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Bacterial Toxins
Sources
Sources and reservoirs : soil, mud, water and intestinal tracts of animals
Foods:
• Improperly canned low-acid foods(green beans, corn, beets, asparagus,
mushrooms, spinach)
• Smoked fish and fermented food
• Improperly home cured hams
• Flavoured oil and oil infusions
 In 1993, FDA required acidification of such preparations to prevent the
growth of Clostridia.
Classification
1. On the basis of activity
Emetic toxins (i.e., Bacillus cereus)
Neurotoxins (botulinum toxin)
Enterotoxins
Cytotoxic enterotoxins
Cytotonic enterotoxins
2. On the basis of origin
Exotoxins are synthesized and released
(usually by Gram-positive bacteria) and
are not an integral part of the organism,
but may enhance its virulence Eg.
diptheria, tetani toxin
Endotoxin is generally a
lipopolysaccharide membrane constituent
released from a dead or dying Gram-
negative bacteria, these toxins are
nonspecific and stimulate inflammatory
Bacillus cereus
• Gram-positive
• Spore forming rod
• Aerobe
• Cause foodborne illness causing severe nausea, vomiting and diarrhoea
• Reservoirs: soil and dust.
Toxins
Emetic thermostable toxin Diarrheagenic thermolabile toxin
• Can survive at 126°C
for 90 min
• Small cyclic peptide
that acts on 5-HT3
receptors stimulating
vagus afferent nerve
• Serotypes: 1,3 and 8
• Can survive at 56
°C for 20 min
• associated with
diarrhoea and
gastrointestinal pain
• Serotypes:
1,2,6,8,10 and 19
Foods associated
• Emetic form: boiled and fried rice
• Diarrheal form: wider occurrence and
may be found in meats, stews, pudding,
sauces, dairy products, vegetable dishes,
soups, and meatloaf
Confirmed by the isolation of more than 105 B. cereus organisms
per gram from epidemiologically implicated food, but such testing
is often not done because the illness is relatively harmless and
usually self-limiting.
Diagnosis
Most emetic patients recover within 6–24
hours
Prognosis
Botulinum toxin (Neurotoxin)
• Produced by the Clostridium
botulinum
• Anaerobic
• Gram-positive
• Spore-forming rod
• Commonly found on plants, in soil,
water and the intestinal tracts of
animals
• Food botulism rarely causes illness
• Botulinum toxin:
• Toxins A,B,E and F in humans
• C. butyricum (Type E only) and C.baratti ;toxins C and D in animals
• Type G has not caused any human cases
• Symptoms:
• Drooping eyelids
• Double vision
• Inability to make facial expression
• Difficulty in swallowing
LD50 - 1.3–
2.1 ng/kg IV or IM and
10–13 ng/kg when
inhaled
Clostridium perfringens (Enterotoxin)
C. perfringens is classified into five types (A–E) depending
upon their ability to produce alpha, beta, epsilon, and eta toxin
• Primary Reservoir: intestinal tract of warm-blooded animals
(including humans)
• Food poisoning associated with consumption of roasted meat
that has been contaminated with intestinal contents at
slaughter, followed by roasting and inadequate storage.
• Foods associated with C. perfringens poisoning include
cooked meat or poultry, gravy, stew, and meat pies. C.
perfringens is also associated with the production of another
11 toxins, including those associated with gas gangrene.
Staphylococcus aureus
• Dangerous and versatile pathogen that can cause a
multitude of different diseases
• Exoproteins: toxic shock syndrome toxin-1 (TSST-1), the
exfoliative toxins ETA and ETB, leukociden and the
staphylococcal enterotoxins
• Sources: nose and throat discharges, hands and skin,
infected cuts, wounds, burns, boils, pimples, and faeces
• Primary reservoirs: anterior nares of humans
• Other reservoirs:
• Mastitic udders of cows (contamination of
unpasteurized milk)
• Bruised tissues of poultry
• Food contaminated after cooking
• Keeping food items at room temperature for several
hours
• Foods associated:
• poultry and dressing; sauces and gravy;
• Cream filled pastry, potatoes, ham, poultry, fish
salads, milk, cheese and generally high protein
Staphylococcal enterotoxins (SE)
• Emesis is produced as the result of stimulation of the putative SE
receptors in the abdominal viscera, following which is a cascade of
inflammatory mediator release
• Properties:
• ability to cause emesis and gastroenteritis in primates
• Superantigenicity
• intermediate resistance to heat and pepsin digestion
Toxic shock syndrome toxin-1 (TSST-1)
• Characterized by low blood
pressure, fever, diarrhoea, an
extensive skin rash, and shedding
of the skin.
• TSS results from the massive
overproduction of cytokines by T
cells induced by the TSST-1.
• TSST-1 binds both class II MHC
receptors and T-cell receptors,
stimulating T-cell responses.
• TSST-1 is a superantigen.
Cyanotoxins are generally grouped according to their site of action into
hepatotoxins, neurotoxins, and dermatotoxins
• hepatotoxins are the microcystins, which are produced by a number of
cyanobacterial species
• including species in the Microcystis, Nostoc, Oscillatoria, and Anabaena genera
• produce liver damage through binding to and inhibiting serine/threonine
phosphatases, leading to hyperphosphorylation of proteins and disruption of
hepatocyte structure and function
• Death is caused by hemorrhagic shock which follows the breakdown of liver
circulation and accumulation of blood in the liver
• At lower chronic exposures, microcystins lead to chronic inflammation.
• BMAA, another neurotoxic cyanotoxin, stimulates glutamate receptors and has been
hypothesized to be a causative agent in lytico-bodig, the neurodegenerative disease
endemic to Guam.
• Saxitoxin, a sodium channel blocker, is also produced by some cyanobacteria (as well
as by some dinoflagellates)
• Cyanotoxins have been determined to be responsible for toxicity to both wildlife and
to domestic livestock.
• Growth of cyanobacteria has been observed to reduce growth of green algae as well as
aquatic plants such as duckweed and elodea
Toxin Disease Symptoms
Diphtheria toxin
Corynebacterium
diphtheriae
Diphtheria Begins with sour throat and fever, painful
swallowing, difficulty in breathing,
formation of grey pseudo membrane
covering the tonsils
Tetanus toxin
Clostridium tetani
Tetanus Tetanic spasms,
fever, sweating, headache, trouble
swallowing, high blood pressure, and
a fast heart rate
Cholera toxin
Vibrio cholerae
Cholera watery diarrhoea leading to
severe dehydration and electrolyte
imbalance.
Pertussis toxin
Bordetella pertussis
Whooping cough initial symptoms similar to common
cold with followed by weeks of severe
coughing fits.
Other bacterial toxins
Toxins can function in multiple ways,
by inhibiting protein synthesis (diphtheria toxin),
• activating second messenger pathways (Bacillus anthracis edema factor or cholera
toxin),
• activating immune responses (S. aureus superantigens),
• damaging cell membranes (E. coli hemolysin),
• by general action of metalloprotease activity (Clostridium tetani tetanus toxin).
Applications of bacterial toxins
• Bacterial toxins are proteins capable of achieving multiple remarkable tasks. They
function as autonomous molecular devices, targeting specific cells in an organism,
punching holes in their membranes, or modifying intracellular components.
• Bacterial toxins, which are primarily harmful, are also being used for the cure of
cancer, killing of mosquito larvae.
MYCOTOXIN
INTRODUCTION
 A mycotoxin is a toxic secondary metabolite which is produced by organisms of
fungi kingdom , commonly known as molds.
 One mold species may produced many different mycotoxins, and the same
mycotoxin may be produced by several species.
 Mycotoxins are associated with human disease and cause acute and chronic effect.
Factors affecting the production of
mycotoxin
 Physical factors
Temperature between 40 C to 90
Humidity more then 70%
Moisture (22- 23%)
 Chemical factors
Nutritional factors, including inorganic ions
Use of fungistats
 Biological Factors
Strain of organism
Microbial detoxification
Mechanism
 Bind to DNA and RNA
 Oxidative stress
 Alter protein synthesis and function
 Alter cell membrane function and transport
 Alter apoptosis
Types of mycotoxin
 Aflatoxin : B1, B2 , G1and G2
 Ochratoxin : Ochratoxin A , Ochratoxin B ,Ochratoxin C
 Citrinin
 Ergot Alkaloids
 Patulin
 Fusarium : Fumonisins , Trichothecenes, Zearalenone.
 T-2 toxin, Deoxyniba-lenol
 Deoxynival- lenol(DON)
Mushroom toxins
 Toadstools are non-edible
 Amanita caesarea (Caesaer’s mushroom)
 Amanita Palloides (Death cap)
 Amanita muscaria (Fly agaric)
 contain amatoxins, heat-stable peptides
 amatoxins is the inhibition of RNA polymerase,
 leading to a blockade of protein synthesis.
Health effects of mycotoxins
 Mycotoxins ae believed to be among the most potent known carcinogen.
 Effect ranges from immediate toxic responses and immunosuppression to
potential long-term teratogenic, estrogenic and estrogenic.
 Food poisoning
 Inhibition of protein synthesis
 Increase of tryptophan in blood and brain
 Nausea , vomiting
 Abdominal pain , diarrhoea
 Breast enlargement in boys
 immunosuppressor
Application of mycotoxins
 Medical application
Trichothecenes are known to possess antileukaemic activity.
Zearalenone derivatives have been considered as potential treatment for menopausal
syndrome in women.
 Agricultural applcations
Derivatives of zearalenone as growth promoter n sheep and cattle ; other have been
used as herbicides and insecticides.
PLANT TOXINS
INTRODUCTION
• Scientist have been aware of existing secondary plant products for many years. These are
basically chemicals which are manufactured by plant but do not seem to play any role in
metabolism, growth, and other life processes.
• These products of plant are toxic or repellent to herbivores and microbes and help defending
plant producing them. They are evolved as defence mechanism.
• First secondary plant product to be isolated and studied is “ MORPHINE’’ in early 1800s .
-> The classes of secondary metabolites are :-
1. Alkaloids
2. Terpenes and Terpenoids
3. Glycosides
PLANT ALKALOID
• “Alkaloid” refers to diverse group of chemicals of botanical origin which contain heterocyclic
Nitrogen and are generally derived from amino acid.
• Examples of alkaloids are :- cocaine , caffeine , nicotine , morphine , atropine , capsaicin ,
strychnine.
• CAFFEINE
• Caffeine along with its relatives theophylline and theobromine is a xanthine alkaloid and its
physiological effects have been known for centuries: were first deduced from observations of
effects of coffee berries on livestock.
• Xanthines are found in multiple plants including coffee plants , where they probably act to
discourage pests from feeding on plant and inhibit germination of other plant in the
surrounding soil.
• The three xanthines are also found in tea plant [camellia sinensis] and theobroma cacao, the
plant whose seeds are used to produce chocolate.
PHARMACOLOGICAL ACTIONS
• Caffeine is responsible for BLOCKADE OF ADENOSINE RECEPTORS which play a role in
modulating release of several neurotransmitters {including dopamine , acetyl choline ,
glutamate, GABA}
• Adenosine receptors are G – Protein coupled receptors and come in four subtypes. Caffeine
has highest affinity for A1 and A2 receptors; activation of which leads to suppression of
neuronal activity.
• Ubiquity of adenosine receptors in brain leads to diverse effects of caffeine to increase
alertness, improve mood , decrease reaction times.
• Caffeine also increases anxiety.
• Chronic consumption is linked to reduction in risk for development of dementia and
adenosine receptor blockade.
• Discontinuation of chronic caffeine intake :- withdrawl symptoms will be seen. This is due to
the adenosine receptors upregulation and increase in number that occur in response to
chronic induced adenosine receptors blockade.
• Once exposure ceases there is a period of time before compensatory downregulation
restores receptor balance. In that interim overabundance of adenosine receptors can lead to
other effects i.e increase in cerebral vasodilation which produces classic caffeine withdrawl
headache.
• CAPSAICIN
• It is another alkaloid which is found in plants of genus capsicum , defence against herbivores.
• Capsaicin is an agonist at a receptor called transient receptor potential vanilloid 1 receptor
(TRPV1).
• This receptor is found in variety of areas of mammalian brain and play a role in heat and pain
pathways .
• Binding of capsaicin to receptors:- induces refractory state , it is used in analgesic
preparations. ( although used in combination with other anasthetics to block any unpleasant
irritant sensation.
TERPENES AND TERPENOIDS
• Defense mechanism used by plant is production of “latex” a complex fluid released upon
injury containing terpenes and terpenoids.
• POINSETTIA – A common holiday plant rocketed into notority on the basis of 1944 book
reporting unconfirmed death of child followed by ingetion of leaf.
• Terpenoids in poinsettias have the potential to irritate human skin – CONTACT DERMITIS
PLANT GLYCOSIDES
• Amygdalin [in almond] and Linamarin [in cassava plant] are classified as cynogenic
glycosides. These compounds serve defensive functions, in that if plant is attacked then;
cynogenic glycoside is broken to release Hydrogen Cyanide.
• Still it is seen that Cassava root is major source of food in Africa but it must be processed in
order to remove all the traces of glycosides.
• Digoxin and Digitalis are steroidal glycosides found in fox glove. These are basically cardiac
glycosides and are Na+/K+ ATPase blockers and have been used to treat variety of
cardiovascular conditions due to effects on myocardial contraction and conductibility.
OTHER IRRITANTS
• Dieffenbachia species are examples of plants capable of causing irritation. Colloquially k/a
“dumb cane”, these if ingested can produce pair of swelling of mouth , tongue, and oral
cavity. This effect has long been attributed to the crystals of Calcium Oxalate (Raphide) which
are found in plants.
• Raphides are found in Daffodils and also along with variety of alkaloids produce “Daffodils
itch” which is common complaint of florists
• Sap of stinging nettles (Urtica species) contains a complex mixture of chemicals including
formic acid, acetylcholine, and histamine which its stinging hairs (trichomes) can inject into
organisms unfortunate enough to brush up against it.
1) Dieffenbachia plant
2) Stinging nettles of urtica
species
POISON IVY AND ALLERGIC CONTACT
DERMATIS
• Allergic contact dermatis involves interaction
of plant constituents with immune system to
produce an allergic reaction. The plant
widely known for this is POISON IVY, (genus-
toxicodendron)
• Common In North America ,these are
responsible for millions of allergic contact
dermatis cases per year.
• Urushiol is found in roots, leaves and stems
of toxicodendron spp. Upon contact with the
chemical a rash type develops within a day
or two of exposure which will resolve within
2-3 weeks.
TOXINS OF
INVERTEBRATES
CNIDARIA
Chironex fleckeri(box jellies)
• Long poisonous tentacles
• Nematocyst contains venom injected
either to prey ,defense or predate.
• Shoot out spine-tipped,coiled tubule
and delivers toxin.
• Venom composition:-
proteins(cytolytic)and cardiotoxic
components.
• Significant toxins:- Toxin -1 (CfTX-1)and Toxin-2 (CfTX-2) share
features with pore forming toxins.
• Mechanism of action :- Pore formation and effect on ion
channels
• LD50 values of toxins of jellyfish is between 30 and 300
micrograms per kg.
• Symptoms:-painful sting,cardiovascular complication,
hypertension, hypotension, arrhythmias,respiratory arrest.
Physalia physalis(Portuguese man ‘o’war)
• Sting extremely pain rather than lethal.
• Colony made of 4 types of zooids:-
• 1-polyp(dactylozooids – form tentacles 20 m long)
• 2-polyp(pneumatophore-gas filled member used to swim
.
• 3-polyp(for feeding) and 4-polyp(for reproduction).
Nematocyst conatains- enzymes,catalytic
peptides,neurotoxins.
Symptoms-severe pain,allergies,fever,shock,cardiac
problems.
Arthropodes
Class –Arachnida
Australian funnel web spiders
• Belong to Atrax genus ,large ,dangerous to
humans .
• Venom toxic to Na+ ion channels 》Massive
release of neurotransmitters 》hypertension》
edema》intracranial hypertension and death
of prey.
• Ca+,,Na+,K+channel blockers.
Class –Arachnida and Diplopoda
Brown recluse spiders (Loxosceles
reclusa)
• Necrotic venom rich in –sphingomyelinase,
• protease,phosphplipase and
hyaluronidase.
• Symptoms-
itching,swelling,oedema,necrotic
area formed.
Millipedes
• Segmented body,release toxins
when pressed.
• Body fluids contains
toxins(cyanide & quonones)
• Symptome-mucous membrane
inflammation,blackish brown
hyperpigmentation lesion.
Scorpions –the deadliest
The death stalker (Leiurus quinquestriatus)
• It is one of the most venomous scorpion.
• Venom is a mixture of deadly neuro toxins.
• Person will experience extreme
pain,convulsions, paralysis and even death
due to cardiac and respiratory failure.
Mollusks
Cone snails (Conus spp.)
• Venome contains a group of peptides called
conotoxins.
• Conotoxins mechanism of action-rich in
• disulfude bonds ,target Na+,Ca+,K+channels,nicotine
and Ach receptors
• Have high specificity for binding to targets only in 1
type of prey.
• Clinical importance :- Ziconotide in clinical trials for
use in pain management.
Blue-ringed octopus(Hapalochlaena
maculosa)
• Uses toxins for prey capturing and defense.
• Main component of venom is Tetradotxin(TTX).
• TTX also found in skin of octupus.
• Mechanism of action:-TTX blocks the generation
of action potential and blocks Na+ channels .
• LD50 of tetradotoxin in mice is around 300
micrograms per kg.
• Symptoms:-weakness,numbness,ataxia,higher
doses cause paralysis,respiratory arrest and
parenthesis.
Puffer fish secretes
Tetrodotoxin is a sodium
channel blocker.
Stingrays possess barbed and serrated spines which
also feature toxin-producing cells.
These cells sustain damage when the spine is thrust
into target tissue, and some of the toxin enters the
wound.
Neotropical poison dart frogs ( Dendrobates spp. and Phyllobates spp.). These small, brightly colored
frogs secrete alkaloids including batrachotoxin, which locks sodium channels in an open position.
Toad secretions can contain epinephrine, norepinephrine, GABA, and
serotonin, bufotenine, a hallucinogenic compound. Some new tissues, contain
tetrodotoxin.
• Snake venom is produced in venom glands in the upper jaws and
is delivered through ducts to the base of enlarged teeth (fangs).
• These teeth often contain grooves, which may be open or closed,
and through which the venom flows and is delivered upon biting.
Viperidae, the fangs are basically hollow.
• Actual injection of venom is produced by action of a muscle on
the venom gland and is under the control of the snake.
• Snakes typically deliver doses of venom that may be in the range
of 100 times the lethal dose for their prey.
Snake venoms the non-enzymatic polypeptides
• Dendrotoxins (from mamba venoms) which are potassium channel blockers
• Cardiotoxins (from cobra venoms) which produce red cell hemolysis
• Erabutoxins (from sea snake venom)Cobratoxins which block the nicotinic
acetylcholine receptor
• Crotamine (from rattlesnake venom) which acts on sodium channels.
Antivenom
• Monovalent (specific for one species) or polyvalent (active against several species,
typically from the same region). Patient may suffer a hypersensitivity reaction
Gila monster
Mexican beaded lizard cobra
mambas
Rattle Snake

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Bacterial and Fungal Toxins: Sources, Mechanisms and Effects

  • 1.
  • 3. Sources Sources and reservoirs : soil, mud, water and intestinal tracts of animals Foods: • Improperly canned low-acid foods(green beans, corn, beets, asparagus, mushrooms, spinach) • Smoked fish and fermented food • Improperly home cured hams • Flavoured oil and oil infusions  In 1993, FDA required acidification of such preparations to prevent the growth of Clostridia.
  • 4. Classification 1. On the basis of activity Emetic toxins (i.e., Bacillus cereus) Neurotoxins (botulinum toxin) Enterotoxins Cytotoxic enterotoxins Cytotonic enterotoxins
  • 5. 2. On the basis of origin Exotoxins are synthesized and released (usually by Gram-positive bacteria) and are not an integral part of the organism, but may enhance its virulence Eg. diptheria, tetani toxin Endotoxin is generally a lipopolysaccharide membrane constituent released from a dead or dying Gram- negative bacteria, these toxins are nonspecific and stimulate inflammatory
  • 6. Bacillus cereus • Gram-positive • Spore forming rod • Aerobe • Cause foodborne illness causing severe nausea, vomiting and diarrhoea • Reservoirs: soil and dust. Toxins Emetic thermostable toxin Diarrheagenic thermolabile toxin • Can survive at 126°C for 90 min • Small cyclic peptide that acts on 5-HT3 receptors stimulating vagus afferent nerve • Serotypes: 1,3 and 8 • Can survive at 56 °C for 20 min • associated with diarrhoea and gastrointestinal pain • Serotypes: 1,2,6,8,10 and 19
  • 7. Foods associated • Emetic form: boiled and fried rice • Diarrheal form: wider occurrence and may be found in meats, stews, pudding, sauces, dairy products, vegetable dishes, soups, and meatloaf Confirmed by the isolation of more than 105 B. cereus organisms per gram from epidemiologically implicated food, but such testing is often not done because the illness is relatively harmless and usually self-limiting. Diagnosis Most emetic patients recover within 6–24 hours Prognosis
  • 8. Botulinum toxin (Neurotoxin) • Produced by the Clostridium botulinum • Anaerobic • Gram-positive • Spore-forming rod • Commonly found on plants, in soil, water and the intestinal tracts of animals • Food botulism rarely causes illness • Botulinum toxin: • Toxins A,B,E and F in humans • C. butyricum (Type E only) and C.baratti ;toxins C and D in animals • Type G has not caused any human cases • Symptoms: • Drooping eyelids • Double vision • Inability to make facial expression • Difficulty in swallowing LD50 - 1.3– 2.1 ng/kg IV or IM and 10–13 ng/kg when inhaled
  • 9. Clostridium perfringens (Enterotoxin) C. perfringens is classified into five types (A–E) depending upon their ability to produce alpha, beta, epsilon, and eta toxin • Primary Reservoir: intestinal tract of warm-blooded animals (including humans) • Food poisoning associated with consumption of roasted meat that has been contaminated with intestinal contents at slaughter, followed by roasting and inadequate storage. • Foods associated with C. perfringens poisoning include cooked meat or poultry, gravy, stew, and meat pies. C. perfringens is also associated with the production of another 11 toxins, including those associated with gas gangrene.
  • 10. Staphylococcus aureus • Dangerous and versatile pathogen that can cause a multitude of different diseases • Exoproteins: toxic shock syndrome toxin-1 (TSST-1), the exfoliative toxins ETA and ETB, leukociden and the staphylococcal enterotoxins • Sources: nose and throat discharges, hands and skin, infected cuts, wounds, burns, boils, pimples, and faeces • Primary reservoirs: anterior nares of humans • Other reservoirs: • Mastitic udders of cows (contamination of unpasteurized milk) • Bruised tissues of poultry • Food contaminated after cooking • Keeping food items at room temperature for several hours • Foods associated: • poultry and dressing; sauces and gravy; • Cream filled pastry, potatoes, ham, poultry, fish salads, milk, cheese and generally high protein
  • 11. Staphylococcal enterotoxins (SE) • Emesis is produced as the result of stimulation of the putative SE receptors in the abdominal viscera, following which is a cascade of inflammatory mediator release • Properties: • ability to cause emesis and gastroenteritis in primates • Superantigenicity • intermediate resistance to heat and pepsin digestion
  • 12. Toxic shock syndrome toxin-1 (TSST-1) • Characterized by low blood pressure, fever, diarrhoea, an extensive skin rash, and shedding of the skin. • TSS results from the massive overproduction of cytokines by T cells induced by the TSST-1. • TSST-1 binds both class II MHC receptors and T-cell receptors, stimulating T-cell responses. • TSST-1 is a superantigen.
  • 13. Cyanotoxins are generally grouped according to their site of action into hepatotoxins, neurotoxins, and dermatotoxins • hepatotoxins are the microcystins, which are produced by a number of cyanobacterial species • including species in the Microcystis, Nostoc, Oscillatoria, and Anabaena genera • produce liver damage through binding to and inhibiting serine/threonine phosphatases, leading to hyperphosphorylation of proteins and disruption of hepatocyte structure and function • Death is caused by hemorrhagic shock which follows the breakdown of liver circulation and accumulation of blood in the liver • At lower chronic exposures, microcystins lead to chronic inflammation.
  • 14. • BMAA, another neurotoxic cyanotoxin, stimulates glutamate receptors and has been hypothesized to be a causative agent in lytico-bodig, the neurodegenerative disease endemic to Guam. • Saxitoxin, a sodium channel blocker, is also produced by some cyanobacteria (as well as by some dinoflagellates) • Cyanotoxins have been determined to be responsible for toxicity to both wildlife and to domestic livestock. • Growth of cyanobacteria has been observed to reduce growth of green algae as well as aquatic plants such as duckweed and elodea
  • 15. Toxin Disease Symptoms Diphtheria toxin Corynebacterium diphtheriae Diphtheria Begins with sour throat and fever, painful swallowing, difficulty in breathing, formation of grey pseudo membrane covering the tonsils Tetanus toxin Clostridium tetani Tetanus Tetanic spasms, fever, sweating, headache, trouble swallowing, high blood pressure, and a fast heart rate Cholera toxin Vibrio cholerae Cholera watery diarrhoea leading to severe dehydration and electrolyte imbalance. Pertussis toxin Bordetella pertussis Whooping cough initial symptoms similar to common cold with followed by weeks of severe coughing fits. Other bacterial toxins
  • 16. Toxins can function in multiple ways, by inhibiting protein synthesis (diphtheria toxin), • activating second messenger pathways (Bacillus anthracis edema factor or cholera toxin), • activating immune responses (S. aureus superantigens), • damaging cell membranes (E. coli hemolysin), • by general action of metalloprotease activity (Clostridium tetani tetanus toxin).
  • 17. Applications of bacterial toxins • Bacterial toxins are proteins capable of achieving multiple remarkable tasks. They function as autonomous molecular devices, targeting specific cells in an organism, punching holes in their membranes, or modifying intracellular components. • Bacterial toxins, which are primarily harmful, are also being used for the cure of cancer, killing of mosquito larvae.
  • 19. INTRODUCTION  A mycotoxin is a toxic secondary metabolite which is produced by organisms of fungi kingdom , commonly known as molds.  One mold species may produced many different mycotoxins, and the same mycotoxin may be produced by several species.  Mycotoxins are associated with human disease and cause acute and chronic effect.
  • 20.
  • 21. Factors affecting the production of mycotoxin  Physical factors Temperature between 40 C to 90 Humidity more then 70% Moisture (22- 23%)  Chemical factors Nutritional factors, including inorganic ions Use of fungistats  Biological Factors Strain of organism Microbial detoxification
  • 22. Mechanism  Bind to DNA and RNA  Oxidative stress  Alter protein synthesis and function  Alter cell membrane function and transport  Alter apoptosis
  • 23.
  • 24. Types of mycotoxin  Aflatoxin : B1, B2 , G1and G2  Ochratoxin : Ochratoxin A , Ochratoxin B ,Ochratoxin C  Citrinin  Ergot Alkaloids  Patulin  Fusarium : Fumonisins , Trichothecenes, Zearalenone.  T-2 toxin, Deoxyniba-lenol  Deoxynival- lenol(DON)
  • 25. Mushroom toxins  Toadstools are non-edible  Amanita caesarea (Caesaer’s mushroom)  Amanita Palloides (Death cap)  Amanita muscaria (Fly agaric)  contain amatoxins, heat-stable peptides  amatoxins is the inhibition of RNA polymerase,  leading to a blockade of protein synthesis.
  • 26. Health effects of mycotoxins  Mycotoxins ae believed to be among the most potent known carcinogen.  Effect ranges from immediate toxic responses and immunosuppression to potential long-term teratogenic, estrogenic and estrogenic.  Food poisoning  Inhibition of protein synthesis  Increase of tryptophan in blood and brain  Nausea , vomiting  Abdominal pain , diarrhoea  Breast enlargement in boys  immunosuppressor
  • 27. Application of mycotoxins  Medical application Trichothecenes are known to possess antileukaemic activity. Zearalenone derivatives have been considered as potential treatment for menopausal syndrome in women.  Agricultural applcations Derivatives of zearalenone as growth promoter n sheep and cattle ; other have been used as herbicides and insecticides.
  • 29. INTRODUCTION • Scientist have been aware of existing secondary plant products for many years. These are basically chemicals which are manufactured by plant but do not seem to play any role in metabolism, growth, and other life processes. • These products of plant are toxic or repellent to herbivores and microbes and help defending plant producing them. They are evolved as defence mechanism. • First secondary plant product to be isolated and studied is “ MORPHINE’’ in early 1800s . -> The classes of secondary metabolites are :- 1. Alkaloids 2. Terpenes and Terpenoids 3. Glycosides
  • 30. PLANT ALKALOID • “Alkaloid” refers to diverse group of chemicals of botanical origin which contain heterocyclic Nitrogen and are generally derived from amino acid. • Examples of alkaloids are :- cocaine , caffeine , nicotine , morphine , atropine , capsaicin , strychnine. • CAFFEINE • Caffeine along with its relatives theophylline and theobromine is a xanthine alkaloid and its physiological effects have been known for centuries: were first deduced from observations of effects of coffee berries on livestock. • Xanthines are found in multiple plants including coffee plants , where they probably act to discourage pests from feeding on plant and inhibit germination of other plant in the surrounding soil. • The three xanthines are also found in tea plant [camellia sinensis] and theobroma cacao, the plant whose seeds are used to produce chocolate.
  • 31.
  • 32. PHARMACOLOGICAL ACTIONS • Caffeine is responsible for BLOCKADE OF ADENOSINE RECEPTORS which play a role in modulating release of several neurotransmitters {including dopamine , acetyl choline , glutamate, GABA} • Adenosine receptors are G – Protein coupled receptors and come in four subtypes. Caffeine has highest affinity for A1 and A2 receptors; activation of which leads to suppression of neuronal activity. • Ubiquity of adenosine receptors in brain leads to diverse effects of caffeine to increase alertness, improve mood , decrease reaction times. • Caffeine also increases anxiety. • Chronic consumption is linked to reduction in risk for development of dementia and adenosine receptor blockade. • Discontinuation of chronic caffeine intake :- withdrawl symptoms will be seen. This is due to the adenosine receptors upregulation and increase in number that occur in response to chronic induced adenosine receptors blockade. • Once exposure ceases there is a period of time before compensatory downregulation restores receptor balance. In that interim overabundance of adenosine receptors can lead to other effects i.e increase in cerebral vasodilation which produces classic caffeine withdrawl headache.
  • 33. • CAPSAICIN • It is another alkaloid which is found in plants of genus capsicum , defence against herbivores. • Capsaicin is an agonist at a receptor called transient receptor potential vanilloid 1 receptor (TRPV1). • This receptor is found in variety of areas of mammalian brain and play a role in heat and pain pathways . • Binding of capsaicin to receptors:- induces refractory state , it is used in analgesic preparations. ( although used in combination with other anasthetics to block any unpleasant irritant sensation.
  • 34. TERPENES AND TERPENOIDS • Defense mechanism used by plant is production of “latex” a complex fluid released upon injury containing terpenes and terpenoids. • POINSETTIA – A common holiday plant rocketed into notority on the basis of 1944 book reporting unconfirmed death of child followed by ingetion of leaf. • Terpenoids in poinsettias have the potential to irritate human skin – CONTACT DERMITIS
  • 35. PLANT GLYCOSIDES • Amygdalin [in almond] and Linamarin [in cassava plant] are classified as cynogenic glycosides. These compounds serve defensive functions, in that if plant is attacked then; cynogenic glycoside is broken to release Hydrogen Cyanide. • Still it is seen that Cassava root is major source of food in Africa but it must be processed in order to remove all the traces of glycosides. • Digoxin and Digitalis are steroidal glycosides found in fox glove. These are basically cardiac glycosides and are Na+/K+ ATPase blockers and have been used to treat variety of cardiovascular conditions due to effects on myocardial contraction and conductibility.
  • 36. OTHER IRRITANTS • Dieffenbachia species are examples of plants capable of causing irritation. Colloquially k/a “dumb cane”, these if ingested can produce pair of swelling of mouth , tongue, and oral cavity. This effect has long been attributed to the crystals of Calcium Oxalate (Raphide) which are found in plants. • Raphides are found in Daffodils and also along with variety of alkaloids produce “Daffodils itch” which is common complaint of florists • Sap of stinging nettles (Urtica species) contains a complex mixture of chemicals including formic acid, acetylcholine, and histamine which its stinging hairs (trichomes) can inject into organisms unfortunate enough to brush up against it.
  • 37. 1) Dieffenbachia plant 2) Stinging nettles of urtica species
  • 38. POISON IVY AND ALLERGIC CONTACT DERMATIS • Allergic contact dermatis involves interaction of plant constituents with immune system to produce an allergic reaction. The plant widely known for this is POISON IVY, (genus- toxicodendron) • Common In North America ,these are responsible for millions of allergic contact dermatis cases per year. • Urushiol is found in roots, leaves and stems of toxicodendron spp. Upon contact with the chemical a rash type develops within a day or two of exposure which will resolve within 2-3 weeks.
  • 40. CNIDARIA Chironex fleckeri(box jellies) • Long poisonous tentacles • Nematocyst contains venom injected either to prey ,defense or predate. • Shoot out spine-tipped,coiled tubule and delivers toxin. • Venom composition:- proteins(cytolytic)and cardiotoxic components.
  • 41. • Significant toxins:- Toxin -1 (CfTX-1)and Toxin-2 (CfTX-2) share features with pore forming toxins. • Mechanism of action :- Pore formation and effect on ion channels • LD50 values of toxins of jellyfish is between 30 and 300 micrograms per kg. • Symptoms:-painful sting,cardiovascular complication, hypertension, hypotension, arrhythmias,respiratory arrest.
  • 42. Physalia physalis(Portuguese man ‘o’war) • Sting extremely pain rather than lethal. • Colony made of 4 types of zooids:- • 1-polyp(dactylozooids – form tentacles 20 m long) • 2-polyp(pneumatophore-gas filled member used to swim . • 3-polyp(for feeding) and 4-polyp(for reproduction). Nematocyst conatains- enzymes,catalytic peptides,neurotoxins. Symptoms-severe pain,allergies,fever,shock,cardiac problems.
  • 43. Arthropodes Class –Arachnida Australian funnel web spiders • Belong to Atrax genus ,large ,dangerous to humans . • Venom toxic to Na+ ion channels 》Massive release of neurotransmitters 》hypertension》 edema》intracranial hypertension and death of prey. • Ca+,,Na+,K+channel blockers.
  • 44. Class –Arachnida and Diplopoda Brown recluse spiders (Loxosceles reclusa) • Necrotic venom rich in –sphingomyelinase, • protease,phosphplipase and hyaluronidase. • Symptoms- itching,swelling,oedema,necrotic area formed. Millipedes • Segmented body,release toxins when pressed. • Body fluids contains toxins(cyanide & quonones) • Symptome-mucous membrane inflammation,blackish brown hyperpigmentation lesion.
  • 45. Scorpions –the deadliest The death stalker (Leiurus quinquestriatus) • It is one of the most venomous scorpion. • Venom is a mixture of deadly neuro toxins. • Person will experience extreme pain,convulsions, paralysis and even death due to cardiac and respiratory failure.
  • 46. Mollusks Cone snails (Conus spp.) • Venome contains a group of peptides called conotoxins. • Conotoxins mechanism of action-rich in • disulfude bonds ,target Na+,Ca+,K+channels,nicotine and Ach receptors • Have high specificity for binding to targets only in 1 type of prey. • Clinical importance :- Ziconotide in clinical trials for use in pain management.
  • 47. Blue-ringed octopus(Hapalochlaena maculosa) • Uses toxins for prey capturing and defense. • Main component of venom is Tetradotxin(TTX). • TTX also found in skin of octupus. • Mechanism of action:-TTX blocks the generation of action potential and blocks Na+ channels . • LD50 of tetradotoxin in mice is around 300 micrograms per kg. • Symptoms:-weakness,numbness,ataxia,higher doses cause paralysis,respiratory arrest and parenthesis.
  • 48. Puffer fish secretes Tetrodotoxin is a sodium channel blocker. Stingrays possess barbed and serrated spines which also feature toxin-producing cells. These cells sustain damage when the spine is thrust into target tissue, and some of the toxin enters the wound.
  • 49. Neotropical poison dart frogs ( Dendrobates spp. and Phyllobates spp.). These small, brightly colored frogs secrete alkaloids including batrachotoxin, which locks sodium channels in an open position. Toad secretions can contain epinephrine, norepinephrine, GABA, and serotonin, bufotenine, a hallucinogenic compound. Some new tissues, contain tetrodotoxin.
  • 50.
  • 51. • Snake venom is produced in venom glands in the upper jaws and is delivered through ducts to the base of enlarged teeth (fangs). • These teeth often contain grooves, which may be open or closed, and through which the venom flows and is delivered upon biting. Viperidae, the fangs are basically hollow. • Actual injection of venom is produced by action of a muscle on the venom gland and is under the control of the snake. • Snakes typically deliver doses of venom that may be in the range of 100 times the lethal dose for their prey.
  • 52. Snake venoms the non-enzymatic polypeptides • Dendrotoxins (from mamba venoms) which are potassium channel blockers • Cardiotoxins (from cobra venoms) which produce red cell hemolysis • Erabutoxins (from sea snake venom)Cobratoxins which block the nicotinic acetylcholine receptor • Crotamine (from rattlesnake venom) which acts on sodium channels. Antivenom • Monovalent (specific for one species) or polyvalent (active against several species, typically from the same region). Patient may suffer a hypersensitivity reaction
  • 53. Gila monster Mexican beaded lizard cobra mambas Rattle Snake

Editor's Notes

  1. Whereas a proteolytic strain of C. botulinum (Group I) may cause the food to appear and smell “spoiled” (by-products include isobutyric acid, isovaleric acid, and phenylpropionic acid), this is not the case with nonproteolytic strains, many of which can flourish and elaborate toxin at temperatures as low as 3◦C When spore contaminates the food Botul means sausage
  2. Explain each Emetic- produce their effect by binding to specific receptors in the duodenum, cause vomiting Enterotoxins- action on enteric cells,tell about enteric cells cytotoxic enterotoxins which disrupt the cell membrane or other vital functions of the cell,mostly pore forming,causes the cell to die and cytotonic enterotoxins, which enter the epithelial cell and cause diarrhea without direct membrane disruption or cell death, try and look for examples
  3. Read about layers Shigella spp., Staphylococcus aureus, orEscherichia coli (which releases the shiga-like vero toxin), can elaborate both endotoxin and exotoxin
  4. Read about vagus nerve
  5. Tell about symptoms Droping eyelids Double vision Inability to make facial expression Difficulty in swallowing
  6. Due to various virulence factors There is a relatively wide degree of molecular diversity among SE toxins and this is thought to be the result of adaptation to allow for a broad range of potential hosts Photo in cow mastic
  7. Superantigens (SAgs) are proteins produced by bacteria and viruses that are able to stimulate a large proportion of T lymphocytes via interaction with the variable domain of the β chain of the T cell antigen receptor (TCR-Vβ). Only on ingestion of large amounts of SE
  8. Tell about tampons in menturating women Men and non menstruating women, genitals
  9. Cleavage of synaptobrevin affects the stability of the SNARE core  interfering with exocytosis of neurotransmitters from inhibitory interneurons like gaba and glycine violent spasmatic paralysis ADP- ribosylation of G-protein that controls adenylate cyclase, increase camp conc. Secretion of ions into intestinal lumen, rapid fluid loss and dehydration