Medical Microbiology

18 1 GeneralAspectsofMedicalMicrobiology

&Cellwall.TheendotoxinofGram-negativebacteria(lipopolysaccharide)

playsanimportantroleinthemanifestationofclinicalsymptoms.Ontheone

hand,itcanactivatecomplementbythealternativepathwayand,byreleas-

ingthechemotacticcomponentsC3aandC5a,initiateaninflammatory

reactionattheinfectionsite.Ontheotherhand,italsostimulatesmacro-

phagestoproduceendogenouspyrogens(interleukin 1 ,tumornecrosisfac-

tor),thusinducingfevercentrally.Productionoftheseandothercytokinesis

increased,resultinginhypotension,intravasalcoagulation,thrombocyteag-

gregationandstimulationofgranulopoiesis.Increasedproductionofcyto-

kinesbymacrophagesisalsoinducedbysolublemureinfragmentsand,in

thecaseofGram-positivebacteria,byteichoicacids.

&Inflammation.Inflammationresultsfromthecombinedeffectsofthe

nonspecificandspecificimmuneresponsesofthehostorganism.Activation

ofcomplementbywayofboththeclassicandalternativepathwaysinduces

phagocytemigrationtotheinfectionsite.Purulenttissuenecrosisfollows.

Thedevelopmentoftypicalgranulomasandcaseousnecrosisinthecourse

oftuberculosisaretheresultsofexcessivereactionbythecellularimmune

systemtotheimmunogensoftuberculosisbacteria.Textbooksofgeneral

pathologyshouldbeconsultedfordetaileddescriptionsoftheseinflamma-

toryprocesses.

RegulationofBacterialVirulence......................

Manypathogenicbacteriaarecapableoflivingeitheroutsideorinsideahost

andofattackingavarietyofhostspecies.Proliferationinthesedifferingen-

vironmentsdemandsanefficientregulationofvirulence,theaimbeingto

havevirulencefactorsavailableasrequired.Fourdifferentregulatorymech-

anismshavebeendescribed:

&DNAchanges.Thenucleotidesequencesofvirulencedeterminantsare

changed.Examplesofthisincludepilingenevariabilityinvolvingintracellu-

larrecombinationasdescribedaboveingonococciandinvertingaleaderse-

quencetoswitchgenesonandoffinthephasevariationsofHantigensin

salmonellae(seep.284).

&Transcriptionalregulation.Theprincipleoftranscriptionalcontrolof

virulencedeterminantsisessentiallythesameasthatapplyingtotheregu-

lationofmetabolicgenes,namelyrepressionandactivation(seep. 1 69f.):

— Simpleregulation.Regulationofthediphtheriatoxingenehasbeenthor-

oughlyresearched.Aspecificconcentrationofironinthecytoplasmac-

tivatesthediphtheriatoxinregulator(DtxR).Theresultingactiverepres-

sorpreventstranscriptionofthetoxingenebybindingtothepromoter

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Kayser, Medical Microbiology © 2005 Thieme