Basics of Microbiology: Virulence

Question 1

3 Key Virulence Factors examples to know:

Answer 1

Protein A • IgA protease • M protein

Question 2

Protein A

Key virulence factor of _

Part of _

Inhibits _

Binds _

Prevents _ by macrophages

Prevents _

Answer 2

• Key virulence factor of Staph Aureus • Part of peptidoglycan cell wall • Inhibits phagocytosis • Binds Fc portion of IgG antibodies • Prevents opsonization and phagocytosis by macrophages • Prevents complement activation

Question 3

IgA Protease

• Enzymes that cleave _ which is important for_
• Protease allows _

3 examples:

Answer 3

• Enzymes that cleave IgA • IgA key for mucosal immunity • Protease allows colonization of mucosal surfaces •

S. pneumonia • H. influenza • Neisseria (gonorrhoeae and meningitidis)

Question 4

M Protein

Surface molecule of _, causes _&_

prevents _

Binds _

Breaks down _ prevent _ by C3b

Answer 4

Surface molecule of group A strep (pyogenes) • Strep throat, rheumatic fever • M protein prevents phagocytosis • Binds factor H • Breaks down C3-convertase, prevent opsonization by C3b

Question 5

M Protein

Shares properties _

name 2 Post-strep complications

Answer 5

Shares properties with myosin • May be the basis of rheumatic heart disease •

Post-strep complications:

Rheumatic heart disease • Glomerulonephritis •

(Different M protein subtypes associated each complication)

Question 6

Endotoxin vs Endotoxin

Answer 6

Endotoxin

Only in gram (-) bacteria • Component of outer cell membrane • Lipopolysaccharide (LPS)

Exotoxin

Proteins synthesized by some bacteria

Question 7

Endotoxin

All have _

Answer 7

All have lipid A core • Responsible for most of the toxicity •

O antigen • Terminal end sugars that vary among bacterial strains • Do not cause disease by themselves

Question 8

Endotoxin

Can cause _ (2 things)

triggers _ and _release- which are key immune components of sepsis and septic shock

Generates weak _ -Can’t vaccinate against endotoxin •

Heat _

Answer 8

Can cause fever, shock • Triggers TNF and IL-1 release • Key immune components of sepsis and septic shock • Generates weak antibody response • Can’t vaccinate against endotoxin • Heat stable (tolerates high temps)

Question 9

how exactly does LPS cause fever and hypotension?

Answer 9

Question 10

important example of Lipooligosaccharide

Answer 10

Neisseria meningitidis

Endotoxin • Similar to LPS with some structural differences • Lacks O-antigen • Found on non-enteric gram negatives

Question 11

exotoxin Protein Synthesis Inhibitors: (4)

Answer 11

Corynebacterium diphtheria • Pseudomonas aeruginosa • Shigella • Enterohemorrhagic E. Coli (EHEC)

Question 12

2 ADP Ribosylation exotoxins:

Answer 12

Two toxins work by adding ADP-Ribose to proteins

Diphtheria toxin

Exotoxin A (pseudomonas aeruginosa)

Addition of ADP-Ribose makes protein dysfunctional

Question 13

Diphtheria toxin Inactivates

Answer 13

elongation factor (EF-2) which is necessary for protein synthesis

(Sore throat with membrane, swollen nodes)

Question 14

Shigella

Causes ___

Secretes __

Binds to __

Halts __

Special note: ___is main cause of disease as evidenced by___

Answer 14

Causes infectious diarrhea • Secretes shiga toxin • Binds to 60S ribosome in cells • Removes a specific adenine residue from rRNA in the 60S ribosomal subunit • Halts protein synthesis • Special note: • Invasion of GI mucosal cells is main cause of disease as evidenced by Non-toxigenic strains that cause significant disease

Question 15

Enterohemorrhagic E. Coli

produce __

Same mechanism as __

Typically causes ___

Classic serotype is ___

Does not __

Disease from ___

Answer 15

“shiga-like” toxin • Same mechanism as shiga toxin • Typically causes bloody diarrhea • Classic serotype is E. coli O157:H7 • Do not invade host cells • Attach to intestinal epithelial cells • Disease from secretion of proteins into host cells • Toxin

Question 16

exotoxin Increase Fluid Secretion 3 examples:

Answer 16

Enterotoxigenic E. Coli (ETEC) • Bacillus anthracis • Vibrio cholera

Question 17

how does Fluid Secretion in GI Tract work?

Answer 17

Question 18

E. Coli Heat Labile Toxin

Activates____

Increases_____

Answer 18

Activates adenylate cyclase (↑cAMP) and therefore activates CFTR

Increases water in gut → diarrhea

Question 19

E. Coli Heat Stable Toxin

Activates ____

Increases ___

Stimulates_____

Inhibition of sodium chloride absorption • More water in gut → diarrhea

Answer 19

• Activates guanylate cyclase • Increases cGMP • Stimulation of chloride secretion • Inhibition of sodium chloride absorption • More water in gut → diarrhea

Question 20

Bacillus Anthracis makes exotoxin that___

makes three proteins:

edema toxin:

Mimics ___

Skin and GI lesions often have

Answer 20

stimulates fluid secretion

three proteins: protective antigen (PA), lethal factor (LF), and edema factor (EF), alone no harm, In pairs they produce toxicity •

Edema toxin = PA + EF

Mimics adenylate cyclase

Skin and GI lesions often have edematous*** ***borders!!!!!

Question 21

Vibrio Cholera toxin:

Permanently activates___

Voluminous ____ diarrhea

Common in areas with lack of _____

mainstay of treatment____

Answer 21

Cholera toxin • Permanently activates Gs → ↑cAMP

Voluminous “rice-water” diarrhea • Common in areas with lack of clean water

Death: profound dehydration, electrolyte losses, shock

Aggressive volume repletion is mainstay of treatment

Question 22

exotoxin Inhibitors of Phagocytosis: 1 example

Answer 22

Bordetella pertussis (whooping cough)

Question 23

Pertussis toxin

inhibit ___

Allows over-activation of ___

Result: impaired___

Answer 23

inhibit Gi proteins • Allows over-activation of adenylate cyclase • ↑cAMP levels in cells in neutrophils • Result: impaired recruitment of neutrophils

Question 24

Neurotoxins 2 examples:

both work by:

Answer 24

Clostridium tetani • Clostridium botulinum • Both work by disruption of SNARE proteins

Question 25

Clostridium tetani

toxin:

works in

inhibits

result: ___paralysis

Answer 25

Tetanospasmin

Works in spinal cord (Renshaw cells)

Inhibits inhibitory neurons (GABA and glycine)

Result: Muscles always on (rigid)

Question 26

Clostridium botulinum

toxin:

works at:

prevents:

result: __paralysis

Answer 26

Botulinum toxin

Works at neuromuscular junctions

Prevents Ach release (no muscle contraction)

Result: Muscles floppy (flaccid paralysis)

Question 27

Lysis of Cell Membranes exotoxin 2 examples

Answer 27

Clostridium perfringens • Strep pyogenes

Question 28

Clostridium perfringens

_ toxin, which is a:

degrades:

causes:

forms:

results:

Answer 28

Alpha toxin • Phospholipase C enzyme

Degrades phosphatidylcholine and sphingomyelin

Muscle breakdown (myonecrosis) & Causes a decline in muscle blood flow

Forms occlusive plugs: platelets, leukocytes, fibrin

Result: Low O2 environment favorable to bacteria

Question 29

Strep Pyogenes toxin:

Responsible for

diagnosis:

Answer 29

Streptolysin O • “Cytolysin” (lysis cells)

Responsible for beta hemolysis (also streptolysin S)

Anti-streptolysin O (ASO) antibodies

Elevated following strep infection, Can be useful in suspected rheumatic heart disease or poststrep glomerulonephritis

Question 30

Toxoid Vaccines:

Answer 30

DTaP combined immunization • Toxoids: Diphtheria &Tetanus

also has “Acellular” Pertussis (inactive toxin plus bacterial elements)

Question 31

Exotoxin Genetics

Many exotoxin genes not __rather, come from

Answer 31

Plasmid-encoded • E. coli heat-labile toxin

Bacteriophage-encoded • Corynebacterium diphtheriae*** • Strep pyogenes erythrogenic • E. Coli shiga-like toxin • Botulinum toxin • Cholera toxin

Question 32

two bacteria that synthesize Superantigens:

both cause:

Answer 32

Staph aureus • Toxic shock syndrome toxin (TSST-1)

Strep pyogenes (group A strep) • Pyrogenic exotoxin A or C

• Both can cause toxic shock syndrome

Question 33

Toxic Shock Syndrome, might look like sepsis but 2 huge clues are:

Answer 33

might look like sepsis due to Fever, shock (hypotension), but 2 clues its toxic shock are:

Diffuse, red rash

Diarrhea