Toxins Flashcards
Three categories of toxins
Enzymes
Receptor proteins
Inappropriate immune responses
Exotoxins
Are secreted by bacteria and are not integral parts of the bacterial structure
- can act locally or systematically
Ex: diphtheria, cholera, botulinum, shiga, anthrax etc.
Exotoxins
Membrane bound toxins that are on bacteria and are integral parts oft heir membrane
- can act on the host cell structure
- can act as super antigens
- can hydrologic enzymes that splice host enzymes
Ex: LPS and pore forming proteins
Exotoxin subtypes/categories
B subunit: mediates adherence of the toxin to the host cell or aids in allow the toxin to enter the host cell
A subunit: actually produces the toxic affect
can either be synthesized together and then cleaved or separately pending on the bacteria
LPS
Gram negative bacteria endotoxins that is associated with the cell membrane
- possesses a lipid A portion that induces fever and release of IL-1/TNF of macrophages (induce inflammation)
Bacillus anthracis
Gram positive,non motile, facultative anaerobic (but prefers aerobic), spore forming, rod
- is the etiological agent of anthrax*
Produce their virulence factors via plasmid production
Possesses three proteins as the toxins
Bordetella pertussis
Gram negative aerobic coccobacillus
- causative agent of whopping cough*
Possesses two main toxins
- Pertussis toxin (PT)
- hydrolysis cellar NAD+ = inactivates G proteins
- protein vaccinated against*
- Adenylate Cyclase toxin (ACT)
- generates pores in red blood cells = hemolysis
Corynebacterium diphtheria
Gram positive rod
causative agent of diphtheria
Produces 1 major toxin (diphtheria toxin)
- inhibits peptide chain elongation factor (EF-2) = causes inhibition of ribosomes and cell death
- causes new bacterial membrane formation in throat mucosa and leads to suffocation if not fixed*
- high levels of inorganic iron limits growth rate*
Clostridium tetanus
Anaerobic gram positive rod
- causative agent of tetanus*
- contaminates open wounds
Possesses one major toxin (tetanospasmin)
- binds to receptors on presynaptic membranes of motor neurons
- ultimately degrades synaptobrevin which is required for docking of neurotransmitter vesicles on inhibitory presynaptic neurons = spastic paralysis and suffocation
- requires immunization with tetanus toxoid*
Clostridium botulinum
Anaerobic gram-positive spore forming
causative agent of botulinum poisoning
MOST POTENT TOXIN = botulinum toxin
- is heat liable
- absorbed from the gut
- toxin moves to target function similarly to tetanus except it functions differently
Functions to inhibit release of acetylcholine at synapse of presynaptic motor neurons.
- induces flaccid paralysis
Clostridium perfringens
Anaerobic gram positive spore-forming
Are introduced into wounds by contaminated soil of feces
Produces several different toxins but all lead to gas gangrene of the wound
- spores produce gas via replication and digestion of carbohydrates in the host cells
- Also limits blood flow due to the site causing necrosis/hypoxia
Toxins produced by clostridium perfringens
Alpha/beta/epsilon/iota/ enterotoxin
Necrotic B-like
Collagenases and DNAses
Alpha toxin (CPA)
- lecithinase which damages cell membranes by splitting lecithin
- main culprits of gas gangrene in adults *
CPB (gas gangrene in babies) and CPE (food poisoning)
Staph aureus
Gram positive non-motile cocci
Colonies are everywhere and have multiple infections
Produces 5 virulence factors
Virulence factors of staph aureus
Panton- valentine leukocidin (PVL)
- lysis human white blood cells
Alpha- hemolysis (alpha toxin)
- forms pores in all cells
Phenol-soluble modeling (PSMs)
- amphipathic proteins that lyse human cells
ACME and agr proteins
- controls expression of toxins
lysing cells cause release of iron which promotes invasiveness of infection and replication
Staphylococcal enterotoxin
Special type of staph aureus toxin that is absorbed by the gut
-when absorbed, stimulates vagus nerve receptors which induce vomiting
Streptococcus species
Gram positive cocci
Group A are the most dangerous
- (beta) hemolytic and produce pyrogenic exotoxins
- also produce streptococcal pyrogenic exotoxin B which cleaves antibodies
All produce streptolysin S/O which are pore forming
What is the most potent toxin?
Botulinum
Diphtheria is lest potent but still very toxic
Lipid A portion of endotoxins
Parts of the endotoxins that causes fever
- does this by release IL-1 and TNF from macrophages and induces physiologic effects associated w/ inflammation
Bacillus anthracis virulence factors and toxins
Virulence factors = from plasmids
- toxin production
- capsule formation
Contains three toxins
Protective antigen (PA)
- binds to cell and permits entrance
- Lethal factor (LF)
- decreases MAPK which completely inhibits intracellular enzymes = hypoxia and necrosis
- Edema Factor (EF)
- Stimulates massive amounts of cAMP production within host cells = edema
- protective antigen is target for vaccines*
Bordetella pertussis toxins
Pertussis toxin (PT) = hydrolyzes cellular NAD and transfers the released ADP-ribose to deactivate G-proteins
Adenylate Cyclase Toxin (ACT) = Forms pores to lyse RBCs
PT is the toxin used for vaccines
Corynebacterium diptheriae toxin
Encoded in a lysogenic temperate bacteriophage.
Toxin inhibits peptide chain elongation factor (EF-2) by attaching an adenosine diphosphate-ribosyl group
- B subunit allows entrance where as A subunit does the above toxic effect
- toxin production is inversely related to iron availability*
Clostridium tetani toxin
Tetanospasm
- binds to receptors on presynaptic membranes of motor neurons and enters inhibitory cells
- once in the inhibitory cells, degrades synaptobrevin, which is required for inhibitory cells to work
immunizations w/ small amounts of the tetanus toxoid
Clostridium botulinum toxin
most potent toxin, heat labile and absorbed in the gut
- Binds to receptor of presynaptic membranes of motor neurons and initiates proteolysis of target proteins in neurons (SNARE proteins)
- heavy chain binds to the receptor
- light chain actually does the cleaving of the SNARE proteins
- ultimately inhibits release of acetylcholine at the synapses
Clostridium perfringens toxin
Alpha toxin (CPA) - main virulence factor called lecithinase which works to damage cell membranes by splitting lecithin to phosphorylcholine and diglyceride
Beta toxin (CPB) - enterotoxemia primarily in neonatal patients
Enterotoxin (CPE)
- food poising causing agent
Also produces collagenases and DNAases
Panton-valentine leukocidin (PVL)
Is a virulence factos of staph aureus Lysis of human white blood cells
Alpha-hemolysis (alpha-toxin) and hemolysis A
Virulence factor and toxin of staphylococcus aureus respectively
Both Form pores in cells leading to cell lysis by using H1a subunits to generate pores in the membrane
Phenol-soluble modulins (PSMs)
Virulence factor for staphylococcus aureus
Lyse human neutrophils and RBCs by attaching to the cytoplasmic membrane and leading to membrane disintegration
Staphylococcus aureus toxins
All function to damage the cell membranes of host via two ways
- degrade inter-cellar connections
- modulate immune responses
Can induce enterotoxins
- function for food poising and act to stimulate vagus nerve receptors which induces vomiting
Hemolysis B (sphingomyelinase C)
Staphylococcus aureus toxin that affects human keratinocytes, polymorphonuclear leukocytes monocytes and T-lymphocytes
Poke holes in all of these cells
Leukotoxins
Group of Staph aureus toxins that focus on lysing WBCs
Includes but not limited to:
- PVL
- gamma-hemolysin
- Leukotoxin ED
- Leukotoxin AB/GH
Exfoliative toxins
Staph aureus toxins that focus on degrading skin cells by braking adhesions
Includes but not limited to the following:
- epidermolytic toxins
- specific serine proteases
- hydrolyses cadherins
- cleavage of keratinocyte junctions
- induces skin peeling and blister formation
Toxic shock syndrome toxin (TSST-1)
Toxin of select staphylococcus aureus species
Elicits superantigens which bind to MHC class 2 and dont let go. - releases cytokine storms of IL-2, IN-y and TNFs
Pyrogenic exotoxins A and C
Toxins from Group A B-hemolytic streptococci
Act as superantigens toxins that are very similar to TSST-1
SSA and SmeZ act in similar fashions
Streptolysin S and O
GAS pore-forming toxins
S targets RBCs, Leukocytes, platelets and subcellular organelles
O targets macrophages, neutrophils, epithelial/endothelial cells
- impaired phagocytic clearance and is cholesterol- dependent
Streptococcal pyrogenic exotoxins B (SpeB)
GAS toxin
Cysteine/serine protease that cleaves IgG into Fc and Fab fragments (destroyed antibodies other than IgG and compliment)
