Plasticity and Redundancy in Proteins Important for Toxoplasma Invasion.
2015
Phenotypic plasticity encompasses theversatile abilitiesofanorganismtomodify itspheno-typeaccording tochanges intheenvironment. Such adaptations, inresponse toadecreaseoffitness, arecommonlyexploited bymicroorganismsand plantsthat cannoteasilyescape theirenvironment and,hence, areatriskofextinction. Functionalredundancy and plasticity isthereforeanticipatedforobligateintracellularparasites,includingmembersofthephylumApi-complexa, toensure successful hostcellinvasion—acritical stepfortheirsurvival.Thephylum Apicomplexaincludes manymedically and veterinary-relevantparasites, mostnotablythehuman pathogens Plasmodium and Toxoplasma gondii,responsible formalariaandtoxoplasmosis, respectively. Theseparasites arethe moststudied ofthephylum, notonlybecauseoftheirprevalence butalsobecauseoftheiraccessibility togeneticmanipulation [1,2],whichhasallowedthe investigation ofseveral aspects oftheirlyticcycle,particularly theirmechanisms ofentryintothe targetcell.InvasionbymostApicomplexais amultistep process consisting ofrecognition,attachment,andactivepenetration intohostcells,which hasbeendissected in depthinToxoplasma tachy-zoites [3].Parasite propulsionintothe hostcellis powered byamyosinmotor complextermedtheglideosome.During motilityandinvasion,T.gondii myosinA (TgMyoA)presumablytranslocates adhesins atthe moving junction(MJ)fromtheapicaltotheposterior poleoftheparasite [4].TheMJforms aconstriction aroundthe parasiteatthepointofentry intothehostcellthat appearsasaring structure. Apicalmembrane antigen 1(AMA1)in association withacomplexofrhoptry neckproteins (RONs) that areanchored intothehostcorticalcytoskeleton[5]arethecurrently knowncomponentsofthisMJ.Insultsimposed upon theparasitebyexperimentalgenomeediting strategies, suchasabla-tionofTgMyoAand TgAMA1 genes,significantlycompromisedthe fitnessoftheparasitesandhavenowbeendemonstratedtoelicitphenotypic plasticity. Such plasticityhas uncoveredinformative redundancy and adaptationmechanisms.Hereafter, wecompare and contrast themethodologies availabletoinvestigatethe functionofcrucial genesinT.gondii and discusshowsome experimental approaches contributetooreven favortheemergenceofalternativemechanisms toensure completion ofthe vitalstepofhostcellinvasion.
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