INTERNATIONAL UNIVERSITY – VNU HCMC

School of Biotechnology – Major in Food Technology

TOXICOLOGY AND FOOD SAFETY

MICROBIAL TOXIN: BACTERIAL TOXIN

Group 5
Submitted to: Dr. Nguyen Vu Hong Ha

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Members:
Nguyễn Thị Cẩm Nhi
BTFTIU17041
Trương Mỹ Tuyết
BTFTIU17089
Nguyễn Đông Nghi
BTFTIU17090
Nguyễn Thị Thu Hà

BTFTIU17044
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 I. INTRODUCTION

II. EXOTOXIN

III. ENDOTOXIN
OUTLINE
IV. SUMMARIZE

V. REFERENCES
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 INTRODUCTION

 What is toxin?

Metabolic Damage host tissues

product
Specific substance Damage the host
Pathogen Microorganism Disable the immune system

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 INTRODUCTION
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Produced by Molds Mycotoxin

MICROBIAL
TOXIN

Produced by Bacteria Bacterial Toxin

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 INTRODUCTION

Bacterial Toxin
Lipopolysaccharides (LPS) Soluble proteins

ENDOTOXINS EXOTOXINS

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 Exotoxins are diverse, they
have different Structures and
different modes of action.
 Some will form pores in the
host cell plasma membrane,
 some will bind receptors,
 others will be internalized by
the host cell.
 Proteins in nature, secreted from a
living bacterium and released upon
bacterial lysis.
 Most commonly from G+ bacteria,
some by G- bacteria.
EXOTOXINS
Causing damage physiologically or
pathologically to the host by destroying cells
or disrupting normal cellular metabolism.
 The production of the toxin is generally
specific to a particular bacterial species that
produces the disease associated with the
toxin.
For examples, only Clostridium tetani
produces tetanus toxin and only
Corynebacterium diphtheriae produces the
diphtheria toxin.
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 CHARACTERISTICS OF EXOTOXIN
Some protein toxins have very specific cytotoxic activity.

For example: tetanus and botulinum toxins attack only neurons ( neurotoxins)
 Some toxins (as produced by staphylococci, streptococci, clostridia, etc.) have fairly broad
cytotoxic activity  cause nonspecific death of various types of cells or damage to tissues,
eventually resulting in necrosis.
Usually the site of damage caused by an exotoxin indicates the location for activity of that
toxin.
For example: enterotoxins (intestinal mucosa), neurotoxins (nerve tissue), cytotoxins (general
tissues), leukocidin or hemolysin (blood cells)

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 CHARACTERISTICS OF EXOTOXIN
 Utilized as invasins because they act locally to promote bacterial invasion.

Examples are extracellular enzymes (collagenase, hyaluronidase and streptokinase) that

degrade tissue matrices or fibrin, allowing the bacteria to spread.
 Usually controlled by extrachromosomal genes such as plasmids and phage gene.
 Not all exotoxins are necessarily produced to harm humans.

Some may be designed to play a role in bacterial physiology, such as resisting bacteriophages,
regulating cellular function, or quorum sensing.
Other toxins may be produced primarily to target protozoa, insects, and smaller animals and
harming human cells becomes an accidental side effect.
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 CHARACTERISTICS OF EXOTOXINS
 Highly toxic and fatal to animals in very small doses.
 Heat labile—toxicity inactivated over 60°C

 Highly antigenic — stimulate formation of antitoxin (antibody) 

neutralizes the toxin.
 Passive immunity by injection of Antitoxin, anti-serum containing
antibodies.
 Inherently unstable (inactivated by heat or chemical treatment) 
Converted to toxoid (nontoxic but antigenic that used to immunize)
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 Classification
by
mode of action
on animal cells

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 TYPE I TOXINS
Type I toxins bind to a receptor on the cell surface
and stimulate intracellular signaling pathways.
For examples:
(1) the Escherichia coli heat-stable toxin (H-ST)
(2) the superantigenic toxins (SAGs) from
Staphylococcus aureus and Streptococcus
pyogenes.
(3) the Bacteroides fragilis enterotoxin (BFT) or
fragilysin

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 TYPE II TOXINS

Membrane dramge toxins (cytolysins) or Pore-

forming toxins.
• “prepore” = monomers + receptor
• Structural modification of monomer
hydrophobic domains (black)
• Forming a pore
• Leading to a leakage of the cell cytoplasmic
content..

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 TYPE II TOXINS

• For examples:
(1) toxins forming small pores (SPFTs): alpha toxin and the Panton–
Valentine leukocidin from S. aureus .
(2) toxins forming large pores (LPFTs): streptolysin O from Streptococcus
pyogenes.
(3) RTX toxins or E. coli alpha hemolysin
(4) insecticidal toxins: Bacillus thuringiensis toxins kill insects by forming
pores into cell membranes of the insect midgut.  formulated into
commercial insecticides.

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 TYPE III TOXINS
Toxins Injecting an Active Subunit Inside the Host
Cells: The ‘A–B Toxin’ Family.
A–B toxins are not only the most elaborated
toxins on the structural viewpoint but also the
most powerful ones. Focused on:
(1) the mode of action of the subunit A of the
toxin in the cytosol
(2) the mechanisms by which the subunit A is
introduced into the cytosol.

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 TYPE III TOXINS
(a) AB Diptheria: Block cell protein synthesis  kill the cells.
(b) A+5B Cholera: Dehydration and electrolyte imbalance  watery diarrhea
(c) 2A+B Anthrax (edema toxin and lethal toxin)  proteins to enter the cell
and disrupt cellular function  leads to cellular death (synergistic effect)

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 DISEASE
DISEASE BACTERIUM TYPE OF MECHANISM SYMPTOMS
EXOTOXIN

Botulism Clostridium A-B Neurotoxin prevents the Weakness ~ 7.5% risk

botulinum transmission of nerve Blurred vision of death
impulse, flaccid paralysis Feeling tired
results Trouble speaking

Tetanus Clostridium A-B Neurotoxin blocks nerve Vomiting 25-90%

tetani impulse to muscle Fever risk of
relaxation pathway Aches death
=> uncontrollable muscle Diarrhea
contractions

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 DISEASE BACTERIUM TYPE OF MECHANISM SYMPTOMS
EXOTOXIN
Food Staphylococcus Superantigen Enterotoxin causes Fever --~ 10%
poisoning aureus secretion of fluids Sweating risk of
and electrolytes Trouble death
=> diarrhea swallowing
High blood
pressure
Fast heart rate

Toxic Staphylococcus Superantigen Toxins causes Inflammation

shock aureus secretion of fluids Fever
syndrome and electrolytes shock
(TSS) from capillaries that
decrease blood
volume and low

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 ENDOTOXINS

LPS: LipoPolySaccharide
Outer membrane present in the cell wall of gram negative
bacteria.  
Function: protect membrane from chemical attack
Gram- negative bacteria are Escherichia coli, Proteus,
Pseudomonas, Enterobacter and Klebsiella.

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 ENDOTOXINS
 Structure:
 Differentiates bacteria
 Nontoxic
 The O polysaccharide is
hydrophilic and may allow
diffusion or delivery of the toxic
lipid in the hydrophilic
environment.
 The O-polysaccharide is
antigenic
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 ENDOTOXINS
 Structure:
 A hydrophobic lipid section
 Responsible for the toxic
properties
 The toxic properties of lipid
A are similar regardless of
the gram-negative
pathogen. 
 Lipid A triggers the immune
system’s inflammatory
response
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 CHARACTERISTICS OF ENDOTOXIN
Lipopolysaccharides are heat stable endotoxins (not destroyed above 60oC
for hours)
Endotoxins are weakly antigenic and not converted to toxoid
The release of LPS from bacteria takes place after death and lysis of the cell,
or release during metabolism of bacteria

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 PATHWAY
 Natural defense cell recognize the bacteria as
foreign by its O-antigen
 Defense cells degrade bacteria cell cell lyse 
release toxin
 LPS bind to LPS-binding protein  from bound LPS
 Bound LPS bind to receptor molecule CD14
 Promote the ability of the pattern recognition
receptor TLR-4 release cytokines include
interleukin 1, 6,8;TNF alpha-tumor necrosis factor-
alpha; PAF, platelet-activating factor
 These cytokines cause some inflammatory
response

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 ENDOTOXIN LEVEL
• Low: <0.4 EU/ml
• Intermediate: 0.4 - 0.59 EU/ml
• High: ≥0.6 EU/ml
 EU=Unit of measurement for endotoxin activity: 10 EU/mL = 1.0 ng/mL

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 FEVER
Prostaglidin
Maintain Hypothalamus
homeostasis
“thermal setting”
Interleukin-1

Elevate body temperature

Fever
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 ALLERGY

MAST CELL
O - antigen
• Mast cells are present in blood
vessels
• Rich in histamine
• LPS attach to its receptor
 Mast cells degranulation
 Histamines
 Allergic response

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 ENDOTOXIN SHOCK

 Systemic release of inflammatory mediators  Endotoxin shock

 Endotoxin interacts with inflammatory cells, platelets, and
vascular endothelium  cytokines (tumor necrosis factor and
interleukins, and lipid mediators)  endotoxemia  tachypnea,
vomiting, mucoid bloody diarrhea, weakness, fever, and chills

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 SEPTIC SHOCK

 Septic shock is defined as sepsis associated with hypotension and

perfusion abnormalities despite the provision of adequate fluid
(volume) resuscitation.
 Systemic vasodilation (hypotension):
 Endotoxin damage tissue  interact with mediators  Prostaglandins,
leukotriene, lipid mediator  mast cell  histamine, leukotriene,
prostaglandins, proteases, and chemotactic agent.

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 SEPTIC SHOCK

 Systemic vasodilation (hypotension):
 High histamine, leukotriene, prostaglandins => dilating the blood vessels
=> Increase the vascular permeability => decrease vascular resistance =>
vasodilate the blood vessel
 Chemotactic agent as signal immune system => pull white blood cell out
 C3 and C5 => activate endothelial cell dilating => increase immune
response => more white blood cells come out
 Cytokines:
 IL-1 and TNF-alpha increase => affect hypothalamus => prostaglandins => Fever
 IL-6 => liver => acute phase reactive protein

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 SEPTIC SHOCK

 Dissenminated intravascular coagulation:

 Plasminogen (enzyme)  plasma  break up the clots  fibrinolysis 
carried out by Tissue Plasminogen Activator (TPA)
 Endothelial cell  increase Plasminogen activator inhibitor type 1 (PAI-
1)  decrease plasma  cannot break up the clots  Ischemia 
thrombus develops  decrease blood flow

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SEPTIC SHOCK

Tissue factor T
Prothrombin Thrombin

Fibrinogen Fibrin
+Platelets

HEMOSTASIS

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 DISSENMINATED INTRAVASCULAR COAGULATION
(DIC)
Produce clot Clot breaking
Tissue factor is increased in response to cytokines

Cytokine NORMAL
Tissue factor
Thrombin T
Prothrombin
T T
Fibrinogen Fibrin
Platelets
DIC
Hemostasis 32
 DISSENMINATED INTRAVASCULAR COAGULATION
(DIC)

 Blocks the flow of blood through the capillaries

 Hypovolemia decreases the volume of circulating
blood hypotension  vasodilation  decreases
the pressure needed to deliver blood throughout
the body  Diminished myocardial contractility
 Widespread endothelial injury and activation 
system leukocyte adhesion and diffuse alveolar
capillary damage in the lung
 Loss of gas exchange in the lungs (acute
respiratory distress syndrome or ARDS)

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 DISSENMINATED INTRAVASCULAR COAGULATION
(DIC)

 Deep vein thrombosis

 As clotting factors and platelets are used
up, bleeding may occur

 blood in the urine, blood in the stool, or

bleeding into the skin.

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 SUMMARY

Table shows the differences between Endotoxin and Exotoxin:

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 PROPEETIES ENDOTOXIN EXOTOXIN

Chemical Lipopolysaccharide (LPS) Protein, often with 2 components (A

compositions
Kind of bacteria Gram negative (E.coli, Proteus,
Pseudomonas, Enterobacter)
Locaction Part of outer membrane
Released when the cell lyses
and B)
Both Gram positive and Gram
negative ( most is Gram positive)
Excreted outside the living cell

Toxicity Weakly toxic and rarely fatal Highly toxic and often fatal
(>100 microgram) (1 microgram)
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 PROPERTY ENDOTOXIN EXOTOXIN
Heat stability Most are heat sensitive and Heat stable
inactivated at 60-80oC

Symptoms General: fever, diarrhea, vomitting Specific disease: either cytotoxin,

enterotoxin or neurotoxin with
specific action on cell or tissues

Disease example Fever, blood coagulation, Tetanus, botulism,..

hypotension, septic shock

Vaccine Vaccine available (formed from

toxoids)

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 REFERENCES
Aktories K and Barbieri JT (2005) Bacterial cytotoxins: Targeting eukaryotic switches. Nature Reviews Microbiology 3(5): 397–410.
Alouf JE (2000) Bacterial protein toxins. An overview. Methods in Molecular Biology 145: 1–26.
Alouf, J.E., Popoff, M.R. (Eds.), 2006. Bacterial Protein Toxins, third ed. Academic Press, New York.
Cossart, P., Boquet, P., Normark, S., Rappuoli, R. (Eds.), 2005. Cellular Microbiology, second ed. ASM Press, Washington, DC.
http://faculty.ccbcmd.edu/courses/bio141/lecguide/unit1/prostruct/lpsharm.html
https://open.oregonstate.education/microbiology/chapter/17-5inflammation-and-fever/
Hotchkiss, R. S., Moldawer, L. L., Opal, S. M., Reinhart, K., Turnbull, I. R., & Vincent, J. L. (2016). Sepsis and septic shock
Adamik, B., Zielinski, S., Smiechowicz, J., & Kübler, A. (2015). Endotoxin elimination in patients with septic shock: an observation
study. Archivum immunologiae et therapiae experimentalis, 63(6), 475-483.
Trzeciak, Stephen (2008). Critical Care Medicine || Septic Shock. , (), 439–452
Ronco, C.; Piccinni, P.; Rosner, M.H. (2010). [Contributions to Nephrology] Endotoxemia and Endotoxin Shock Volume 167 ||
Endotoxins and Other Sepsis Triggers. , (), 14–24. 
Elizabeth M. Hardie; Kris Kruse-Elliott (1990). Endotoxic Shock : Part I: A Review of Causes. , 4(5), 258–266. 38
THANKS FOR YOUR ATTENTION

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