Medical Microbiology

256 4 BacteriaasHumanPathogens

Diphtheriatoxin

FragmentAisanADPribosyltransferase.Theenzymetransfersadenosinedi-

phosphateribosefromNADtotheelongationfactoreEF2,therebyinactivatingit:

NAD+eEF2!ADPribosyleEF2+nicotinamide+H+

eEF2“translocates”thepeptidyltRNAfromtheaminoacidpositionAtothepeptide

positionPontheeukaryoticribosome.Althoughthetoxingeneisintegratedina

phagegenome,itsactivityisregulatedbythegeneproductDtxRofthedtxRgene

ofthebacterialcell’sgenome.DtxRcombineswithFe2+tobecomeanactivere-

pressorthatswitchesoffthetranscriptionofthetoxingene.

PathogenesisandClinicalPicture

&Localinfection.Infectionofthemucosaoftonsils,pharynx,nose,and

conjunctiva(Fig.4. 10 ).Woundsandskinlesionscanalsobeinfected.The

pathogensinvadethehostthroughtheseportals,reproduce,andproduce

toxin,resultinginlocalcelldamage.Theinflammatoryreactionleadstocol-

lectionofagrayish-whiteexudate,thematrixofthe“diphtherialpseudo-

membrane”consistingoffibrin,deadgranulocytes,andnecroticepithelial

cells.Thiscoatingadheresquitestronglytothemucosa.Itmayextend

intothelarynx,thuseventuallyhinderingrespiration.Regionallymphnodes

arehighlyswollen.

&Systemicintoxication.Parenchymaldegenerationinthecardiacmuscle,

liver,kidneys,andadrenalglands.Motorcranialnerveparalysis.Latesequel

damageduetotheintoxicationisfrequentlyseenaftertheacuteinfectionhas

subsided.

Toxin-negativestrainsofC.diphtheriaeareoccasionallyobservedaspatho-

gensinendocarditisordermalinfections.Thepathogenicityofsuchstrains

correspondstothatofcommensalcorynebacteria(seeTable4. 3 ,p. 26 1).

Diagnosis.Themethodofchoiceisdetectionandidentificationofthepatho-

geninculturesfromlocalinfectionfoci.Theculturesmear,whicharrivesat

thelaboratoryintransportmedium,isplatedoutonLo ̈fflermediumanda

selectiveindicatormedium.Identificationisbasedonbothmorphological

andphysiologicalcharacteristics.ThetoxinisdetectedbytheElek-Ouchter-

lonyimmunodiffusiontest.Amolecularmethodisnowalsobeingusedto

identifythetoxingene.Toxindetectionisnecessaryforalaboratorydiagnosis

ofdiphtheriabecauseoftheoccurrenceoftoxin-negativestrains.

Therapy.Antitoxicserumtherapyistheprimarytreatmentanditmustcom-

menceassoonaspossibleifdiphtheriaissuspected.Thistreatmentissup-

plementedbyadministrationofpenicillinorerythromycin.

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Kayser, Medical Microbiology © 2005 Thieme