Medical Microbiology

Host–PathogenInteractions 19

region.Othervirulencegenescanalsobeactivatedbyregulatorsusing

thismechanism.

— Complexregulation,virulenceregulon.Inmanycases,severalvirulence

genesareswitchedonandoffbythesameregulatorprotein.Theviru-

lencedeterminantsinvolvedareeithercomponentsofthesameoperon

orarelocatedatdifferentgenomesites.Severalvir(virulence)geneswith

promoterregionsthatrespondtothesameregulatorproteinformaso-

calledvirregulon.RegulationofthevirulenceregulonofBordetellaper-

tussisbymeansofgeneactivationisacaseinpointthathasbeenstudied

ingreatdetail.Thisparticularreguloncomprisesover 20 virulencedeter-

minants,allcontrolledbythesamevirregulatorprotein(orBvgAcoding

region)(Fig. 1. 4 ).

&Posttranscriptionalregulation.ThistermreferstoregulationbymRNA

oraposttranslationalproteinmodification.

&Quorumsensing.Thistermreferstodeterminationofgeneexpression

bybacterialcelldensity(Fig. 1. 5 ).Quorumsensingisobservedinboth

RegulationofBacterialVirulence:Two-ComponentRegulatorSystem

Input signal

(external milieu)

Bacterial

membrane

Receiver

module

Membrane

anchor

Transmitter

module

Regulator

protein

Functional

module

Receiver

module

Virulence

regulon

Sensor

protein Virulence

determinants

Fig. 1. 4 Asensorproteinintegratedinthecytoplasmicmembranereceivessig-

nalsfromareceivermoduleextendingintotheexternalmilieu,activatingthe

transmittermodule.Thesesignalsfromtheexternalmilieucancarryawidevariety

ofinformation:pH,temperature,osmolarity,Ca2+,CO 2 ,stationary-phasegrowth,

hungerstress,etc.Thetransmittermoduleeffectsachangeinthereceivermodule

oftheregulatorprotein,switchingthefunctionalmoduleoftheregulatortoactive

status,inwhichitcanthenrepressoractivatethevariousvirulencedeterminants

ofavirulenceregulonbybindingtothedifferentpromoterregions.Phosphory-

lationiscommonlyusedtoactivatethecorrespondingsensorandregulator

modules.

1

Kayser, Medical Microbiology © 2005 Thieme