsTerfort."Itshouldbepossibletotransferthisnovelapproachtootherbiologicalboundarylayersystems."

"Basedonourmodelsystem,glycocalyxrecognitionandbondingeffectscanbepreciselydefinedandinvestigatedfromacompletelynewangle",saysLindhorst."Ifwecanlearnhowtoinfluenceglycocalyxinthecontextoftherelationshipbetweenhealthandhealing,itwillleadtoarevolutioninmedicinalchemistry."

Originalpublication

Switchingofbacterialadhesiontoaglycosylatedsurfacebyreversiblereorientationofthecarbohydrateligand.TheresaWeber,VijayanandChandrasekaran,InsaStamer,MikkelB.Thygesen,AndreasTerfortandThisbeK.Lindhorst.Angew.Chem.48/2014DOI:10.1002/ange.201409808and10.1002/anie.201409808(Angew.Chem.Int.Ed.)

Contact

Prof.DrThisbeK.Lindhorst

Christian-Albrechts-UniversittzuKiel

OttoDiels-InstitutfrOrganischeChemie

Tel.:+49(0)431880-2023

E-mail:tklind@oc.uni-kiel.de

Prof.DrAndreasTerfort

Goethe-UniversittFrankfurt

Tel.:+49(0)69798-29180.

E-mail:aterfort@chemie.uni-frankfurt.de