toxins dr. shivya

7/24/2019 Toxins Dr. Shivya

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BACTERIAL TOXINS


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The concept that pathogenic bacteria might elicit their harmfuleects in humans and animals by means of poisons elaboratedby them

William Edward van Heyningen 195!

19"


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Bacterial Virulence Factors


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#amage during infection occurs

#irect action of pathogen

Host response to infection

$ombination of both


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Invasion

Inhibition

ofphagocyto

sis

Colonization

Attachment

Toxinsand

enzymes

Virulence


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Host - parasite Interaction

Intracellular

EukaryoticCell

Receptor

Virulentacteria

!rokaryoticCell

!ili oradhesins


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!rokaryotic and Eukaryotic Interactions

Intracellular

EukaryoticCell

Receptor

Virulentacteria

!rokaryoticCell

C"#"$I%ATI"

Adherenceblockers

!ili oradhesins


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!rokaryotic and Eukaryotic Interactions

Intracellular

EukaryoticCell

Receptor

Virulentacteria

!rokaryoticCell

C"#"$I%ATI" I$VA&I"$

Adherenceblockers

!ili oradhesins


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Edwin %lebs &1'()*191(+ for staphylococci!

,obert %och &1')(*191+ for Vibriocholereae!

-nd .riedrich /oe0er &1'5*1915+ for

diphtheria bacillus!

These attempts failed for methodologicalreasons that are now understandable2

XINS


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3n 1'''! fortune smiled on Emile ,ou4 and-le4andre ersin2 6ince than microbial to4inshave been recogni7ed as the primary virulence

factor&s+ for a variety of pathogenic bacteria2


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Toxins86oluble substances that alter the normalmetabolism of host cells with deleteriouseects on the host8


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'b( Endotoxins are#I!"!"#)&ACC*ARI+E& that are a part of

outer membrane of cellwall of ram * vebacteria and arereleased when bacteriadie and cell wall brea:sapart


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E4oto4in Endoto4in

;rotein /ipopolysaccharide

Heat labile Heat stable

-ctively secreted by living cells 3ntegral part of cell wall released onlyon disruption of bacterial cell

Highly antigen Wea:ly antigenic

-ntito4in is formed against them -ntibody is formed

$onverted to to4oid by formaldehyde $annot to4oided

High potency /ow potency

;roduced mainly by ram ;ositiveve ?rganisms only


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Toxins Attacking ,IT

StaphylococcusBacillus cereusClostridium perfringensClostridium botulinum

Clostridium dicileE. ColiShigella dysenteriaeVibrio cholera

Vibrio mimicusVibrio parahaemolyticusPseudomonas aeruginosa

Aeromonas hydrophillia


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aphylococcal Enterotox!)R",E$IC T"-I$& They cause immunostimulation and nonspeci.c T/cell

proliferation0

/ittle is :nown about 6taphylococcal Enteroto4ins may have a direct eect on intestinal epithelium and on the

vagus nerve! causing stimulation of the emetic center and of guttransit

$ystine loop re@uired for proper conformation and which is

probably involved in the E1ETIC ACTIVIT)

Highly resistant! Heat 6table


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Sudden onset

Nausea Vomiting Diarrhea

Generally self limiting

disease


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A Activation of &econd1essenger

Escherichia. Coli

Clostridium botulinum

Bacillus cereus

Clostridium perfringes

=ibrio cholerae Bcholera to4in

;ainless watery diarrhea &,ice water stools+ #ehydration


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Cucleus


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Clostridium difcile

/arge molecular to4ins - D

< -ntibiotic associated colitis with

bloody diarrhea

;seudomembranous colitis


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$ytoto4ic

#isrupt the actin cytos:eleton and tight unctions

.luid accumulation and destruction of the intestinalepithelium2

,elease various inFammatory mediators from intestinal

epithelial

,ounding of the cells! membrane


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Associated with gastrointestinal disease

Chronic diarrhea in adults

Self-limited acute, severe disease in children

resembling shigellosis with blood and

leukocytes in the stool

3% carriage rate

Aeromonas


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Aerolysins2

$T?T?C3$li:e ETE$ and$holera To4in

$ytoto4in

;ore former


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Gsually self>limiting and of moderate severity2

Watery diarrhea! -bdominal cramps! Causea!=omiting! and Headache

Vibrio paraheamolyticus

T#H>,E/-TE#HE?/63C

&T,H+

THE,?6T- forming to4in! with the poresestimated at nm in diameter


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lostridium botulinum3ood poisoni

formed to4in in food 2

primary source of botulism was smo:ed blood sausages2

#r2Iustnus %erner posited that therewas something in the spoiledsausages that brought on thedisease> something he calledJwurstgiftK &erman for sausagepoison+

-bdominal painCauseafollowed by blurring of vision!diplopia! and diLculty in breathing2;ea:ing#eath due to respiratory failure


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abdominal cramps! shoc:! andbloodydiarrhoea2

ecrotising enteritis M Type $ N to4inec:! ermany! where it was called O#armbrand!Omeaning OPrebowelsO2

formation at plasma membranes of susceptible cells2ndothelial cells and induces vascular necrosis2

;ig>bel M e4cessive eating of pig eat

Clostridium perringesEnteroto4in by Type -

-ction li:e $T !ETE$ in diarrhea

' to hours after ingestion of contaminated food2

so causes


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Bacillus cereus Toxins

Emetic to4inJ$erulideK

Enteroto4in

Emesis

32;eriod of 25>5 hours

;reformed in foods

6timulates vagus nerve binding5HT( receptors

ulticomponent protein

-bdominal pain !watery diarrhea

32;eriod of '>1Q hours

.ormed in intestines of host

/ytic to4in! heamolytic!shows Fuid accumulation onligated rabbit ileal loop


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Shigella toxin


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oxins e4ecting 1usculoskeletal system

Clostridium. tetani

Clostridium. botulinum

Clostridium . perringens


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Clostridium tetani Tetanospasmin

?phisthotonus

/oc:ed aw


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stridium botulinum

/iberated during growth2


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W " ,elatively 6table

6ymmetric descending paralysis

?nset mar:ed by #3;/?;3- #ysphagia #ysarthria

#eath by respiratory paralysis

/iberated during growth2

6even types of to4ins &->+2

-ntigenic &light and heavy chain+2

Environmental survival2 &3nactivated by heat 1R$ for

min +2 /ethal doseS 1> g 2


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ns a4ecting the $ervous &ys


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ins a4ecting &kin 5 &oft Tiss

E4foliating to4in of Staphylococcus2

Bacillus.anthracis &$utaneous anthra4+2

-lpha to4in of Clostridium.perfringensetc.


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Exfoliating Toxin of&taphylococcus


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E4foliative to4ins &also :nown as JepidermolyticK to4ins+ are particularlyinteresting virulence factors of S. aureus2

E4tremely speciPc serine proteases recogni7e

#E6?6?-/$-#HE,3C6

.ragile! Fuid>Plledblisters

3EVER< 1A#AI&E< #ET*AR,)< A$+""R 3EE+I$,0

nly the s:in! but not the mucosa2

J K

Erythematous,ash

l h t i f Cl t idi i


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Hemolytic!

$ytoto4ic to ;/-TE/ET6 -C# /EG%?$TE6! -C# 3C$,E-6E6$-;3//-, ;E,E-


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;hospholipasec

J;erfringolysinK

#amage themembrane of cellsby attac:ing the

phopholipids

*aemolysis

ARAC*I+"$ICACI+ CA&CA+E

;rostaglandins /eu:otrienesThrombo4anes

!#ATE#ET A,,RE,ATE& "CC#=+E& #""+ VE&&E#&


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Bacillus anthracis


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?&=!ERA$TI,E$&@

&taphylococcal Enteroto4ins E4foliative to4ins To4ic>shoc: syndrome to4in

&treptococcal o ,roup a &treptococci pred0

S.pyogenes

TBelvestreptococcal pyrogenic e4oto4ins &6;Es+ -! $!>!6treptococcal superantigen &66-6treptococcal mitogenic e4oto4in &6E+ 1 and

$on ,roup A

o Streptococcus.equi

Too 1uch of a ,ood Thing

6ame T cell receptor =N chaindomains2Today! 1' dierent 6Eshave been described in theliterature

; i t i


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;yrogenic to4in! potent stimulation of the immune cell system H$ $lass 33 and T $ell receptor cells!

$oncentrations of 7D8 pgml suLcient to stimulate the Tlymphocytes in an uncontrolled manner resulting in fever! shoc:and death2

Toxic Shock Syndrome

Streptococcal toxic shock SyndromeKaasaki diseaseAc!te rhe!matic "e#erA!to imm!ne diseases

;ro>inFammatory cyto:ines! TC.>a

3/>1b 3/> feverand shoc:

To4ic shoc: syndrome &T66+


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To4ic shoc: syndrome &T66+hypotension! rash! des@uamation! fever and maor organinvolvement2

Acute rheumatic feverM 6moot et al showed that antibodies against


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Acute rheumatic feverM 6moot et al2 showed that antibodies against6;E> and 6;E>U were more common in convalescent sera from -,.patients compared to patients with pharyngitis

FaBasaki diseaseM 6everal investigators reported the selectivee4pansion of T cells bearing the =bV1 Tc,! which points towards a 6-g

involvement in the disease

Auto immune diseasesMno direct evidence of 6-g involvement6-gs could! under the right conditions! brea: the tolerance or

suppression of auto> reactive T cell clones and induce a state ofautoimmunity2

Evidence for this hypothesis came from an -C3-/ ?#E/ of multiplesclerosisM

a rapid relapse of the disease

Corynebacte


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3t is an acidic

!globular proteinwith a molecularweight mostrecently estimatedat Q! to Q(!

Corynebacterium

diphthriae

Clinical featuresl i 6 h


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alaise! 6ore throat! .ever A+*ERE$T ,RE) !&E=+" 1E1RA$E Casal ulcers! ?bstruction of laryn4 and lower airways! #iLculty in

swallowing /ead to yocarditis! ;eripheral neuritis! ;aralysis of limbs!


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!ertussis toxin $omple4 multisubunit to4in with

an -


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E4ploited to further basic :nowledge of cell biology or for medical

purposes2

oes can be friends too

C*"#ERA T"-I$

#AI#E/ T"-I$ "3 E0C"#I

0 !ERT=&&I&T"-I$wea:ening


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"T=#I$=1 T"-I$ T)!E A inectable selective muscle wea:eningagent19"s by -lan 6cott! a physician in $alifornia! who used it to treatstrabismus patients2 +isorder +ysfunction

$hronic headache Tension type headache

?veractive


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+ t ti


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+etection

$etection o" the patho%en

Nonh!man Experimental $ata "or Enterotoxins

3n vivo assays12 /igated intestinal loops

2 ;erfusion studies

(2 ?ral inoculation

)2 ,3T-,# ?#E/ MThereversible ileal tie adultrabbit diarrheal disease

mode

Tissue culture -ssaysM

Chinese hamsterovary 'C*"( and )/8

adrenal cells Cytotoxicity assay on

*e#a cell line0

& G663C $H-


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!ore 3ormers Aeromonas. hydrophila

Clostridium .perfringens

Escherichia coli

!isteria. monocytogenes

Staphylococcus. aureus

\>to4in Streptococcus pneumoniae

pneumolysin

Streptococcus pyogenesstreptolysin ?


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Corynebacterium diphtheriae"diphtheria to4in

E. Coli

Shigella dysenteriae

6higa to4ins ;

Pseudomonas aeruginosae4oto4in -

Inhibit protein synthes

A Activation of &econd


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A Activation of &econd1essenger

Escherichia. Coli

Bacillus anthracisBedema factor

Bordetella pertussis

#ermonecrotic to4in;ertussis to4in

Clostridium botulinum

Clostridium dicileto4in -to4in

toxins dr. shivya

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