Bacterial Exotoxins

Question 1

Exotoxins v. Endotoxins

Answer 1

Exo

• secreted from both gram pos and neg
• polypeptides –> high antibody titer (toxoids can be used as vaccine)
• more potent (need less) but more heat labile
• encoded by plasmid or phage

Endo

• outer cell mem of almost all gram neg; lipid A of LPS
• Induce TNFalpha, IL-1 and IL-6 –> fever, shock, DIC
• No vaccines
• less potent (need more) but more heat stable for 1 hr
• encoded by bacterial chromosomes

Question 2

Diphtheria Toxin

Answer 2

Inactivates EF2

Pharyngitis w/ pseudomembranes in throat and bull neck lymphadenopathy

Question 3

Pseudomonas Exotoxin A

Answer 3

Inactivates EF2 –> host cell death

Question 4

Shiga Toxin

Shiga-Like Toxin

Answer 4

Shigella and EHEC

Inactivate 60s ribosome by removing adenine from rRNA

• In Shigella … GI mucosal damage and inc cytokine release leading to HUS (invades host cell)
• In E coli … inc cytokine release leading to HUS (does not invade host cell) O157:H7

Question 5

ETEC Toxins

Answer 5

Heat Labile - inc adenylate cyclase –> inc cAMP –> inc Cl- secretion in gut and H2O efflux

Heat Stable - inc guanylate cyclase –> inc cGMP –> dec resorption of NaCl and H2O in gut

WATERY DIARRHEA

“Labile in the Air - AMP and stable on the Ground - GMP”

Question 6

Edema Toxin

Answer 6

Bacillus anthracis

Mimics adenylate cyclase - inc cAMP

Edematous borders of black eschar

Question 7

Cholera Toxin

Answer 7

Vibrio cholera

Overactivates adenylyl cylase –> inc cAMP by permanent G alpha s activation –> inc Cl- and H2O efflux in gut

RICE WATER DIARRHEA (voluminous)

Question 8

Pertussis Toxin

Answer 8

B pertussis

Overactivate adenylyl cyclase by inactivating G alpha i - impairs phagocytosis to permit survival of microbe

Whooping cough - toxin may not actually cause cough

Question 9

Tetanospasmin v Botulinum toxin

Answer 9

Tetanus - protease that cleaves SNARE at GABA and glycine vesicles of Renshaw cells (spastic paralysis)

Bot - protease that cleaves SNARE at Ach release in NMJ (flaccid paralysis)

SNARE = set of proteins requires for vesicle fusion for neuroT release

Question 10

Alpha toxin

Answer 10

Clostridium perfringens

Phospholipase that degrades tissue and cell membranes

Degradation of phospholipids –> myonecrosis –> gas gangrene and hemolysis (dble zone of hemolysis on blood agar)

Question 11

Streptolysin O

Answer 11

Strep pyogenes (group A strep)

Protein that degrades cell membrane –> lyses RBCs (contributes to the beta hemolysis of this bacteria)

Host antibodies against this toxin (ASO) used to dx rheumatic fever (UNLIKE PSGN WHICH IS IMMUNE COMPLEX MEDIATED)

Question 12

TSST-1

Answer 12

Toxic Shock Syndrom Toxin

Staph aureus

Binds MHC II and TCR outside antigen binding site –> overwhelming release of IL-1, IL-2, IFN-gamma and TNF-alpha –> SHOCK

Question 13

Exotoxin A

Answer 13

Strep pyogenes

Binds MHC II and TCR outside antigen binding site –> overwhelming release of IL-1, IL-2, IFN-gamma and TNF-alpha –> SHOCK

Causes “toxic shock like syndrome” and scarlet fever

Question 14

Endotoxin

Answer 14

LPS = O antigen + core polysaccharide + lipid A (TOXIN)

Lipid A - released when cell is lysed or by blebbing off membrane of living cell

3 main effects …
1- macrophage act (TLR4)
2- Complement activation (C3a/C5a - histamine / neutrophils)
3- tissue factor activation (coag - DIC)