Bacterial Toxins
Presented by :
M.Nouman
Msc –IV
Physical
Chemistry
What are toxins ?
• Biological poisons that assist in their ability to
invade and cause damage to tissues
• What is toxigenicity ?
• The ability of a pathogen to produce toxins to
cause damage to host cells is
called toxigenicity.
Bacterial Toxins :
• The toxins which are produced by micro-
organism like bacteria are called Bacterial
Toxins.
• They promote infections and diseases by directly
demaging host tissues and by disabling the
immune system.
Classification of Bacterial Toxins :
• They are classified as:
• 1-Endotoxin
• 2-Exotoxin
Endotoxins :
• Lipopolysaccharide (LPS) found on the
outer membrane of gram-negative bacteria is
called endotoxin .
• What is LPS ?
• It is a large molecule consisting of a lipid and
polysacchride composed of O-antigen outer core
and inner core joined by a covalent bond.
Figure :
Endotoxins:
• During infection and disease, gram-negative
bacterial pathogens release endotoxin either
when the cell dies, resulting in the disintegration
of the membrane, or when the bacterium
undergoes binary fission.
• The lipid component of endotoxin, lipid A, is
responsible for the toxic properties of the LPS
molecule. Lipid A is relatively conserved across
different genera of gram-negative bacteria;
therefore, the toxic properties of lipid A are
similar regardless of the gram-negative
pathogen.
Endotoxins :
• If the concentration of endotoxin in the body is
low, the inflammatory response may provide the
host an effective defense against infection; on
the other hand, high concentrations of endotoxin
in the blood can cause an excessive
inflammatory response, leading to a severe drop
in blood pressure, multi-organ failure, and
death.
How we detect Endotoxin in living
organism:
• A classic method of detecting endotoxin is by using
the Limulus amebocyte lysate (LAL) test.
• In this procedure, the blood cells (amebocytes) of
the horseshoe crab (Limulus polyphemus) is mixed
with a patient’s serum. The amebocytes will react to
the presence of any endotoxin.
• . This reaction can be observed either
chromogenically (color) or by looking for
coagulation (clotting reaction) to occur within the
serum.
Alternative method :
• An alternative method that has been used is an
enzyme-linked immunosorbent assay (ELISA)
that uses antibodies to detect the presence of
endotoxin.
Exotoxins :
• Exotoxins are protein molecules that are
produced by a wide variety of living pathogenic
bacteria.
• Although some gram-negative pathogens
produce exotoxins but the majority are produced
by gram-positive pathogens. Exotoxins differ
from endotoxin in several other key
characteristics.
Comparison of Endotoxin and
Exotoxins Produced by Bacteria :
Characteristic Endotoxin Exotoxin
Source Gram-negative bacteria
Gram-positive (primarily)
and gram-negative
bacteria
Composition
Lipid A component of
lipopolysaccharide
Protein
Comparison chart :
Effect on host
General systemic
symptoms of
inflammation and fever
Specific damage to
cells dependent upon
receptor-mediated
targeting of cells and
specific mechanisms
of action
Heat stability Heat stable
Most are heat labile, but
some are heat stable
LD50 High Low
Some Common Exotoxins and
Associated Bacterial Pathogens :
• The exotoxins can be grouped into three
categories based on their target:
• intracellular targeting.
• membrane disrupting.
• and superantigens.
Intracellular-targeting toxins :
Example Pathogen Mechanism and Disease
Cholera toxin Vibrio cholerae
Activation of adenylate
cyclase in intestinal cells,
causing increased levels
of cyclic adenosine
monophosphate (cAMP)
and secretion of fluids and
electrolytes out of cell,
causing diarrhea
Tetanus toxin Clostridium tetani
Inhibits the release of
inhibitory
neurotransmitters in the
central nervous system,
causing spastic paralysis
Intracellular-targeting toxins :
Botulinum toxin Clostridium botulinum
Inhibits release of the
neurotransmitter
acetylcholine from
neurons, resulting in
flaccid paralysis
Diphtheria toxin
Corynebacterium
diphtheriae
Inhibition of protein
synthesis, causing
cellular death
Membrane-disrupting toxins :
Alpha-toxin
Clostridium
perfringens
Phospholipases that
degrade cell
membrane
phospholipids,
disrupting membrane
function and killing the
cell
Phospholipase C
Pseudomonas
aeruginosa
Beta-toxin Staphylococcus aureus
Superantigens :
Toxic shock syndrome
toxin
Staphylococcus
aureus Stimulates excessive
activation of immune
system cells and
release of cytokines
(chemical mediators)
from immune system
cells. Life-threatening
fever, inflammation,
and shock are the
result.
Streptococcal mitogenic
exotoxin
Streptococcus pyogenes
Streptococcal pyrogenic
toxins
Streptococcus pyogenes
Diseases caused by bacterial toxins :
• There are many types of bacterial toxins that are
characterized by different modes of action.
• This section will focus on the mode of action of a
few toxins to show how they affect normal cell
functions and cause diseases:
Cholerae toxin :
• Cholerae toxin is a type of exotoxin produced by
the bacteria Vibrio cholerae. Also known as an
enterotoxin, the Cholera toxin is an AB toxin
which means that it consists of two main
subunits (A and B). The "B" subunit of the toxin
consists of 5 units and is responsible for
attachment to the cell of the host.
Cholerae toxins :
• On the other hand, the "A" subunit is the active
part of the toxin and is associated with the toxic
activities. Using the 5 units of the B subunit, the
toxin first binds to a glycolipid located on the
surface of the cell (cells of the intestinal
membrane) known as GM1
(monosialotetrahexosylganglioside). This
binding triggers endocytosis which causes the
toxin to be internalized into a vesicle and
transported to the Endoplasmic Reticulum.
Typhoid fever :
• Caused by salmonella typhi.
• Contaminated food and water or close contact
with an infacted person cause typhoid fever.
• Low grade fever ,dry cough and altered mental
status.
• It is still a serious health threat in the developing
world, especially for childern.
Hepatitis
• Hepatitis is inflammation of the liver.
Inflammation is swelling that happens when
tissues of the body are injured or infected. It can
damage your liver. This swelling and damage
can affect how well your liver
functions. Hepatitis can be an acute (short-
term) infection or a chronic (long-term)
infection.
What causes hepatitis?
• There are different types of hepatitis, with different causes:
• Viral hepatitis is the most common type. It is caused by one of
several viruses -- hepatitis viruses A, B, C, D, and E. In the
United States, A, B, and C are the most common.
• Alcoholic hepatitis is caused by heavy alcohol use
• Toxic hepatitis can be caused by certain poisons, chemicals,
medicines, or supplements
• Autoimmune hepatitis is a chronic type in which your body's
immune system attacks your liver. The cause is not known,
but genetics and your environment may play a role.
How is viral hepatitis spread?
• Hepatitis A and hepatitis E usually spread
through contact with food or water that was
contaminated with an infected person's stool.
You can also get hepatitis E by eating
undercooked pork, deer, or shellfish.
• Hepatitis B, hepatitis C, and hepatitis D spread
through contact with the blood of someone who
has the disease. Hepatitis B and D may also
spread through contact with other body fluids.
Who is at risk for hepatitis?
• The risks are different for the different types of
hepatitis.
• For example, with most of the viral types, your
risk is higher if you have unprotected sex. People
who drink a lot over long periods of time are at
risk for alcoholic hepatitis.
What are the symptoms of hepatitis?
• Some people with hepatitis do not have symptoms
and do not know they are infected. If you do have
symptoms, they may include
• Fever
• Fatigue
• Loss of appetite
• Nausea and/or vomiting
• Abdominal pain
• Dark urine
• Clay-colored bowel movements
• Joint pain
• Jaundice, yellowing of your skin and eyes
What other problems can hepatitis
cause?
• Chronic hepatitis can lead to complications such
as cirrhosis (scarring of the liver), liver failure,
and liver cancer. Early diagnosis and treatment
of chronic hepatitis may prevent these
complications.
• How is hepatitis diagnosed?
• To diagnose hepatitis, your health care provider
• Will ask about your symptoms and medical
history
How is hepatitis diagnosed?
• Will do a physical exam
• Will likely do blood tests, including tests for viral
hepatitis
• Might do imaging tests, such as
an ultrasound, CT scan, or MRI
• May need to do a liver biopsy to get a clear
diagnosis and check for liver damage
What are the treatments for
hepatitis?
• Treatment for hepatitis depends on which type you
have and whether it is acute or chronic. Acute viral
hepatitis often goes away on its own. To feel better,
you may just need to rest and get enough fluids. But
in some cases, it may be more serious. You might
even need treatment in a hospital.
• There are different medicines to treat the different
chronic types of hepatitis. Possible other treatments
may include surgery and other medical procedures.
People who have alcoholic hepatitis need to stop
drinking. If your chronic hepatitis leads to liver
failure or liver cancer, you may need a liver
transplant.
Can hepatitis be prevented?
• There are different ways to prevent or lower your
risk for hepatitis, depending on the type of
hepatitis.
• For example, not drinking too much alcohol can
prevent alcoholic hepatitis. There are vaccines to
prevent hepatitis A and B. Autoimmune
hepatitis cannot be prevented.
Toxoid :
• Toxoid is modified exotoxin. An exotoxin has
• two main properties :
• (1) toxicity, and
• (2) antigenicity.
• • In toxoid, the toxicity of the toxin is destroyed
• but its antigenicity is preserved. As such
• toxoids e.g. diphtheria toxoid, tetanus toxoid
• can be safely used for vaccines. Toxins can be
• converted to toxoid by different methods e.g.
• formalin treatment.
Toxoid :
How Our Body Eliminates Toxins ?
• 1. Liver :
• The liver has a critical role in the processing of
toxins, including some medications
• (such as acetaminophen) and alcohol.
• The liver contains many enzymes, which are special
proteins that can enable
• chemical reactions to take place in the body.
• Some of the enzymes in the liver are used for toxin
processing. Blood from the
• body flows through the liver where toxins in the
blood can be processed.
Liver :
• Some of the enzymes work to inactivate toxins to
keep them from damaging the
• body.
• Enzymes can also break down compounds in the
blood or modify them so that
• they stay dissolved and can then be excreted, via
the kidneys or other methods.
2. Kidneys :
• The kidneys are one of the primary ways in
which the body is able to eliminate toxins and
waste products from the blood.
• The kidney contains many small structures
called glomeruli, which essentially work to filter
substances (such as toxins and waste products)
out of the blood, where they are concentrated
into the urine, which is then excreted from the
body via the bladder and the urethra.
Kidneys:
• Some toxins don't get filtered out by the
glomeruli and are instead actively secreted by
the kidneys into the urine. Regardless, the
kidneys ability to secrete waste products and
toxins into the urine is one of the primary ways
in which toxins are eliminated from the body .
3. Sweat :
• Another way in which toxins can be eliminated
from the body is via sweat.
• • Some toxins and waste products in the blood
are able to diffuse into the sweat
• glands.
• • As a result, when the body excretes sweat (in
order to cool down), some toxins
• are excreted as well.
4. Gut:
• We all know that we get rid of most of our waste
through our bowels.
• If digestive system is not working properly, it can’t
get rid of unwanted waste and toxins properly.
• • Our body empties many toxins into our excrement,
but if it is sitting in the bowel too long (i.E. You are
constipated) — it can get reabsorbed and go through
our detox systems again — increasing their workload
and making them less effective.
The End ;;;;;;;;;;;;;;;;;

Bacterial toxins

  • 1.
    Bacterial Toxins Presented by: M.Nouman Msc –IV Physical Chemistry
  • 2.
    What are toxins? • Biological poisons that assist in their ability to invade and cause damage to tissues • What is toxigenicity ? • The ability of a pathogen to produce toxins to cause damage to host cells is called toxigenicity.
  • 3.
    Bacterial Toxins : •The toxins which are produced by micro- organism like bacteria are called Bacterial Toxins. • They promote infections and diseases by directly demaging host tissues and by disabling the immune system.
  • 4.
    Classification of BacterialToxins : • They are classified as: • 1-Endotoxin • 2-Exotoxin
  • 5.
    Endotoxins : • Lipopolysaccharide(LPS) found on the outer membrane of gram-negative bacteria is called endotoxin . • What is LPS ? • It is a large molecule consisting of a lipid and polysacchride composed of O-antigen outer core and inner core joined by a covalent bond.
  • 6.
  • 7.
    Endotoxins: • During infectionand disease, gram-negative bacterial pathogens release endotoxin either when the cell dies, resulting in the disintegration of the membrane, or when the bacterium undergoes binary fission. • The lipid component of endotoxin, lipid A, is responsible for the toxic properties of the LPS molecule. Lipid A is relatively conserved across different genera of gram-negative bacteria; therefore, the toxic properties of lipid A are similar regardless of the gram-negative pathogen.
  • 8.
    Endotoxins : • Ifthe concentration of endotoxin in the body is low, the inflammatory response may provide the host an effective defense against infection; on the other hand, high concentrations of endotoxin in the blood can cause an excessive inflammatory response, leading to a severe drop in blood pressure, multi-organ failure, and death.
  • 9.
    How we detectEndotoxin in living organism: • A classic method of detecting endotoxin is by using the Limulus amebocyte lysate (LAL) test. • In this procedure, the blood cells (amebocytes) of the horseshoe crab (Limulus polyphemus) is mixed with a patient’s serum. The amebocytes will react to the presence of any endotoxin. • . This reaction can be observed either chromogenically (color) or by looking for coagulation (clotting reaction) to occur within the serum.
  • 10.
    Alternative method : •An alternative method that has been used is an enzyme-linked immunosorbent assay (ELISA) that uses antibodies to detect the presence of endotoxin.
  • 11.
    Exotoxins : • Exotoxinsare protein molecules that are produced by a wide variety of living pathogenic bacteria. • Although some gram-negative pathogens produce exotoxins but the majority are produced by gram-positive pathogens. Exotoxins differ from endotoxin in several other key characteristics.
  • 12.
    Comparison of Endotoxinand Exotoxins Produced by Bacteria : Characteristic Endotoxin Exotoxin Source Gram-negative bacteria Gram-positive (primarily) and gram-negative bacteria Composition Lipid A component of lipopolysaccharide Protein
  • 13.
    Comparison chart : Effecton host General systemic symptoms of inflammation and fever Specific damage to cells dependent upon receptor-mediated targeting of cells and specific mechanisms of action Heat stability Heat stable Most are heat labile, but some are heat stable LD50 High Low
  • 14.
    Some Common Exotoxinsand Associated Bacterial Pathogens : • The exotoxins can be grouped into three categories based on their target: • intracellular targeting. • membrane disrupting. • and superantigens.
  • 15.
    Intracellular-targeting toxins : ExamplePathogen Mechanism and Disease Cholera toxin Vibrio cholerae Activation of adenylate cyclase in intestinal cells, causing increased levels of cyclic adenosine monophosphate (cAMP) and secretion of fluids and electrolytes out of cell, causing diarrhea Tetanus toxin Clostridium tetani Inhibits the release of inhibitory neurotransmitters in the central nervous system, causing spastic paralysis
  • 16.
    Intracellular-targeting toxins : Botulinumtoxin Clostridium botulinum Inhibits release of the neurotransmitter acetylcholine from neurons, resulting in flaccid paralysis Diphtheria toxin Corynebacterium diphtheriae Inhibition of protein synthesis, causing cellular death
  • 17.
    Membrane-disrupting toxins : Alpha-toxin Clostridium perfringens Phospholipasesthat degrade cell membrane phospholipids, disrupting membrane function and killing the cell Phospholipase C Pseudomonas aeruginosa Beta-toxin Staphylococcus aureus
  • 18.
    Superantigens : Toxic shocksyndrome toxin Staphylococcus aureus Stimulates excessive activation of immune system cells and release of cytokines (chemical mediators) from immune system cells. Life-threatening fever, inflammation, and shock are the result. Streptococcal mitogenic exotoxin Streptococcus pyogenes Streptococcal pyrogenic toxins Streptococcus pyogenes
  • 19.
    Diseases caused bybacterial toxins : • There are many types of bacterial toxins that are characterized by different modes of action. • This section will focus on the mode of action of a few toxins to show how they affect normal cell functions and cause diseases:
  • 20.
    Cholerae toxin : •Cholerae toxin is a type of exotoxin produced by the bacteria Vibrio cholerae. Also known as an enterotoxin, the Cholera toxin is an AB toxin which means that it consists of two main subunits (A and B). The "B" subunit of the toxin consists of 5 units and is responsible for attachment to the cell of the host.
  • 21.
    Cholerae toxins : •On the other hand, the "A" subunit is the active part of the toxin and is associated with the toxic activities. Using the 5 units of the B subunit, the toxin first binds to a glycolipid located on the surface of the cell (cells of the intestinal membrane) known as GM1 (monosialotetrahexosylganglioside). This binding triggers endocytosis which causes the toxin to be internalized into a vesicle and transported to the Endoplasmic Reticulum.
  • 22.
    Typhoid fever : •Caused by salmonella typhi. • Contaminated food and water or close contact with an infacted person cause typhoid fever. • Low grade fever ,dry cough and altered mental status. • It is still a serious health threat in the developing world, especially for childern.
  • 23.
    Hepatitis • Hepatitis isinflammation of the liver. Inflammation is swelling that happens when tissues of the body are injured or infected. It can damage your liver. This swelling and damage can affect how well your liver functions. Hepatitis can be an acute (short- term) infection or a chronic (long-term) infection.
  • 24.
    What causes hepatitis? •There are different types of hepatitis, with different causes: • Viral hepatitis is the most common type. It is caused by one of several viruses -- hepatitis viruses A, B, C, D, and E. In the United States, A, B, and C are the most common. • Alcoholic hepatitis is caused by heavy alcohol use • Toxic hepatitis can be caused by certain poisons, chemicals, medicines, or supplements • Autoimmune hepatitis is a chronic type in which your body's immune system attacks your liver. The cause is not known, but genetics and your environment may play a role.
  • 25.
    How is viralhepatitis spread? • Hepatitis A and hepatitis E usually spread through contact with food or water that was contaminated with an infected person's stool. You can also get hepatitis E by eating undercooked pork, deer, or shellfish. • Hepatitis B, hepatitis C, and hepatitis D spread through contact with the blood of someone who has the disease. Hepatitis B and D may also spread through contact with other body fluids.
  • 26.
    Who is atrisk for hepatitis? • The risks are different for the different types of hepatitis. • For example, with most of the viral types, your risk is higher if you have unprotected sex. People who drink a lot over long periods of time are at risk for alcoholic hepatitis.
  • 27.
    What are thesymptoms of hepatitis? • Some people with hepatitis do not have symptoms and do not know they are infected. If you do have symptoms, they may include • Fever • Fatigue • Loss of appetite • Nausea and/or vomiting • Abdominal pain • Dark urine • Clay-colored bowel movements • Joint pain • Jaundice, yellowing of your skin and eyes
  • 28.
    What other problemscan hepatitis cause? • Chronic hepatitis can lead to complications such as cirrhosis (scarring of the liver), liver failure, and liver cancer. Early diagnosis and treatment of chronic hepatitis may prevent these complications. • How is hepatitis diagnosed? • To diagnose hepatitis, your health care provider • Will ask about your symptoms and medical history
  • 29.
    How is hepatitisdiagnosed? • Will do a physical exam • Will likely do blood tests, including tests for viral hepatitis • Might do imaging tests, such as an ultrasound, CT scan, or MRI • May need to do a liver biopsy to get a clear diagnosis and check for liver damage
  • 30.
    What are thetreatments for hepatitis? • Treatment for hepatitis depends on which type you have and whether it is acute or chronic. Acute viral hepatitis often goes away on its own. To feel better, you may just need to rest and get enough fluids. But in some cases, it may be more serious. You might even need treatment in a hospital. • There are different medicines to treat the different chronic types of hepatitis. Possible other treatments may include surgery and other medical procedures. People who have alcoholic hepatitis need to stop drinking. If your chronic hepatitis leads to liver failure or liver cancer, you may need a liver transplant.
  • 31.
    Can hepatitis beprevented? • There are different ways to prevent or lower your risk for hepatitis, depending on the type of hepatitis. • For example, not drinking too much alcohol can prevent alcoholic hepatitis. There are vaccines to prevent hepatitis A and B. Autoimmune hepatitis cannot be prevented.
  • 32.
    Toxoid : • Toxoidis modified exotoxin. An exotoxin has • two main properties : • (1) toxicity, and • (2) antigenicity. • • In toxoid, the toxicity of the toxin is destroyed • but its antigenicity is preserved. As such • toxoids e.g. diphtheria toxoid, tetanus toxoid • can be safely used for vaccines. Toxins can be • converted to toxoid by different methods e.g. • formalin treatment.
  • 33.
  • 34.
    How Our BodyEliminates Toxins ? • 1. Liver : • The liver has a critical role in the processing of toxins, including some medications • (such as acetaminophen) and alcohol. • The liver contains many enzymes, which are special proteins that can enable • chemical reactions to take place in the body. • Some of the enzymes in the liver are used for toxin processing. Blood from the • body flows through the liver where toxins in the blood can be processed.
  • 35.
    Liver : • Someof the enzymes work to inactivate toxins to keep them from damaging the • body. • Enzymes can also break down compounds in the blood or modify them so that • they stay dissolved and can then be excreted, via the kidneys or other methods.
  • 36.
    2. Kidneys : •The kidneys are one of the primary ways in which the body is able to eliminate toxins and waste products from the blood. • The kidney contains many small structures called glomeruli, which essentially work to filter substances (such as toxins and waste products) out of the blood, where they are concentrated into the urine, which is then excreted from the body via the bladder and the urethra.
  • 37.
    Kidneys: • Some toxinsdon't get filtered out by the glomeruli and are instead actively secreted by the kidneys into the urine. Regardless, the kidneys ability to secrete waste products and toxins into the urine is one of the primary ways in which toxins are eliminated from the body .
  • 38.
    3. Sweat : •Another way in which toxins can be eliminated from the body is via sweat. • • Some toxins and waste products in the blood are able to diffuse into the sweat • glands. • • As a result, when the body excretes sweat (in order to cool down), some toxins • are excreted as well.
  • 39.
    4. Gut: • Weall know that we get rid of most of our waste through our bowels. • If digestive system is not working properly, it can’t get rid of unwanted waste and toxins properly. • • Our body empties many toxins into our excrement, but if it is sitting in the bowel too long (i.E. You are constipated) — it can get reabsorbed and go through our detox systems again — increasing their workload and making them less effective.
  • 40.