The Mess That Is Micro - III - Toxins

Question 0

Bugs with exotoxins that inhibit protein synthesis

Answer 0

How to remember: Dip pseudofed in Shampagne and you will bleed. (note: I doubt you actually will)

Diptheria - diptheria toxin
Pseudomonas - exotoxin A
Shigella - shiga toxin
EHEC - shiga-like toxin

Question 1

Exotoxin A

Answer 1

Pseudomonas aeruginosa (associated with elongation factor 2)

Question 2

Shiga-like toxin

Answer 2

EHEC

Inactivates 60S ribosome (the host’s ribosome!!) by cleaving adenine in RNA. N-glycosidase function - cleaves adenine nucleobase from 28S ribosome.

SLT-toxin enhances cytokine release causing HUS - unlike shigella, EHEC does not invade host cells.

Question 3

Shigella spp. What kind of toxin?

Answer 3

Shiga toxin - inactivates the 60s ribosome in eukaryotic cells by removing adenine from rRNA - n-glycosidase function, cleaves adenine nucleobase from 28S. GI mucosal damage - dysentery, ST also enhances cytokine release causing HUS.

However NOTE THAT the shiga toxin is less important than intestinal invasion in disease pathogenesis because even nontoxin producing shigella produces significant disease!

Question 4

What bacteria release toxins that increase fluid secretion?

Answer 4

Attacking ants vibrate (and secrete fluid to drown their enemies)

ETEC - heat labile and heat stabile toxin
Bacillus anthracis - Edema factor
Vibrio cholera - cholera toxin

Question 5

ETEC - what kind of toxin?

Answer 5

Heat-labile toxin - overactivates adenylate cyclase (increase cAMP) through gs–> increase Cl secretion in gut and H2O efflux.

Heat-stabile toxin - overactivates guanylate cyclase (increased cGMP) leads to decreased resorption of nacl and h2o in the gut.

Remember: labile in the air (adenylate cyclase), stabile on the ground (guanylate cyclase).
Remember: Camp with chlorine if you don’t want to get traveller’s diarrhea and cholera!

Question 6

What bacteria release toxins that increase fluid secretion?

Answer 6

Remember: Attacking (ETEC) ants (Bacillus anthracis) vibrate (Vibrio cholera) (and secrete fluid to drown their enemies)

ETEC - heat labile and heat stabile toxin
Bacillus anthracis - Edema factor
Vibrio cholera - cholera toxin

Question 7

What causes HUS?

Answer 7

Shigella
EHEC

Damage to endothelial cells is the primary event in the pathogenesis of hemolytic-uremic syndrome (HUS). The cardinal lesion is composed of arteriolar and capillary microthrombi (thrombotic microangiopathy [TMA]) and red blood cell (RBC) fragmentation.

Question 8

Verotoxin

Answer 8

Same as shiga-like toxin, produced by EHEC

Question 9

Bacillus anthracis - toxin?

Answer 9

Edema factor - mimics the adenylate cyclase enzyme - increases cAMP

Likely responsible for the characteristic black borders of an eschar in cutaneous anthrax.

Remember: anthrax gives you a black eschar with EDEMA.

Question 10

Bugs that inhibit phagocytic activity?

Answer 10

Bordetella pertussis - pertussis toxin

Question 11

Vibrio cholerae

Answer 11

Cholera toxin / Choleragen - overactivates adenylate cyclase/ cAMP by permanently activating Gs and thus increases Cl secretion in gut and H2O efflux. Leads to voluminous rice water diarrhea.

Remember: Put Chlorine in your water at CAMP or you might get heat labile ETEC and Cholera!

Question 12

Bordetella pertussis toxin?

Answer 12

Pertussis toxin - overactivates adenylate cyclase and increases cAMP by disabling Gi, impairing phagocytosis to permit survival of the microbe. Leads to whooping cough.

Question 13

Pathway for th1, interferon, macrophages, and il-12

Answer 13

This interfering macro is making me Ill

Th1 makes interferon to stimulate macrophages
Mcrophages make il-12 to stimulate th1.

Question 14

Clostridium tetani toxin?

Answer 14

Tetanospasmin - protease that cleaves SNARES proteins required for neurotransmitter release.
Spasticity, risus sardonus, lockjaw, toxin prevents release of inhibitory GABA and glycine neurotransmitters from Renshaw cells in the spinal cord.

Question 15

Clostridium botulinum

Answer 15

Botulinum toxin - protease that cleaves SNARES proteins required for neurotransmitter release.
Flaccid paralysis, floppy baby, toxin prevents release of stimulatory Ach signals at neuromuscular junctions leading to flaccid paralysis.

Question 16

Clostridium perfringens toxin

Answer 16

Alpha toxin- phospholipase - lecithinase- degrades tissue and cell membranes.

Degradation of phospholipids, myonecrosis (gas gangrene) and hemolysis (double sone of hemolysis on blood agar)

Remember: Elves (alpha) on the Fringe (perfringens) are Less (lecithinase) likely to get Gassed (gas gangrene)

Question 17

Strep pyogenes toxins

Answer 17

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 poststreptococcal glomerulonephritis.

Exotoxin A - Brings MHC-II and TCR in proximity to outside of antigen binding site to cause overwhelming release of IFN gamma and IL-2 leading to shock.
Leads to toxic shock syndrome causing fever, rash, and shock

Question 18

Staph aureus toxin

Answer 18

Toxic shock syndrome toxin - TSST-1 - brings MHC-II and TCR in proximity to outside of antigen binding site to cause overwhelming release of IFN gamma and IL-2 leading to shock.

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

Question 19

Endotoxin

Answer 19

An LPS found in outer membrane of gram negative bacteria (both cocci and rods)

Activates macrophages - IL-1, TNF, NO
Activates complement - C3a (hypotension, edema), C5a (neutrophil chemotaxis)
Activates tissue factor - coagulation cascade - DIC

Question 20

Protein A

Answer 20

Binds the Fc region of IgG. Prevents opsonization and phagocytosis, expressed by staph aureus. Basically staph aureus binds the backside of the IgG molecule and uses it as a disguise!

Remember: the A is for staph Aureus.

Question 21

IgA protease

Answer 21

Expressed by the SHIN organisms - strep pneumo, h flu, and neisseria. Enzyme that cleaves IgA. Secreted by these organisms in order to colonize the respiratory mucosa.

Question 22

Lipid A

Answer 22

A component of LPS. Activates macrophages - this leads to widespread IL-1 and TNF alpha release which leads to signs and sx of shock.

Question 23

M protein

Answer 23

Strongly anti-phagocytic and a major virulence factor. Binds serum factor H, destroying C3 convertase and preventing opsonization by C3B. Helps prevent phagocytosis. Expressed by group A strep. Defines strains of strep pyogenes that produce glomerulonephritis.

Remember: when cells are about to be eaten they cry for their MA! (M for M protein, A for group A strep).

Question 24

Lipoteichoic acid

Answer 24

On the surface of gram positives. Induces TNF and IL-1.

Question 25

C difficile’s toxins?

Answer 25

Toxin A - enterotoxin - binds to the brush border of the gut.

Toxin B - cytotoxin - causes cytoskeletal disruption via actin depolymerization - pseudomembranous colitis - diarrhea.

Remember: first you enter (A), then you disrupt the cytoskeleton (B).

Question 26

Toxin A

Answer 26

C difficile

Not to be confused with exotoxin A, which is produced by pseudomonas (Eeeexotoxin, eeelongation factor).

Question 27

Virulence, definition?

Answer 27

Refers to degree of disease that a pathogen can cause. Often quantified in animal models by the LD50.

Important point: beta lactam resistance does not increase the virulence of the organism. Ht does make the infection more difficult to treat!

Question 28

Cereulide

Answer 28

Preformed toxin associated with B. cereus. Nausea and vomiting within 1-5 hours.

Question 29

Pili

Answer 29

N. Meningitidis
N. Gonorrhea
E coli
V cholerae
Pseudomonas

Allows bacteria to adhere to target tissue, establishing infection
Remember: Pills Superficially Calm Callous Men with Guns

It looks like E coli have type I pili and the rest have type IV pili?

Pili for N gonorrhoae are hair-like protein polymers that project from the surface of the cell and are involved in attachment of the organism to mucosal surfaces. They adhere to susceptible cells and thereby begin the infectious process.

Question 30

Cord factor

Answer 30

In virulent strains of mycobacterium, inhibits macrophage maturation and induces release of TNF-alpha.

Question 31

Sulfatides

Answer 31

Surface glycolipids that inhibit phagolysosomal fusion.

Question 32

Lipicolinic acid

Answer 32

In the core of spores.

Question 33

Elek test

Answer 33

Tests for diptheria toxin

Question 34

Salmonella and Shigella - which produces hydrogen sulfide?

Answer 34

Salmonella, not Shigella

Question 36

CAMP factor

Answer 36

Enlarges the area of hemolysis formed by staph aureus, produced by strep agalactiae (group B strep)

Question 37

What is the virulence factor for Staph aureus?

Answer 37

Protein A

Question 38

Hemolysin

Answer 38

Secreted by Staphylococci and cause hemolysis as well as destruction of neutrophils, macrophages, and platelets. A secretedfactor, not bound to cell wall.

Question 39

Spore-forming bacteria

Answer 39

• Bacillus anthracis in soil
• Clostridium (perfringes and tetani in the soil)
• B cereus
• Coxiella burnetti

Fringe (perfringes) Technicians (Tetanus) Seriously (B cereus) Botched (botulinum) up by putting Anthrax Spores in the Closet (Clostridium but we have this) and Burning it (Coxiella burnetti).

They are commonly found in soil and are able to survive high temperatures, dessication, and chemical agents. Kill by autoclaving at 121 degrees for 15 minutes.

Question 40

Enterotoxin

Answer 40

Toxin A, C difficile - binds to brush border of the gut

Question 41

Cytotoxin

Answer 41

Toxin B, cytotoxin, in C difficile - depolymerizes actin filaments causing gastrointestinal mucosal cell death.

Question 42

Which produce hydrogen sulfide, salmonella or shigella?

Answer 42

Salmon smell bad. Hydrogen sulfide also smells bad. So salmonella.

Question 43

Jarisch-Herxheimer reaction

Answer 43

Flu-like syndrome after antibiotics are started due to killed bacteria releasing pyrogens, classically associated with penicillin treatment of syphilis.