Basics of Microbiology: Virulence Flashcards
3 Key Virulence Factors examples to know:
Protein A • IgA protease • M protein
Protein A
Key virulence factor of _
Part of _
Inhibits _
Binds _
Prevents _ by macrophages
Prevents _
• 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
IgA Protease
- Enzymes that cleave _ which is important for_
- Protease allows _
3 examples:
• Enzymes that cleave IgA • IgA key for mucosal immunity • Protease allows colonization of mucosal surfaces •
S. pneumonia • H. influenza • Neisseria (gonorrhoeae and meningitidis)
M Protein
Surface molecule of _, causes _&_
prevents _
Binds _
Breaks down _ prevent _ by C3b
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
M Protein
Shares properties _
name 2 Post-strep complications
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)
Endotoxin vs Endotoxin
Endotoxin
Only in gram (-) bacteria • Component of outer cell membrane • Lipopolysaccharide (LPS)
Exotoxin
Proteins synthesized by some bacteria
Endotoxin
All have _
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
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 _
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)
how exactly does LPS cause fever and hypotension?
important example of Lipooligosaccharide
Neisseria meningitidis
Endotoxin • Similar to LPS with some structural differences • Lacks O-antigen • Found on non-enteric gram negatives
exotoxin Protein Synthesis Inhibitors: (4)
Corynebacterium diphtheria • Pseudomonas aeruginosa • Shigella • Enterohemorrhagic E. Coli (EHEC)
2 ADP Ribosylation exotoxins:
Two toxins work by adding ADP-Ribose to proteins
Diphtheria toxin
Exotoxin A (pseudomonas aeruginosa)
Addition of ADP-Ribose makes protein dysfunctional
Diphtheria toxin Inactivates
elongation factor (EF-2) which is necessary for protein synthesis
(Sore throat with membrane, swollen nodes)
Shigella
Causes ___
Secretes __
Binds to __
Halts __
Special note: ___is main cause of disease as evidenced by___
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
Enterohemorrhagic E. Coli
produce __
Same mechanism as __
Typically causes ___
Classic serotype is ___
Does not __
Disease from ___
“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
exotoxin Increase Fluid Secretion 3 examples:
Enterotoxigenic E. Coli (ETEC) • Bacillus anthracis • Vibrio cholera
how does Fluid Secretion in GI Tract work?
E. Coli Heat Labile Toxin
Activates____
Increases_____
Activates adenylate cyclase (↑cAMP) and therefore activates CFTR
Increases water in gut → diarrhea
E. Coli Heat Stable Toxin
Activates ____
Increases ___
Stimulates_____
Inhibition of sodium chloride absorption • More water in gut → diarrhea
• Activates guanylate cyclase • Increases cGMP • Stimulation of chloride secretion • Inhibition of sodium chloride absorption • More water in gut → diarrhea
Bacillus Anthracis makes exotoxin that___
makes three proteins:
edema toxin:
Mimics ___
Skin and GI lesions often have
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!!!!!
Vibrio Cholera toxin:
Permanently activates___
Voluminous ____ diarrhea
Common in areas with lack of _____
mainstay of treatment____
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
exotoxin Inhibitors of Phagocytosis: 1 example
Bordetella pertussis (whooping cough)
Pertussis toxin
inhibit ___
Allows over-activation of ___
Result: impaired___
inhibit Gi proteins • Allows over-activation of adenylate cyclase • ↑cAMP levels in cells in neutrophils • Result: impaired recruitment of neutrophils
Neurotoxins 2 examples:
both work by:
Clostridium tetani • Clostridium botulinum • Both work by disruption of SNARE proteins
Clostridium tetani
toxin:
works in
inhibits
result: ___paralysis
Tetanospasmin
Works in spinal cord (Renshaw cells)
Inhibits inhibitory neurons (GABA and glycine)
Result: Muscles always on (rigid)
Clostridium botulinum
toxin:
works at:
prevents:
result: __paralysis
Botulinum toxin
Works at neuromuscular junctions
Prevents Ach release (no muscle contraction)
Result: Muscles floppy (flaccid paralysis)
Lysis of Cell Membranes exotoxin 2 examples
Clostridium perfringens • Strep pyogenes
Clostridium perfringens
_ toxin, which is a:
degrades:
causes:
forms:
results:
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
Strep Pyogenes toxin:
Responsible for
diagnosis:
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
Toxoid Vaccines:
DTaP combined immunization • Toxoids: Diphtheria &Tetanus
also has “Acellular” Pertussis (inactive toxin plus bacterial elements)
Exotoxin Genetics
Many exotoxin genes not __rather, come from
Plasmid-encoded • E. coli heat-labile toxin
Bacteriophage-encoded • Corynebacterium diphtheriae*** • Strep pyogenes erythrogenic • E. Coli shiga-like toxin • Botulinum toxin • Cholera toxin
two bacteria that synthesize Superantigens:
both cause:
Staph aureus • Toxic shock syndrome toxin (TSST-1)
Strep pyogenes (group A strep) • Pyrogenic exotoxin A or C
• Both can cause toxic shock syndrome
Toxic Shock Syndrome, might look like sepsis but 2 huge clues are:
might look like sepsis due to Fever, shock (hypotension), but 2 clues its toxic shock are:
Diffuse, red rash
Diarrhea
