toxins detail in brief..

1. TOXINS
Submittedto: Submittedby:
Dr MonikaAsthana Garima jain
Prashantsharma
M.Sc Biotchnology
First sem

2. OVERVIEW
 What are toxins?
 Types Of Toxins
 Exotoxin
 Type of Exotoxin
 Medical application
 Endotoxin
 Effects of endotoxin

3. WHAT ARE TOXINS?
 A toxin [Latin toxicum, poison] is a substance,
such as a metabolic product of the organism,
that alters the normal metabolism of host cells
with deleterious effects on the host.
 Toxins can be small molecules, peptides or
proteins that are capable of causing disease on
contact with or absorption by body
tissues interacting with
biological macromolecules such
as enzymes or cellular receptors. Toxins vary
greatly in their toxicity, ranging from usually
minor (such as a bee sting) to almost
immediately deadly (such as botulinum toxin).

4. TYPES OF TOXINS
Toxins produced by bacteria
can be divided
into two main categories:
1.Exotoxins
2.Endotoxins

5. EXOTOXINS VERSUS
ENDOTOXINS

6. EXOTOXINS
Exotoxins are soluble, heat-labile, proteins (a
few are enzymes) that usually are released
into the surroundings as the bacterial pathogen
grows.
Generally, exotoxins are produced by gram-
positive bacteria, although some gram-
negative bacteria also make exotoxins. Often
exotoxins may travel from the site of infection
to other body tissues or target cells in which
they exert their effects.

7. TYPE OF EXOTOXIN
Exotoxins can be grouped into four
types based on their structure
and physiological activities:
 AB Toxins
 Specific Host Site Exotoxins
 Membrane Disrupting
 Super Antigens

8. AB TOXINS
It is composed of two parts, where A is the
enzymes that disrupts some cell activity,
while B-binds surface receptors to bring A
into the host cell, e.g., botolinum and
tetanus toxin.

9. AB EXOTOXIN
TRANSPORT
MECHANISM

11. SPECIFIC HOST SITE
EXOTOXIN
It is categorized on the basis of
affected site
• neurotoxins (nerve tissue)
• enterotoxins (intestinal mucosa)
• cytotoxins (general tissues)

12. NEUROTOXIN
Neurotoxins usually are ingested as
preformed toxins that affect
the nervous system and indirectly cause
enteric (pertaining to
the small intestine) symptoms. Examples
include staphylococcal
enterotoxin B, Bacillus cereus emetic toxin
[Greek emetos, vomiting],
and botulinum toxin.

13. ENTEROTOXIN
The classic enterotoxin, cholera toxin
(choleragen), has been studied extensively.
It is anAB toxin. The B subunit is made of
five parts arranged as a donut-shaped ring.
The genes for this enterotoxigenicity are
encoded on a filamentous phage within
Vibrio cholera.

14. CYTOTOXIN
Cytotoxins have a specific toxic action
upon cells/tissues of special organs and
are named according to the type of
cell/tissue or organ for which they are
specific. Examples include nephrotoxin
(kidney), hepatotoxin (liver), and
cardiotoxin (heart).

15. MEMBRANE DISRUPTING
EXOTOXIN
 It lyses host cells by disrupting the integrity of the plasma
membrane.
 There are two subtypes of membrane disrupting exotoxins.
1.A channel-forming (pore-forming) type of exotoxin
The first, is a protein that binds to the cholesterol portion of
the host cell plasma membrane inserts itself into the
membrane, and forms a channel (pore). This causes the
cytoplasmic contents to leak out. Also, because the
osmolality of the cytoplasm is higher than the extracellular
fluid, this causes a sudden influx of water into the cell,
causing it to swell and rupture.

17. 2. A phospholipid-hydrolyzing phospholipase exotoxin
Phospholipases remove the charged head group from the
lipid portion of the phospholipids in the host-cell plasma
membrane. This destabilizes the membrane so that the cell
lyses and dies. One example of the pathogenesis caused by
phospholipases is observed in the disease gas gangrene. In
this disease, the Clostridium perfringens _-toxin almost
completely destroys the local population of white blood cells
(that are drawn in by inflammation to fight the infection)
through phospholipase activity.

19. SUPER ANTIGENS
They are the bacterial proteins that cause
proliferation of T-cells and release of
cytokines excessive cytokines can cause
fever, nausea, vomiting, diarrhoea, shock
and death (septic shock), e.g., toxic shock
syndrome (staphylococcus), e.g.,
enterotoxins: staphylococcal food
poisoning.

20. MEDICAL APPLICATION
OF EXOTOXIN
Vaccinations
Exotoxins have been used to produce vaccines. This process involves inactivating the
toxin, creating a toxoid that does not induce toxin-related illness and is well-tolerated. A
widely used toxoid vaccine is the DPT vaccine, which is usually administered in
multiple doses throughout childhood with adjuvants and boosters for long-term
immunity. DPT vaccine protects against pertussis, tetanus and diphtheria infections,
caused by the exotoxin-producing Bordetella pertussis, Clostridium
tetani and Corynebacterium diphtheriaerespectively.
Cancer treatment
As exotoxins are highly potent, there has been development in their application to
cancer treatment. Cancer cells can be eliminated without destroying normal cells like in
chemotherapy or radiation by attaching an antibody or receptor ligand to the exotoxin,
creating a recombinant toxin that is targeted to certain cells. The cancer cell is killed
once the toxin is internalized; for example, Pseudomonas exotoxin disrupts protein
synthesis after cellular uptake. Multiple versions of recombinant exotoxin A, secreted
by Pseudomonas aeruginosa, have entered clinical trials against tumor growth but have
yet to be approved by Food and Drug Administration. A recombinant diphtheria
exotoxin has been approved by the FDA for treatment of cutaneous T-cell lymphoma, an
immune system cancer. Further testing to improve clinical efficacy of treatment using
recombinant exotoxins continues.

21. ENDOTOXIN
 They are the part of the outer membrane portion of the cell
wall of gram negative bacteria, e.g., Lipopolysaccharide
(LPS) which is released when dead cells lyse in blood,
causes macrophages to release high levels of cytokines
resulting is chills, fever, weakness, aches, small blood
clots, tissue necrosis, shock and death.
 The toxic component of the LPS is the lipid portion, called lipid
A. Lipid A is not a single macromolecular structure but appears
to be a complex array of lipid residues. The lipid A component
exhibits all the properties associated with endotoxicity and
gram-negative bacteremia.

23. EFFECTS OF
ENDOTOXIN
 Fever is induced by interleukin-1, produced by the liver in
response to endotoxin, acting on the temperature-
regulating hypothalamus.
 The action of lipopolysaccharide on platelets and
activation of Hageman's factor causes disseminated
intravascular coagulation with ensuing ischaemic tissue
damage to various organs.
 Septic shock occurs during severe infections with Gram-
negative organisms when bacteria or lipopolysaccharide
enter the bloodstream.

25. THANK YOU