FoodBorneInfectionsand

Intoxications:

Listeriamonocytogenes
Campylobacterjejuni
Clostridiumbotulinum
Clostridiumperfringes
Bacilluscereus
Vibriocholera

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TIFF (Uncompressed) decompressor
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BackgroundandHistory
3,000,000,000yearsago
3,000,000yearsago
20,000yearsago
10,000BC

5,000BC
2,000BC
900AD
1202
18501900
1904
1916
1960
1984
1993

2005

FirstBacteria
FirstHumans
Agriculturalsocieties
Soups,breads,beer
Wine
cooking,drying,
smoking,freezing,
marinating,salting,
andpickling
Yogurt,cheeses
DietaryLaws
PopcornChocolate
SausageOutlawed
AssizeofBread
Handwashing
Pasteurization
Germsdiscovered
TyphoidMary
Refrigeration
HazardAnalysisand
CriticalControlPoint
(HACCP)
Rajneeshees
Jack in the Box E.
coli
Staph and money

Overviewoffoodborneillnesscase#'s,
illnesses,hospitalizationsanddeaths
(Table3)

Listeriamonocytogenes
Grampositiverods

Faculativeanaerobe
Nospores
Nocapsule
Motile1025oC
CloselyrelatedtoBacillus,Clostridium,
Enterococcus,Streptococcusand
Staphylococcus
Genushas6speciesL.monocytogenesandL.
ivanoviiarepathogenic

Listeriamonocytogenes
Majorpublichealthconcernbecause:
Severe,nonentericnatureofthedisease:
Highcasefatalityratecanbeashighas20
30%
Longincubationtime

Listeriamonocytogenes
Riskgroups
Pregnantwomenandneonates
Elderly
Immunocompromisedordebilitatedpeople:
Malignancy,antineoplastictreatment,immunosuppressed,
chronicliverdisease,collagendiseases(lupus),diabetes,
AIDS

Listeriamonocytogenes
PropertiesoftheOrganism:
Habitatandsourceswidelydistributed!(next
slide)
BottomlineManyfoodshavebeenimplicated
butfoodsmarketedasrefrigeratedandreadyto
eataretheonesthathavebeenassociatedwith
mostoftheoutbreaks.
HumanCarriage

Listeriamonocytogenes
Habitatandsources

Listeriamonocytogenes
Theorganismisbetahemolyticandiseasily
confusedwithhemolyticstreptococci.Listeria
mayalsogrowinshortchains.Docatalasetest!

Listeriamonocytogenes
GrowthandLaboratoryCharacteristics

Facultativeanaerobe
Theorganismishemolytic.
Itiscatalasepositive
Itisagrampositiverod
Itispsychrotropic
Theorganismismotile

Listeriamonocytogenes
Clinicalsignsaresimilarinallhosts:
Perinatallisteriosis
Adultlisteriosis

Botharedisseminatedinfectionoftenwith
CNSinvolvement

Listeriamonocytogenes
NeuromeningeallisteriosisinsheepCircling
Disease

Listeriamonocytogenes
Listeriosisinsheeppyogranulomatouslesions

Listeriamonocytogenes
HumanstillbornGranulomaosisinfantiseptica

Listeriamonocytogenes
TheDiseaseEntity:

Listeriamonocytogenes
Brainlesionsinsheep

Listeriamonocytogenes
Inadditiontoprofessionalphagocytessuchas
macrophages,theseorganismscaninvadeanumber
ofcelltypes:

Epithelialcells
Fibroblasts
Hepatocytes
Endothelialcells
Neuronsandpossiblyotherneuralcells

Listeriamonocytogenes
Internalization:
Hostfactors

Ecadherin,
CMet
GlobularC1qreceptor(complementreceptors),
glycosaminoglycans
fibronectinandintegrin

Listeriaadhesins:

InternalinA
InternalinB.
p60
Ami
Lap
fibronectinbindingprotein(24.6kDa).

Listeriamonocytogenes

InternalinA(InlA)
BindstoEcadherinintheadherensjunction,triggeringactincytoskeleton
rearrangementsviaassociationwithcatenins

Listeriamonocytogenes
InternalinA(InlA)
800aawith14N
terminalleucinerich
repeats
Leucinerichrepeat
structureona
serine/threonine
receptorkinase
BindstoEcadherinin
theadherensjunction,

Listeriamonocytogenes
InternalinA(InlA)
800aawith14N
terminalleucinerich
repeats
BindstoEcadherinin
theadherensjunction,
triggeringactin
cytoskeleton
rearrangementsvia
associationwith
catenins

Listeriamonocytogenes
Vacuoleformation,
proliferationand
spread:
phagosomeformation,
lysisandrelease
ListeriahemolysinHly
(alsoknownas
listeriolysinorLLO)
Listeria
phospholipases:PlcA
andPlcB
(phospholipaseCA
andB):

Listeriamonocytogenes
PhagocyticVacuole
formation
Phagosomeacidifies
Lysosomefusion
inhibited

Listeriamonocytogenes
Escapefromthe
PhagocyticVacuole
Listeriahemolysin,
(Hly,Listeriolysin,
LLO),
Cholesteroldependent,
poreformingweak
cytolysin

Listeriamonocytogenes

EscapefromthePhagocytic
Vacuole
Listeriaphospholipases:PlcA
andPlcB(phospholipaseCA
andB)
Roleinescapefromthe
phagosome
Escapefromthedouble
membranevessicleincellto
cellspread
Subverthostcellsignalling
pathways

Listeriamonocytogenes

Listeriainvasion

Listeriainvasion

Gastroenteritis

GutAssociatedLymphaticTissue

PeyersPatch

MCell

Campylobacterjejuni
Campylobacterjejuniistheleadingcauseof
gastroenteritisintheUSandprobably
worldwide..
Hawai'ihasthehighestincidenceinthe
countryabout900reportedcasesayear
withanincidenceof75/100,000,butthe
thinkingisthatinfectionsaregrossly
underreported.

Organism

Reservoirs HumanDisease

C.jejuni

Humans,
Diarrhea,systemicillness,
birds,other GBS
mammals

C.coli

Pigs,birds

C.lari

Birds,dogs Diarrhea

C.fetus

Cattle,
sheep

Diarrhea
Systemicillness,diarrhea

Otherrelatedorganismsinclude:
C.sputorum,C.concisus,C.curvus,Crectus,C.showae.

Arcobacteriumbutzleri,A.cryaerophilus,A.skirrowii

Campylobacterjejuni
Propertiesoftheorganism

Curvedsshapedgram()rods,motilewithasingle
polarflagellumatoneorbothends.
Defined"viablebutnotculturable"state.
respiratorymetabolism,microaerophilic.
Growwith10%CO2/5%O2.Somespecies/
strainsrequireadditionalH2intheatmosphere
C.jejuniwillgrowat42oCandthisisusedasa
selectioncriterion.
Theorganismisunusuallythin(0.20.9)

Campylobacterjejuni

Campylobacterjejuni
Reservoirsandepidemiology

Humancasesareassociatedwith:
Poultryespeciallyeatingchickenout
Petsespeciallyyoungpuppies
Watersupply
Rawmilk
Mostcasesoccurinthesummermonthslate
springtoearlyautumnthisisalsotrueinHawai'i.

Campylobacterjejuni

Campylobacterjejuni
PathogenesisandDiseaseCharacteristics
Lowinfectiousdose
Twodiseaseentities:
Diarrhea
Dysentery

AssociatedwithGuillaineBarrsyndrome

Campylobacterjejuni
Virulencefactors
Cjcaninvadeintestinalepithelialcells.
Cjsecretesanumberofnovelproteinsuponcultivationwith
enterocytes:
CiaB

pVir,presentonlyinsomestrainsofCjappearstobeimportant
forinvasion.
Microtubulemediatedendocytosisoccurs
Cjapparentlystayswithinvacuole
adenylcyclaseactivatingcholeratoxinlikeenterotoxin

cytotoxin

Campylobacterjejuni

Virulencefactors
Microtubulemediatedendocytosisoccursandmicrofilamentmechanismmaybe
involvedtoo
MicrotubulesaggregateintofingerlikeprotrusionswithC.j.atthetips

Campylobacterjejuni
Virulencefactors
CytolethalDistendingToxin
Irreversablecellcyclearrest
AllthreeCDTgenesneedtobeexpressedfor
activity

Adenylcyclaseactivatingenterotoxin?

Campylobacterjejuni
GuillaineBarrSyndrome
Ascendingmuscleweaknessorparalysis,
rapidlyprogressing
40%ofGBSpatientshaveevidenceof
Campylobacterinfection
Penner1,2,8,17,19,41aredisproportionately
represented
LPSoligosaccharidesstructurallyrelatedto
humanmotorneurongangliosides

Bacilluscereus
Causestwotypesoffoodborneillness:
Diarrhealdisease
Emeticdisease

Bacilluscereus
Species
B.cereus
B.
anthracis
B.
thuringens
is
B.
mycoides

Colony
morph.
white

Crystal
Inclusions

white

Whiteor
gray

Rhizoid

(+)

Hemolysis Motility

Bacilluscereus
Grampositivelarge(width>1um)rod,
sporeformercentralsporeorparacentral
growsaerobicallyandanaerobically
betahemolytic
usuallymotile
maybepresentinstoolsofhealthyindividuals
grownoutoffoodsamplesafterheatshock>treatsampleat70 o
Cfor10minutes;orafterethanolshock>mix1:1withabsolute
ethanolfor1hour
Widelydisseminatedinnature

Rice,spicesanddairyproducts

Bacilluscereus
Diseaseentities:
Twotypesoffoodborneillness:

Emeticemetictoxin,foodintoxication
circularpeptide,1.2kDa,calledcereulide
Stimulatesthevagusnerveleadingtotheemeticresponse.

Diarrhealenterotoxin,foodinfection
Atleastthreeenterotoxinshavebeendescribed

Bacilluscereus
Diarrhealvs.EmeticDisease
Characteristic
Diarrheal
Emetic
InfectiveDose 105107cells
105108perg
Toxinproduced: Insmall
Infood
intestine
Toxintype
Protein
Cyclicpeptide
enterotoxin
Incubation
816hours
30min5hours
period
Duration
1toseveraldays 624hours

Bacilluscereus

Diarrhealvs.EmeticDisease
Characteristic
Diarrheal
Emetic
Symptoms
Abdpain,
Nausea,
waterydiarrhea, vomiting,malais
somenausea
e,diarrheaif
enterotoxinalso
produced
Foods
Meat,soups,
Friedrice,
vegetables,
cookedrice,
puddings,
pastaand
sauces,milk
noodles,pastry

Clostridiumbotulinum

Grampositiverod
anaerobic
sporeformer
seventypesbasedonserologicspecificityof
neurotoxinnamedAthroughG
A,B,EandsometimesF>causesofhumanbotulism
CandD>animalbotulism,contaminatedfeed.
G>noclearassociationwithdisease

Clostridiumbotulinum

Clostridiumbotulinum
Reservoirs

Clostridiumbotulinum
FoodSources

Clostridiumbotulinum
DiseaseCharacteristics:
Symptomshit1236hoursafteringestion(sometimessooner,
sometimesweekslater!)

nauseaandvomiting(BandE)
visualimpairment:blurred,ptosis,dilatedpupils
lossofmouthandthroatfunction(AandB)
drymouth,throat,tongue,sorethroat
fatigueandlossofcoordination
respiratoryimpairment
abdominalpainandeitherdiarrheaorconstipation

Clostridiumbotulinum
InfantBotulism:

constipationdaystoweekafteronset
generalizedweaknessandaweakcry
poorfeedingandsuckingreflex
lackoffacialexpression
floppiness
respiratoryarrestmayoccuralthoughdeathisrare.

Clostridiumbotulinum
VirulenceFactors
Neurotoxin(BoNT)
watersoluble
producedasasinglepolypeptide150,000MW(progenitor)
cleavedbyaproteasetoformtwopolypeptideswhichthen
becomeSSbonded:100,000and50,000MW
Therearedifferencesinserotypes:

A=dimer,trimer,andcanbelarger
E=monomeranddimer

B=dimer
A,B,E,Farechromosomallyencoded

C,Darephageencoded
Gisplasmidencoded

Clostridiumbotulinum
architectureofthemotorend
plate
Motorneuron

Synapticcleft

Musclecell

Clostridiumbotulinum
Synapticvessicle

Synaptobrevin
(VAMP):
BoToxB,D,F,G
SNAP25:
BoToxA,E

Syntaxin
(HPC1):
BoToxC

Synapticcleft

Motorendplateofthemusclecell

Clostridiumperfringes
TypeAfoodpoisoning
Necrotizingenteritis(Enteritisnecroticans)alsoknownas
DarmbrandorPigbelcausedbyTypeC

Grampositiverod
Sporeforming
anaerobicbuttolerantofsomeexposuretoair
underoptimalconditions,iscapableofdoublingevery10
minutes

ubiquitousdistributionfecesandsoil

Clostridiumperfringes
TypeA

Symptoms824hoursafteringestion
Resolution1224hourslater

Diarrheaandcramps(severe)
Novomiting
Nofever
Maybeseriousintheelderly

Clostridiumperfringes
Infectionorganismsmultiplyandthensporulateinthesmallintestine.
CPE(Clostridiumperfringesenterotoxin)isreleasedduringthe
sporulationprocess.

CPEisasinglepolypeptide,35000Da
heatlabile(destroyedbyheating5at60 oC)
Bindstomembranereceptorwhichinvolves2membraneproteinsonthe
targetcell50and70kDa(Fig7and8).
Insertsintothemembraneandisbelievedtocauseamembranelesionwhich
thenalterspermeabilityfluidandelectrolytelossanddamagetothe
epithelium.Glucoseisstillabsorbed.

Clostridiumperfringes

Clostridiumperfringes

Vibriocholera

Whoops!
sorry

Overviewoffoodborneillnesscase#'s,
illnesses,hospitalizationsanddeaths
(Tables1and2)

Overviewoffoodborneillnesscase#'s,
illnesses,hospitalizationsanddeaths
(Tables1and2)