Bugs with exotoxins Flashcards
Name 4 toxins that inhibit protein synthesis?
- Diphteria toxin from Corynebacterium diphtheriae
- Exotoxin A from Pseudomonas aeruginosa
- Shiga toxin from Shigella
- Shiga like toxin from Enterohemorrhagic E. coli (EHEC) including O157:H7
Among the 4 toxins that inhibit protein synthesis what 2 toxins inactivate elongation factor?
- Diphtheria toxin
2. Exotoxin A
Among the 4 toxins that inhibit protein synthesis what 2 toxins inactivates 60S ribosome by removing adenine from rRNA?
- Shiga toxin
2. Shiga-like toxin
What is the clinical consequence of Diphtheria toxins from Corynebacterium diphtheriae?
Pharyngitis with pseudomembranes in throat and severe lymphadenopathy (bull neck)
What is the clinical consequence of Exotoxin A from Pseudomonas aeruginosa?
Host cell death
What is the clinical manifestation of shiga toxin from shigella?
- GI mucosal damage –> dysentery
2. Shiga toxin also enhances cytokine release –> hemolytic uremic syndrome (HUS)
What is the clinical manifestation of shiga like toxin from EHEC (O157:H7)?
SLT enhances cytokine release –> HUS, but no invasion of host cells, no GI mucosal damage –> thus no dysentery
What are the 4 toxins that increase fluid secretion?
- Heat-labile toxin from Enterotoxigenic E. coli (ETEC)
- Heat-stable toxin from ETEC
- Edema factor from Bacillus anthracis
- Cholera toxin from Vibrio cholerae
What is the mech of heat-labile toxin from Enterotoxigenic E. coli (ETEC)?
Overactivates adenylate cyclase (Inc cAMP) –> Inc Cl- secretion in gut and H2O efflux
What is the mech of heat-stable toxin from ETEC?
Overactivates guanylate cyclase (Inc cGMP) –> Dec resorption of NaCl and H2O in gut
What is the clinical manifestation of both heat-labile and heat-stable toxin?
Watery diarrhea
(labile in the Air, Adenylate cyclase)
(stable on the Ground, Guanylate cyclase)
what is the mech of edema factor from Bacillus anthracis
mimics the adenylate cyclase enzyme –> Inc cAMP
what is the clinical manifestation of the edema factor from Bacillus anthracis?
likely responsible for characteristic edematous borders of black eschar in cutaneous anthrax
what is the mech of cholera toxin from vibrio cholerae?
Overactivates adenylate cyclase (Inc cAMP) by permanently activating Gs –> Inc Cl- secretion in gut and H2O efflux
what is the name of a toxin that inhibits phagocytic ability?
Pertussis toxin from Bordetella pertussis
what is the mech of pertussis toxin from Bordetella pertussis?
overactivates adenylate cyclase (Inc cAMP) by disabling Gi, impairing phagocytosis to permit survival of microbe
what is the clinical manifestation of pertussis toxin from Bordetella pertussis?
whooping cough: child coughs on expiration and “whoops” on inspiration (toxin may not actually be a cause of cough; can cause 100 day cough in adults)
what are the toxins that inhibit release of neurotransmitter?
- Tetanospasmin from Clostridium tetani
2. Botulinum toxin from Clostridium botulinum
what are the toxins that are ADP ribosylating A-B toxin?
- Cholera toxin
- Pertussis toxin
- Heat-labile toxin from Enterotoxigenic E. coli (ETEC)
And all the toxins that inhibit protein synthesis
- Diphtheria toxin
- Exotoxin A
- Shiga toxin
- Shiga-like toxin
what is the mech of ADP ribosylating A-B toxin?
- B (binding) component binds to host cell surface receptor, enabling endocytosis.
- A (active) component attaches ADP-ribosyl to disrupt host cell proteins.
what is the mech of tetanospasmin and botulinum toxin?
both are proteases that cleaves SNARE proteins required for neurotransmitter release
- tetanospasmin –> prevents the release of inhibitory (GABA and glycine) neurotransmitter from Renshaw cells in spinal cord
- botulinum toxin –> prevents release of stimulatory (ACh) signals at neuromuscular junctions –> flaccid paralysis
what is the clinical manifestation of tetanospasmin from Clostridium tetani?
Spasticity, risus sardonicus, and lockjaw
similar to UMN lesions = spastic paralysis
what is the clinical manifestation of botulinum toxin from Clostridium botulinum?
Flaccid paralysis (similar to LMN lesion), floppy baby (Spinal muscular atrophy (Werdnig- Hoffmann disease))
what are the 2 toxins that lyse cell membrane?
- alpha toxin from Clostridium perfringens
2. streptolysin O from streptococcus pyogens
what is the mech of alpha toxin from Clostridium perfringens?
phospholipase (lecithinase) that degrades tissue and cell membranes
what is the mech of streptolysin O?
protein that degrades cell membrane
what are the clinical manifestations of alpha toxin from Clostridium perfringens?
Degradation of phospholipids –> myonecrosis (“gas gangrene”) and hemolysis (“double zone” of hemolysis on blood agar)
what are the clinical manifestations of streptolysin O from Streptococcus pyogens?
- Lyses RBC
2. contributes to beta hemolysis
Host antibodies against toxin ASO is used to diagnose which dz?
Rheumatic fever
what are the 2 superantigens that cause shock?
- Toxic shock syndrome toxin (TSST-1) from Staphylococcus aureus
- Exotoxin A from Strep. pyogens
what is the mech of the 2 toxins, toxic shock syndrome toxin (TSST-1) and Exotoxin A?
Bring MHC II and TCR in proximity to outside of antigen binding site to cause overwhelming release of IFN-gamma and IL-2 –> shock
what are the clinical manifestations of toxic shock syndrome?
fever, rash, shock
what toxin causes scalded skin syndrome?
exfoliative toxin
what toxin cause food poisoning?
enterotoxin
what is endotoxin?
an LPS found in outer membrane of gram negative bacteria (both cocci and rods)
ENDOTOXIN:
Edema Nitric oxide DIC/Death Outer membrane TNF-alpha O-antigen eXtremely heat stable IL-1 Neutrophil chemotaxis
what particular component in endotoxin triggers the immune system?
lipid A
what are the 3 immune systems that endotoxin (lipid A) activates?
- macrophage
- complement
- tissue factor –> coagulation cascade –> DIC
once endotoxin lipid A activates macrophage, what components are then further activated?
- IL-1 –> fever
- TNF –> fever, hypotension
- Nitric oxide –> hypotension