by SYEDA MARYAM

HASSNY
Definition
a toxin released by a living bacterial cell into its
surroundings.
• Secreted by bacteria
• Polypeptide in nature
• Genes are present on plasmid or bacteriophage
• They are among most toxic substance known
• They are good antigen and induce the synthesis of
protective antibodies called ANTITIOXIN
• Exotoxin + formaldehyde(or heat or acid) TOXOID
• Toxoid has high antigenic property but no toxicity
 MECHANISM of
ACTION of GRAM +tive
BACTERIA’s exotoxin
KEY POINTS

by SYEDA MARYAM HASSNY

Some examples of exotoxin
produced by gram +tive
bacteria
1 DIPHTHERIA TOXIN produced by CORYNEBACTERIUM DIPHTHERIA

2 TETANUS TOXIN(TENOSPSMIN) produced by CLOSTRIDIUM TETANI

3 BOTULINUM TOXIN produced by CLOSTRIDIUM BOTULINUM

4 Exotoxin produced by CLOSTRIDIUM DEFICILE

Exotoxin produced by CLOSRIDIUM PREFRENGIS and other species of

5 CLOSTRIDIA
6 Exotoxin of BACILUS ANTHRACUS

TOXIC SHOCK SYNDROME TOXIN(TSST) produced by S. AUREUS and some strains of S.

7 PYOGENS

8 STAPHYLOCCOCCAL ENTEROTOXIN

9 EXFOLIATIN produced by S. AUREUS

10 PANTON VALENTINE (PV)) LEUCOCIDIN produced by METHICILLIN RESISTANT STRAIN OF S.

AUREAUS

11 ERYTHROGENIC TOXIN produced by S. PYOGENS

 DIPHTHERIA TOXIN
1) produced by
CORYNEBACTERIUM
DIPHTHERIA
 by
• Inhibit protein synthesis ADP-Ribosylation of EF-2(elongation factor 2)
Which cause

DIPHTHERIA
Pseudomembrane form in throat

symptoms
myocarditis

• MECHANISM
toxin synthesized as single polypeptide non toxic (active site is masked)

Cleaved and modified

Active toxin
• ACTIVE TOXIN
2 active polypeptides fragment

Fragment A Fragment B
Derived from amino terminal Carboxyl end
of toxin
NAD Receptor for cell
membrane
catalyzes ADP-Ribose
transfer
for eukaryotic cell
Mediate transport
EF-2 Specificity for toxin due to
of fragment A into cell
Activity is very
DIPHTHAMIDE
As a result

potent
Modified histidine
Only present in EF-2
PSEUDOMONAS
Kill a cell in few Inactivates AERUGINOSA have
hours
same mode of action
Inhibit protein synthesis
 • An example of lysogenic conversion
Beta phage (lysogenic bacteriophage)

have
tox gene
infects

C. Diphtheria
causes

Diphtheria only lysogenic bacteria can cause

• Increase in Fe in medium increases tox gene repressors Tox gene

produced by bacteria transcription stops
 TETANUS TOXIN(TETNOSPASMIN)
2) produced by CLOSTRIDIUM
TETANI
• It’s a neurotoxin
• It’s encoded by plasmid DNA
• It prevents release of inhibitory neurotransmitter in muscle relaxation
• It contain two polypeptide units
• Toxin is released at peripheral wound travel through reteroaxonal
transport or blood stream towards anterior horn and interstitial
neuron
• It inhibits GABA and glycine which are inhibitory neurotransmitters
• It causes convulsive contraction of voluntary muscle e.g. Jaw and
neck muscles known as LOCK JAW
 TETANOSPASMIN

contain 2 polypeptide chains

Heavy chain Light chain

bind to ganglioside it’s a protease

degrades
in neuron membrane

proteins that
produce GABA and
Glysine
 BOTULINUM TOXIN produced
3) by CLOSTRIDIUM BOTULINUM
• It’s a neurotoxin that blocks release of many neurotransmitters e.g.
acetylcholine at synapse junction causes FLACCID PARALYSIS
• 1micro gram is fatal for human
• Toxin contain 2 polypeptide subunits
one unit bind to receptor site of neuron
other unit it’s a protease that degrade acetylcholine producing proteins
• The bacteria contain 6 stereotype i.e. from A F
• Stereotype A, B, E, F are medically most important to humans
• Stereotypes gene are encoded on PLASMID
TEMPLATE BACTERIOPHAGE
BACTERIAL CHROMOSOME
 EXOTOXIN PRODUCED BY CLOSTRIDIUM
4) PREFRENGIS AND OHER SPECIES OF
CLOSRIDIA
• C. Prefrengis produces multi toxin Gas Gangrene
• There are total 7 lethal factor + 5 enzymes
LECITHENASE It’s an ALPHA TOXIN
Heterogeneous hydrolyzes LECITHIN in
Not all are produced group cell membrane
by single species
destruction of
cell membrane
Hemolytic and
Necrotizing widespread cell death
activity PROTEASE
COLLAGENASE
HYALURONIDASE
DNASE
• Certain chains of C. Preferengis produces ENTEROTOXINS which act as
a SUPERANIGEN .
• This enterotoxin is similar to S. Aureus
• Enterotoxin causes WATTERY DIARRHEA
5) EXOTOXIN produced by CLOSTRIDIUM DEFICILE
• Clostridium deficile
Produces 2
exotoxins

Exotoxin A Exotoxin B
causes
Both are GLYCOSYL TRANSFERASES Is a cytotoxin
Watery
Diarrhea modify
Damage colonic
Signal transduction Rho GTPases Mucosa
protein which then
interferes
Signal transduction pathway Form PSEUDOMEMBRANE

Disaggregation of actin
PSEUDOMEMBRANOUS COLITIS filament of cytoskeleton

APOPTOSIS and cell death

6) EXOTOXIN OF
BACILIS
ANTHRACUS
• BACILUS ANTHRACUS
Produces 3 EXOTOXINS
Associates
EDEMA FACTOR LETHAL FACTOR PROTECTIVE ANTIGEN
with each
other
Is an Adenylate Is a Protease Bind with cell surface receptors
cyclase
cleaves
Result in Form pores in cell membrane
Phosphokinases controls
Increase of cAMP facilitates
Low conc.
in cell of phosph- signal EDEMA factor + LETHAL factor
kinases transduction to enter cell
Loss of Cl and water cause pahways
form cell Failure in cell growth Antibody against it causes
immune against disease
CELL DEATH Mechanism of
EDEMA in tissues Antibody’s working
Antibody blocks binding site
of PROTECTIVE ANTIGEN
on cell membrane
7) TSST (toxic shock syndrome toxin)
• Is a SUPPER ANTIGEN
• Produced primarily by S. pyogenes
• Binds directly to class 2 MHC protein on surface of
macrophages without intracellular processing and form
complex
interacts with T cell receptors of Helper T cell
activates T cells
release of large amount of IL-1, IL-2, and
TNF
produce sign and symptoms of
TOXIC SHOCK
8)SAPHYLOCOCCAL ENTEROTOXIN
• Is a super antigen
• Produced by S. aureus in contaminated food
• Act locally on lymphoid cell lining the small
intestine , because it is ingested
• Causes food poisoning within 1-6 hrs after ingestion
• Symptoms are vomiting and watery diarrhea
• Vomiting is caused by cytokines released from
lymphoid cells stimulating the enteric nervous
system , which activates vomiting center in brain
9) EXFOLIATIN
• Produced by S.AUREUS
• Also called EPIDERMOLYTIC TOXIN
• Is a protease
• Cleaves DESMOGLEIN (a protein in
desmosomes of the skin)
detachment of superficial skin
 PANTONE-VALENTINE
10) (leukocidin)
• Pore forming exotoxin
• Produced by METHICILLIN-RESISTANT
strains of S.AUREUS (MRSA)
• Destroys WBCs, skin and subcutaneous tissues
• It contains 2 subunits of toxin
assembles in cell membrane
form pores through cell membrane
cell content exit into extracellular space
11) ERYTHROGENIC TOXIN
• Produced by S.PYOGENES
• Causes rash characteristics of
SCARLET FEVER
• Mechanism of action similar to TSST
• Acts as SUPER ANTIGEN
• DNA that codes for it resides on
TEMPERATE BACTERIOPHAGE
• NONLYSOGENIC BACTERIA don’t cause
SCARLET FEVER although they can cause
PHARYNGITIS