Bacterial Pathogenesis II

Question 1

Toxins (types)

Answer 1

Virulence factors (excreted or not)

Type I: bind and act at host cell surface - Super antigens

Type II: act on host cell mems - phospholipases and pore-forming toxins

Type III: A-B toxins, includes single chain -DT and BoNT and multisubunit toxins - cholera and antrhax

Question 2

Other ways to categorize toxins

Answer 2

• Non-protein and protein toxins.
• Endotoxin versus exotoxin.
• Effector proteins (cytolysins, injected into host cells via T3SS or
  other secretion systems).

Question 3

Non-protein Toxins

Answer 3

Stims TLR4 or TLR2/6

• Septic shock, DIC, Acute Resp syn
• Sepsis kills many people

Sims Nod1
-arrests ciliary movement, causes extrusion of ciliated cells, IL1 release, coughing, secondary infections

Stims TLR2 and Nod1/2
-killer

*LPS

Question 4

Mycobacterium ulcerans Polyketide-derived Mycolactone

Answer 4

toxin encoded on large plasmid*
-Causes apoptosis/necrosis of
host cells without inflammation or pain (induces analgesia)
- Causes Buruli ulcers
- Necrotic lesions can cover up to
15% of body. - Eventually heal, leaving scars.
Can cause death.

M ulcerans

Question 5

Exotoxins

Answer 5

super antigens, can clamps together antigen presenting cell and T cells

Superantigen forms bridge
between APC and T cells
and results in massive
outpouring of cytokines

T cells become activated
and then exhausted & die

That may be an advantage
to the bacteria

Diarrhea promotes
dissemination

Question 6

Superantigens

Answer 6

bind calss II MHC outside peptide celf, recognized by less variant regions of TCR families, cell dies and depressed immunity

Question 7

Staphylococcus aureus

Answer 7

community acquired very resistant to antibiotics

up to 1/3rd nasal colonized
survives on skin, gowns, gloves, enviro

Question 8

Types of staph aureus

Answer 8

1. Hospital acquired-methicillin-resistant (HA-MRSA)
   - from staff to patient
2. Community acquires (CA) MRSA
   - day care, wrestlers
   - colonization of skin > nose

*Together these responsible for more deaths than HIV (20,000/yr)

Question 9

Staph aureus causes?

Answer 9

food poisoning
bacteremia/sepsis
toxic shock syndrome
abscesses 
cellulitis

Question 10

Staph aureus surface membrane

Answer 10

Loaded with mols that interact with the host

adhesins
capsule
Protein A
MSCRAMMs

Question 11

Staph Toxic Assets

Answer 11

Toxic shock syndrome toxin 1 (TSST-1, superantigen)

Staph Enterotoxins SEA-SEE: food poisoning, phage encoded (emetics and pyrogenic factors)

Exofoliative toxins: scalded skin in kids, separated skin layers

Leukocidins: lyse WBCs

Staphlokinase: mimic tissue plasminogen activator

Alpha-toxins: alpha hemolysin

• Virulence factors regulated by Quorum sensing
• two component

Question 12

Quorum Sensing

Answer 12

for communication and acting in groups, high density changes beh

some can sense hormones produced by host
- Adrenergic sensing in EHEC

Question 13

Agr quorum sensing in staph aureus

Answer 13

*Virulence factors regulated by Quorum sensing

Two component sys

1) AgrC = sensor kinase
2) AgrA = response regulator

witch hazel inhibits MRSA quorum sensing

Question 14

Membrane disrupting toxins

Answer 14

Phospholipases: hydrolyzes the lipid lecithin and contributes to gangrene (alpha toxin of C perferingens)
-Eats plasma mem causes necrosis

Pore-forming toxins: swelling and cell lysis, can integrate into host mem and forms a channel ions and water can rush into and lyse cells like RBS

• hemolytic: lysing red blood cells on red agar plate
• alpha (helices)
• beta (beta-barrel)
• 30% of all known bac toxins
• Can create pores from 250 nm in diameter.

Question 15

Aerolysin

Answer 15

intoxication of host cells via a screw or swirling mem insertion mech

Question 16

Pore-Forming Toxins (PFTs)

Answer 16

Disrupts vacuolar mems
Destructs tissue barriers
Host cell lysis and release nutrients
Inactivation of phagocytes