Microbiology and Immunology 4100A Lecture Notes - Lecture 16: Cytotoxicity, Enterotoxin, Exotoxin

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A bservestodesignatetwodomains partofdifferentsubunitsinoligomerictoxinsthatislatercleaved theadomaindenotestheportionofthetoxinthatcarriestheenzymaticactivity thebdomaindenotestheportionofthetoxinmoleculeresponsibleforbindingtothecellmembranereceptor bbinding the adomainisoftenclearedfromthebdomainbya hostproteaseandisthenlinkedthrougha ssbond. Clathrindependentendocytosis il n p themostcommonmechanism is a normalcellularprocess process. Arenotsubjectedtophdependentchanges throughretrogradetranslocation it willgetprocessedthroughthetransgolginetworktothegolgi andthentothelumenoftheer viaproteinconductingchannels toxinswillgetreleasedintothecytosoltoperformitsenzymaticfunctions: cterminalredlkmotifispresentonexotoxina similartokdelsequenceonresidenterproteins if hostproteinsescapetheer thelaserreceptor ligandcomplexreturnstheproteinsbacktotheer toxinsusethissequencetogetintotheer. Colonizationandgrowthcorynebacteriumdiptheriaeintheupperrespiratorytractwithtoxinproduction characteristicswollenneck piptheriatoxinisthemajorvirulencefactor toxininducesnecrosisandinflammation formationof a pseudomembrane canleadtosuffocation toxindissemination cancauseheartandnervoussysteminflammation. Vaccinehaseradicateddiptheriainthedevelopedworld is a singlepolypeptide 63kda whichisclearedinsidetheendosometoformaandbfragments linkedby a singledisulfidebridge thedtgene isencodedbyalysogenicphage. Adpribosylationofdipthamide a modifiedhistidinespecificelongation factor 2 ef2 causesa blockinproteinsynthesisresulting incell death. The asubunit of ct appribosylatesthe x subunitofthestimulatory 6protein gs which lockstheenzymeinitsgtpboundformbecausegtp gdp pi is inhibitedcausingconstitutive activationofhostadenylatecyclase. Tdapisusedas a boostervacine pertussistoxinis a noncovalentmultiproteinhexamericcomplex composedof 5differentpolypeptides s1 s2s3s4 s5in a ratio 1 i l 2 l. Gastrointestinal ingestionofspores veryrarebutoftenfatal bacteriaareusuallycontainedandinfectionwillresolve inhalation mostdangerous aerosolizedsporescc5pmgetphagocytosedbyalveolarmacrophages sporeswillgerminateandtransporttothelymphnodesleadingtorapiddisseminationtothe blood ifuntreatedistoo fatal. B anthraciscontains a plasmids pxo encodes 3anthraxtoxinproteins pxoa encodesantiphagocyticcapsule lackofeitherplasmid nonvirulent lackofbothplasmids basicallyhavebcereus. Differentcombosof leandiorefcanbind willinvaginatein aclathrincoatedpittoformanearlyendosome susceptibletoacidicphofearlyendosome if hecamein it is a proteasethatisspecifictomapkks protease metallo. Le adenylate cyclase ee cleavageofmapiceleadstoapoptosisofthecell whichisusuallya macrophage if efcamein itinteractswithca andcalmodulin causingcampproductionandedemaofthecell.

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