Bugs With Exotoxins, Plus Endotoxin

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Corynebacterium diphtheriae

toxin is an 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

Back 1

-inhibits protein synthesis

-diphtheria toxin (an A-B toxin)
-inactivates elongation factor (EF-2)

-manifests as phrayngitis with pseudomembranes in throat and severe lymphadenopathy (bull neck)

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Psudomonas aeruginosa

-A-B toxin

Back 2

-inhibits protein synthesis

-exotoxin A (an A-B toxin)
-inactivates elongation factor (EF-2)

-causes host cell death

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Shigella species

Back 3

-inhibits protein synthesis
-Shiga toxin (ST), an A-B toxin
-inactivates 60S ribosome by removing adenine from rRNA

-GI mucosal damage --> dysentery
-ST also enhances cytokine release, causing hemolytic-uremic syndrome (HUS)

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EHEC: entero-hemorrhagic E. coli

-includes O157:H7 strain

Back 4

-inhibits protein synthesis

-shiga-like toxin (SLT), an A-B toxin
-inactivates 60S ribosome by removing adenine from rRNA

-SLT enhances cytokine releases, causing HUG
-but unlike Shigella, EHEC does not invade host cells

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ETEC: enterotoxigenic E. coli

-two toxins

-cause watery diarrhea

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-Increases fluid secretion

-Heat-labile toxin (LT), an A-B toxin
-overactivates adenylate cyclase (inc. cAMP), causing inc. Cl- secretion in gut and H2O efflux

-Heat-stable toxin (ST)
-overactivates guanylate cyclase (inc. cGMP), causing decreased resorption of NaCl and H2O in gut
-"stable on the Ground" (cGMP)

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Bacillus anthracis

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-increases fluid secretion

-toxin is Edema factor
-mimics the adenylate cyclase enzyme (inc. cAMP)
-likely responsible for characteristic edematous borders of black eschar in cutaneous anthrax*

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Vibrio cholerae

Back 7

-increases fluid secretion

-cholera toxin, an A-B toxin
-overactivates adenylate cyclase (inc. cAMP) by permanently activating Gs --> inc. Cl- secretion in gut and H2O efflux

-"CHolera causes CHloride secretion"

-->voluminous rice-water diarrhea

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Bordatella pertussis

Back 8

-pertussis toxin, an A-B toxin
-inhibits phagocytic ability
-overactivates adenylate cyclase (inc cAMP) by disabling Gi, impairing phagocytosis to permit survival of microbe

-Whooping cough:
--child coughs on expiration and "whoops" on inspiration
--toxin may not actually cause cough

--can cause "100-day cough" in adults

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Clostridium tetani

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-inhibits release of neurotransmitter

-toxin = tetanospasmin

-protease that cleaves SNARE proteins required for neurotransmitter release

-spasticity, risus sardonicus, "lockjaw"
-toxin prevents release of INHIBITOR neurotransmitters (GABA, glycine) from Renshaw cells and spinal cord

[Renshaw cells = inhibitory interneurons found in gray matter of spinal cord]

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Clostridium botulinum

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-inhibits release of neurotransmitter

-botulinum toxin

-like tetanospasmin, botulinum toxin is a protease that cleaves SNARE proteins required for neurotransmitter release

-flaccid paralysis, floppy baby syndrome (infant exhibits no muscular tone whatsoever)
-toxin prevents release of STIMULATORY signals (ACh) at neuromuscular junction --> flaccid paralysis

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Clostridium perfringens

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-lyses cell membranes

-alpha toxin
-a phospholipse (lecithinase) that degrades tissue and cell membranes

-degradation of phospholipids --> myonecrosis ("gas gangrene"), and hemolysis ("double zone" hemolysis on blood agar)

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Streptococcus pyogenes

Back 12

-lyses cell membranes

-toxin = streptolysin O
-protein that degrades cell membrane

-lyses RBCs – contributes to beta-hemolysis
-host antibodies against toxin (ASO) used to diagnose rheumatic fever*
--do not confuse with immune complexes of post-streptococcal glomerulonephritis

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Staphylococcus aureus

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-superantigen causes shock

-toxic shock syndrome toxin (TSST-1)
-brings MHCII and TCR in proximity to outside of antigen binding cite --> overwhelming release of IFN-gamma and IL-2 --> shock

-toxic shock shyndrome: fever, rash shock
-other toxins cause scalded skin syndrome (exfoliative toxin) and food poisoning (enterotoxin

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Streptococcus pyogenes

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-superantigen causes shock

-Exotoxin A
-brings MHC II and TCR in proximity to outside of antigen binding site --> overwhelming release of IFN-gamma and IL-2 --> shock

-toxic shock syndrome: fever, rash, shock

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Endotoxin

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-an LPS found in outer membrane of gram-negative bacteria (cocci and rods)

-three major effects of endotoxin (especially lipid A)

-Activates macrophages
--IL-1 --> fever
--TNF --> fever and hypotension
--nitric oxide --> hypotension

-Activates complement
--C3a --> hypotension, edema
--C5a --> neutrophil chemotaxis

-activates tissue factor
--coagulation cascade --> DIC