Name:

-Zai
nAbbas
Rol
lNo:
-9837
Pr
ogr
am:
-DPT(
6th)
Submi
tt
edt
oMa'
miqr
aNawaz
Q:
-Cl
ost
ri
dium Speci
es
I
mpor
tantpr
oper
ti
es
Cl
ini
calFi
ndi
ngs
Pat
hogenesi
s
Labdi
agnosi
s

Cl
ost
ri
dium speci
es
:
-Clostr
idium speciesar eanaerobic,f
ermentati
v e,spore-
for
mingGr am-positi
vebacteriabelongi
ngtot hephy lum
Fir
micutes.Toxin-producingspeciescancausemi ld-to-
fat
alfoodpoi soning,mostf amouslyClostr
idi
um
botul
i
num andCl ostri
dium perfr
ingens.Sever
al other
Cl
ost
ri
dium speci
escancausemeatspoi
l
age.
:
-Clostri
dium speci
es(Clost
ridi
um perfr
ingens,C.
buty
ricum, C.cl
ostr
idi
oforme,C.innocuum, C.r
amosum,
C.
septi
cum, C.sordel
li
i,
C.tert
ium)

Hi
stor
y:-
:
-Int
hel
ate1700s,
Ger
manyexper
iencedanumberof
out
breaksofanil
lnessthatseemedconnectedtoeat
ing
cer
tai
nsausages.In1817,theGermanneurologi
st
Just i
nusKer nerdetectedrod-shapedcel lsinhis
i
nv estigationsintothisso-cal
ledsausagepoi soning.In
1897, theBel gianbiologyprofessorEmi l
evanEr mengem
publ i
shedhi sf i
ndingofanendospor e-formingor ganism
hei solatedf r
om spoiledham.Bi ologistsclassif
iedv an
Ermengem' sdiscoveryalongwi t
hot herknowngr am-
posi t
ivespor ef or
mer sinthegenusBaci ll
us.This
cl
assi ficati
onpr esentedproblems, howev er,becauset he
i
sol ategr ewonl yinanaerobiccondi t
ions,butBaci l
lus
grewwel l i
noxy gen.

:
-Ci
rca1880,
int
hecour
seofst
udy
ingf
erment
ati
onand
butyri
cacidsynthesi
s, ascient
istsurnamedPr azmowski
fi
rstassi
gnedabi nomi alnamet oClostri
dium
butyri
cum.[Themechani smsofanaer obicr espir
ati
onwer
e
sti
llnotyetwell
elucidatedatthatti
me, sotaxonomyof
anaerobeswasst il
lnascent.

:
-I
n1924,
IdaA.Bengt
sonsepar
atedv
anEr
mengem'
s
mi cr
oorgani
smsf rom theBaci l
l
usgroupandassigned
them tothegenusCl ostr
idium.ByBengtson'
s
classi
fi
cati
onscheme, Cl
ost r
idi
um cont
ainedall
ofthe
anaerobicendospore-f
ormi ngrod-
shapedbacteri
a,except
thegenusDesul f
otomacul um.

:
-Amongmor
ethan200knownCl
ost
ri
dium spp.atl
east
30ar eassoci atedwi t
hhumandi sease.Theyusual l
y
appearasgr am- posi t
iverods, howev ermanyst rainsmay
appeargr am- variableorgr am- negat iv e.Lossofgr am-
positi
veappear anceoccur swi thdi rectst ainsofcl ini
cal
mat eri
alorincul turesaf terprolongedi ncubationori n
specieswi t
ht ermi nal spores.Cl ost r
idi um per fr
ingensi s
themosti mpor tantoft hespeci esandaccount sf or20-
40%ofal li
solates.Speci at i
oni sbasedmost lyoncel l
ular
mor phology,spor esl ocation(cent r
al, termi nalorsub
terminal),
biochemi cal r
eact i
ons, gasl iquid
chromat ographyf orferment ationpr oduct s;andt he
demonst rati
onofpr oductionofl ecithinase( oralphat oxin
byC.per fri
ngens)andl i
pase( byCl ost ridi
um spor ogenes,
Clostri
dium nov y iandCl ostri
dium bot ulinum.
:
-Cl
ost
ri
dium i
sagenusofGr
am-
posi
ti
vebact
eri
a.Thi
s
genusi ncludessev eralsignifi
canthumanpat hogens,
i
ncl udi ngt hecausat i
v eagent sofbot uli
sm andt etanus.
Thegenusf or merlyincludedani mpor tantcauseof
diarrhea, Clostri
dioidesdi ffi
cil
e, whichwasr ecl
assifi
ed
i
nt ot heCl ostri
diodiesgenusi n2016.Theyar eobligate
anaer obescapabl eofpr oducingendospor es.Thenor mal,
reproduci ngcel l
sofCl ostridi
um, calledt hev egetative
form, arer od-shaped, whichgi vest hem t heirname, fr
om
theGr eekκλωστήρorspi ndle.Cl ost ri
dium endospor es
hav eadi st i
nctbowl i
ngpi norbot tl
eshape, dist
inguishing
them f rom ot herbact eri
al endospor es,whi char eusual l
y
ovoi di nshape.Cl ostridi
um speci esi nhabitsoi l
sandt he
i
nt estinal tractofani mal s,incl
udi nghumans.Cl ostri
dium
i
sanor mal inhabitantoft heheal thyl owerr eproductive
t
ractoff
emal
es.

:
-Thegenus,
ast
radi
ti
onal
l
ydef
ined,
cont
ainsmany
organismsnotcl oselyr elatedtoitst ypespeci es.The
i
ssuewasor iginal
lyil
lust r
atedinf ul
l detailbyar RNA
phylogenyfrom Col l
i
ns1994, whichspl itthet r
aditi
onal
genus( nowcor respondi ngt oalargesl iceofCl ostridi
a)
i
ntot wentyclusters,withcl ust
erIcont aini
ngt het ype
speciesandi tscloserel ati
ves.Overt hey ears,thishas
result
edinmanynewgener abeingspl i
tout ,withthe
ult
imat egoalofconst rainingClost r
idium tocl usterI.

:
-"Cl
ost
ri
dium"cl
ust
erXI
Vaand"
Clost
ri
dium"cl
ust
erI
V
effi
cient
lyfermentplantpol y
sacchar i
decomposing
diet
ar yf
iber,
makingthem impor tantandabundanttaxain
therumenandt hehumanl argeintest
ine.
Asmentioned
before,thesecl
uster
sar enotpar tofcurr
ent
Clostri
dium,anduseoft heset er
msshoul dbeavoideddue
toambi guousorinconsistentusage.

EPI
DEMI
OLOGY
OrganismsofthegenusCl ostr
idi
um areimpor t
ant
member softhehumans’ anaerobi
cgastroint
estinaland
cervi
cal-
vagi
nalf
lor
a.Clostri
diaareubiqui
tousandar e
foundinthesoi
l,mari
nesedi ment,decayi
ngv egetat
ion
andintest
inal
tractofhumans,ot
hervertebr
ateand
i
nsects.Humani nfect
ionswit
hclost
ri
diacanresul
tfr
om
endogenousorexogenousi nf
ect
ion.
:
-Howmanyspeci
esofCl
ost
ri
dium ar
ether
e
Clostr
idi
um contai
nsaround250speci est hatinclude
commonf r
ee-l
ivi
ngbacteri
a, aswellasimpor t
ant
pathogens.Themai nspeciesresponsibl
ef ordiseasein
humansar e:Clost
ri
dium botuli
num canproduce
botul
inum toxi
ninfoodorwoundsandcancausebot ul
i
sm.
:
-Wher
eisCl
ost
ri
dium f
ound
Clostr
idi
um,genusofr
od-
shaped,usuall
ygram-
positi
ve
bacteri
a,membersofwhi
charefoundinsoil
,water
,and
theint
esti
nalt
ract
sofhumansandot herani
mals.
:
-Whatdi
seasei
scausedbyCl
ost
ri
dium
Clostri
dium di
ff
icil
e(klos-
TRID-e-um dif
-uh-
SEEL),
also
knownasCl ost
ridioi
desdif
fi
ci l
eandof t
enrefer
redtoasC.
dif
fici
leorC.diff
, i
sabacterium thatcancausesympt oms
rangingfrom di
ar r
heatoli
fe-threat
eninginf
lammationof
thecolon.
I
mpor
tantPr
oper
ti
es
:
-Genusofr
od-
shaped
:
-Usual
l
ygr
am-
posi
ti
vebact
eri
a
:
-Member sofwhi
charefoundi
nsoil,
water
,andt
he
i
ntest
inal
tract
sofhumansandotherani
mals.
:
-Mostspeci esgr
owonlyi
nt hecompl et
eabsenceof
oxygen.Dormantcel
l
sarehighlyresi
stanttoheat,
desiccat
ion,
andtoxi
cchemicalsanddet er
gents
:
-Clost
ri
dium i
sagenusofgr
am-posi
ti
ve,spore-
for
ming
bact
eri
abelongi
ngtothef
amil
yClost
ri
diaceae.
:
-Veget ati
vecellsarerodshapedandar r
angedinpairsor
shortchai
ns.Themaj or
it
yofspeci esar eobli
gate
anaerobes;howev er
,somespeci escangr owunder
aerobi
ccondi t
ionsorareaerotoler
ant .Therearecloseto
200speciesofCl ostr
idi
um, wit
honl yaf ewspeciesbeing
pathogenictohumans.Sev eralspeciespr oducetoxi
ns.
Cl
ini
calFi
ndi
ngs
:
-Inf
ect
ionscausedbyt
heseor
gani
smsr
angef
rom a
varietyoflocali
zedwoundcont aminat i
ont oov erwhelmi ng
systemi cdisease.
Clostri
dialhistiot
oxi csyndr omesar e
medi atedbyt oxi
nsandi ncludesof ttissuei nfectionssuch
asgasgangr ene(causedbyC.per fringens) ,enteri
c
diseasessuchascl ostri
dialf
oodpoi soning, enterit
is
necr oti
cans,anti
bioti
cassoci atedcol i
tis(causedbyC.
diff
icile),di
scussedelsewher e, andneut r
openi c
enter ocol
iti
s(causedbyC.sept icum)andneur ological
syndr omessuchast etanusandbot ulism (bot hdiscussed
elsewher e).
:
-C.sept
icum cancausespont
aneous,
non-
tr
aumat
icgas
gangr ene,andC.sor dell
iicaninducegasgangr eneofthe
uterus, asaconsequenceofspont aneousabor t
ion,
normal vagi
nal deli
veryandt raumat icinjury.
Clostr
idi
al
bacter emiaaccountf orcli
nicall
ysignificantanaerobic
bacter emiasecondonl ytoBact eroidesspp.Cl ostri
diaar
e
al
soof tenisolatedfrom pol ymicrobiali
nt r
aabdomi nal
,
bi
liary,pleuropulmonar y,centralnervoussy stem,
genitour i
naryandski nandsof tti
ssuei nfecti
ons.

:
-Bl
oodsampl
es,
whi
chwer
eobt
ainedf
rom pat
ient
swho
l
ivedinar uralareawi thappr oximat ely500acut e-care
hospital beds, wer ecul t
uredf rom 1990t hrough1997.We
retr
ospect iv
elyr evi
ewedt hebl oodcul turesthaty iel
ded
Clostr
idium speci es( 74[0.12%]of63, 296cul tures).These
wereobt ainedf rom 46di f f
erenthospi tali
zedpat ients
(i
ncident sperhospi tal,0.03%) .Thesour ceoft he
Clostr
idium speci eswasagast roi
ntestinalsitein24
pati
ent s( 52.2%) .Themostf requentlyident i
fi
ed
Clostr
idium speci eswasCl ostri
dium per fr
ingens( in10
[
21.7%]ofpat ients),
f oll
owedbyCl ostri
dium sept icum (i
n
9[19.6%] ).Thi rt
y -
onepat ients( 67.4%)wer eaged>or=65
years,13pat i
ents(28. 3%)haddi abetesmel l
it
us, and
underlyingmal ignancywaspr esenti n22pat i
ents( 47.
8%) .
Themor tal i
tyrateofpat i
ent swhosecondi tionhadbeen
managedsurgicall
ywas33%; forthosepat ientswhose
condit
ionsr
equiredmedicalmanagement ,themor tali
ty
rat
ewas58%.Cl ostri
dium bacteremiai nthesepat i
ents
usuall
yhadagast r
oint
esti
nal source,itoftenoccur r
edi n
pati
entswit
hseriousunderlyi
ngmedi calcondi t
ions,andit
rar
elywastheresultoftr
aumat icfarm acci dents.

Pat
hogenesi
s
:
-Toxi
nsmedi
atet
heCl
ost
ri
dial
hist
iot
oxi
csy
ndr
omes.
Toxinsarebiol
ogicallyact
iveprot ei
nst hatareant i
genic
andcapableofneut rali
zat
ionbyspeci f
icant i
sera.C.
perf
ringensproduces4maj orl
et haltoxins,basedon
whichitiscl
assifi
edi nt
o5ser ologicaltypesclassifiedA
toE.Additi
onalvir
ulencefactorsi ncl
udeent erotoxin,
neuraminadaseandhaemol ysi
ns.Ther oleofclostridi
ain
thepathogenesisofpol mi
crobial i
nfectionsisunclear.

:
-Cl
ost
ri
dium per
fri
ngensi
sthemostcommoncl
i
nical
i
solateoft hegenus.I
tisaubi quit
ousbact er
ium
associatedwithsever
al exotoxin-
medi at
edcl i
nical
diseases.Thereare12r ecognizedtoxins,andt hespeci
es
i
sdi vi
dedintotypesAt hroughEont hebasi softhe
spectrum oftoxi
nsproduced.Thedi seasesy ndromes
causedbyC.per fri
ngensar efoodpoi soning,necrot
izi
ng
ent
eri
ti
s,andgasgangr
ene.
Clostr
idi
um contai
nsaround250speciesthati
nclude
commonf r
ee-l
i
vingbacter
ia,aswellasimpor
tant
pathogens.
Themai nspeciesresponsi
blef
ordiseasei
n
humansar e:
-

:
-Cl
ost
ri
dium bot
uli
num canpr
oducebot
uli
num t
oxi
nin
foodorwoundsandcancausebot uli
sm.Thi
ssamet oxi
n
i
sknownasBot oxandi susedi ncosmeti
csurger
yto
paral
yzefaci
almuscl
est oreducethesignsofagi
ng;i
t
alsohasnumerousothertherapeuti
cuses.

:
-Cl
ost
ri
dium per
fri
ngenscausesawi
der
angeof
symptoms,fr
om foodpoi
soni
ngtocell
uli
ti
s,f
asci
i
tis,
necr
oticent
eri
ti
sandgasgangrene.

:
-Cl
ost
ri
dium t
etani
causest
etanus.

:
-Cl
ost
ri
dium sor
del
l
ii(
nowPaeni
clost
ri
dium)cancausea
fat
ali
nfecti
oni
nexcept
ional
l
yrar
ecasesaf
termedi
cal
abort
ions.

Bacil
lusandClost
ri
dium ar
eoftendescr
ibedasGr
am-
vari
able,
becausetheyshowani ncr
easi
ngnumberof
gram-negat
ivecel
lsasthecul
tureages.
Clostr
idium andBaci l
l
usar ebothinthephylum Fi
rmicut
es,
buttheyar eindif
ferentclasses,
orders,
andf amil
i
es.
Microbiologi
stsdist
inguishClostr
idi
um from Baci
ll
usby
thefoll
owi ngfeat
ures:-

:
-Cl
ost
ri
dium gr
owsi
nanaer
obi
ccondi
ti
ons;
Baci
l
lus
gr
owsi
naer
obi
ccondi
ti
ons.

:
-Cl
ost
ri
dium f
ormsbot
tl
e-shapedendospor
es;
Baci
l
lus
f
ormsobl
ongendospor
es.

:
-Cl
ost
ri
dium doesnotf
ormt
heenzy
mecat
alase;
Baci
l
lus
secr
etescat
alaset
odest
royt
oxi
cby
product
sofoxy
gen
metabol
ism.
Clostr
idium andDesul f
ot omacul um arebothi nt hecl
ass
Clostr
idiaandor derClostri
diales,andt heybot hproduce
bottl
e-shapedendospor es,buttheyar eindifferent
famil
ies.Clostri
dium canbedi sti
nguishedf rom
Desulfotomaculum ont hebasi soft henut r
ientseach
genususes( t
hel at
terrequiressulfur)
.
Gl
ycolysi
sandfermentat
ionofpyruvi
cacidbyCl
ostr
idi
a
yi
eldtheendproduct
sbutyri
caci
d, but
anol,
acet
one,
i
sopropanol
,andcarbondioxi
de.
TheSchaef
fer
-Fult
onstai
n(0.
5%mal achi
tegr
eeninwater
)
canbeusedtodisti
ngui
shendospor
esofBacil
lusand
Clostr
idi
um from othermicroorganisms.
Thereisa
commer cial
lyavai
lablepoly
mer asechainreact
ion(PCR)
testki
t(Bactoty
pe)f ort
hedet ecti
onofC.perfr
ingensand
otherpathogeni
cbact er
ia.

Labdi
agnosi
s
:
-Isolati
onofCl ostridiafr
om wound, pus, bl
oodorf aeces,
al
ongwi thtoxinandser ologicalassaysai dinthe
di
agnosi sofclostr
idi ali
nfections.Thesi gnif
icanceof
cl
ostridi
ainpoly micr obi
alisolatesisunknown.Cl i
nical
di
agnosi sisespecial l
yimpor tantininfecti
onssuchasgas
gangreneinwhi chdemonst r
at i
onofcl ostri
dial
my onecrosisi
scr i
tical i
nthedi agnosis.
:
-Thel abor atorydi agnosisofCl ostr
idium diff
icil
e-
associateddi sease( CDAD)i sbasedoncul tureandt oxi
n
detecti
oni nf ecal specimens.Cul tur
ei sper f
ormedona
commer ciall
yav ailableselecti
vemedi a.C.di ff
icil
ecolony
mor phologyi stypi calwhenv iewedunderadi ssect i
ng
microscope.Def initivei
dentifi
cati
oni sbestobt ainedby
gasl i
quidchr omat ography.Cultureisv erysensiti
vebut,
whenusedal onewi thouttoxintesti
ng, i
tleadst olow
specifi
cityandmi sdi agnosisofCDADwhenhi ghr at
esof
asympt omat iccar riageexist.Toxindet ecti
onbyat i
ssue
culturecy t
otoxi nassayf ollowedbyneut ralisationwi t
h
specificant i
serum i sof tenconsi deredt hest andard.
Howev er,t
hisappr oachl ackssensi ti
vityandhasnot
detectedupt o30%ofpat ient swi t
hconf irmedCDAD.
Mul ti
pleenzy mei mmunoassay s( EIAs)hav ebeen
i
nt r
oducedbyv ar i
ousmanuf acturersf ort hedet ectionof
toxinAal oneorf orbot ht oxinsAandB.Someoft hesear e
designedt ogi ver esultsi nlesst han1h.Compar ati
v e
studiesofEI Aki tsr eportedt hatt hesensi tivityand
specificit
yar eslight l
ylowert hancy totoxinassay s.
Toxigeni cculturet estsC.di ffi
cileisolatesf ort oxin
product i
on: coloniesi solatedonsel ectivemedi aar e
testedf orin-vi
trot oxinpr oduct ionei therbyacy totoxici
ty
assayorbydi r
ectEI A.Ithashi ghersensi tivitythant he
cytotoxicit
yassayandequi valentspeci fi
city .Inther outi
ne
l
abor atory,cultureandt oxindet ectionshoul dbe
performedonev eryspeci menand, i
ncul tur e-posi t
iveand
fecaltoxin-negat ivecases, toxigeniccul tur esshoul dbe
performedoni solatedcol oni es.

Uses:
-
:
-Clostr
idi
um thermocell
um canuselignocel
lul
osicwaste
andgenerateethanol
,thusmakingitapossiblecandi
date
foruseinproducti
onofethanolfuel
.Ital
sohasnooxy gen
requi
rementandi
sther
mophi
l
ic,
whi
chr
educescool
i
ng
cost.
:
-Clost
ri
dium acetobut
yli
cum wasfir
stusedbyChaim
Weizmanntopr oduceacetoneandbiobut
anolf
rom st
arch
i
n1916f ort
hepr oduct
ionofcordi
te(smokel
ess
gunpowder)
.
:
-Cl ostridium botul
inum pr oducesapot enti
all
ylethal
neur otoxinusedi nadilutedf orminthedr ugBotox, which
i
scar efull
yinj
ectedt onerv esintheface, whichpr events
themov ementoft heexpr essivemuscl esoft heforehead,
todel ayt hewr i
nkli
ngeffectofagi ng.Itisalsousedt o
treatspasmodi ctorti
coll
i
sandpr ovidesr eli
efforaround
12t o16weeks.
:
-Clostr
idi
um butyr
icum MIYAIRI588strai
nismarketedi
n
Japan,Korea,
andChi naforClost
ri
dium di
ffi
cil
e
prophyl
axi
sduet oitsrepor
tedabil
it
ytointer
ferewi
ththe
growthofthelat
ter
.
:
-Cl ostri
dium histol
yticum hasbeenusedasasour ceof
theenzy mecol l
agenase, whi
chdegradesani mal ti
ssue.
Clost r
idi
um speci esex cretecoll
agenasetoeatt hrough
ti
ssueand, thus,helpt hepathogenspreadt hroughoutthe
body .Themedi calprof essi
onusescollagenasef orthe
samer easoni nthedébr i
dementofinfectedwounds.
Hy aluronidase,deoxyribonuclease,l
eci
thinase,leukoci
din,
prot
ease,l
i
pase,andhemolysi
narealsopr
oducedby
someclostr
idi
athatcausegasgangr
ene.
:
-Clostri
dium lj
ungdahli
i,r
ecentl
ydi scov eredin
commer ci
alchickenwastes,canpr oduceet hanolf
rom
si
ngle-carbonsour cesi
ncludi
ngsy nthesi sgas,amixt
ure
ofcarbonmonoxi deandhy dr
ogen, thatcanbegener at
ed
fr
om thepar ti
al combust
ionofeitherf ossilfuel
sor
bi
omass.
:
-Clost
ri
dium but
yri
cum conv
ert
sgl
ycer
olt
o1,
3-
pr
opanediol
.
:
-Genesf rom Clostr
idi
um thermocell
um hav ebeen
i
nsertedintotr
ansgenicmi cetoall
owt heproducti
onof
endoglucanase.Theexperimentwasi ntendedtolear
n
moreabouthowt hedigestiv
ecapacityofmonogast r
ic
ani
mal scouldbei mproved.
:
-Nonpat hogenicst rai
nsofCl ostri
dium mayhel pi nthe
treatmentofdi seasessuchascancer .Researchshows
thatCl ostr
idium canselectiv
elyt argetcancercells.Some
strai
nscanent erandr epli
catewi thinsolidtumors.
Clostridi
um could, ther
efore,beusedt odelivert
her apeut
ic
proteinstot umour s.ThisuseofCl ostri
dium hasbeen
demonst r
atedinav ari
etyofpr ecli
nicalmodel s.
:
-Mi
xtur
esofCl
ost
ri
dium speci
es,
suchasCl
ost
ri
dium
beij
eri
ncki
i
, Cl
ost
ri
dium buty
ricum,andspeci
esfrom ot
her
generahavebeenshownt oproducebiohy
drogenfr
om
yeastwaste.