Damage by Bacterial Agents

Question 1

List types of damages mediated directly or indirectly by bacteria or bacterial products.

Answer 1

• Cell death
• Pathological alterations of metabolism
• Mechanical effects
• Damage due to inappropriate host responses

Question 2

Reading assignment: Describe the three structural components of lipopolysaccharides (Fig. 1).

Answer 2

1. O-antigen
   - Repeating oligosaccharide subunits
   - Highly variable
   - Antigenic
2. Core polysaccharide
   - Less variable than O-antigen
   - Inner and outer core
3. Lipid A
   - Endotoxin
   - Anchors LPS

Question 3

Reading assignment: Describe the core structure of E. coli R1 and compare it to that of H. influenzae (Fig. 1 and Fig. 2).

Answer 3

• Core structure of E. coli R1 is much longer than that of H. influenzae
• H. influenzae only has on Kdo attached
• E. coli R1 has 3 Kdo units attached (and other stuff)

Question 4

Reading assignment: Describe the chemical structure of E. coli lipid A (Fig. 1 and Fig. 3).

Answer 4

• Widely considered to be close to that optimally recognized by human cellular LPS receptors
• Polysaccharide portion is almost invariably linked to lipid A via a linking Kdo residue at position 6′

Question 5

Describe the effects of the O-polysaccharide on bacterial virulence.

Answer 5

1. Adherence: allow organisms to adhere specifically to certain tissues
2. Resistance to phagocytosis: rough mutants are more readily phagocytosed
3. Protection from complement
4. Hydrophilic carriers for lipid A: resistance to hydrophilic compounds

Question 6

Video: Describe the recognition of LPS by lipopolysaccharide binding protein, CD14, TLR4-MD2 complex.

Question 7

Describe the alarm reactions the body produces in response to endotoxin in low concentrations and explain why these reactions may be protective.

Answer 7

• Activation of macrophages
• Activation of complement
• Production of cytokines and acute phase response
• Inflammation
• Fever (pyrogenic, pyrogen)
• B cell activation and antibody production
• Protective because they help the body recognize pathogens and mount an immune response

Question 8

Define pyrogen (and pyrogenic).

Answer 8

Something that produces fever/productive of fever

Question 9

Define septic shock.

Answer 9

Hypotension due to systemic inflammaory response to infectious agent

Question 10

Describe the four stages of septic shock.

Answer 10

1. Systemic inflammatory response syndrome
   - Temperature higher than 38ºC or lower than 36ºC
   - Elevated heart rate
   - Elevated respiratory rate
   - Abnormally high or low neutrophil/WBC count
2. Sepsis
   - Bacteremia
3. Severe sepsis
   - Organ dysfunction
   - Hypoperfusion
   - Hypotension
4. Septic shock
   - Hypotension despite adequate fluid resuscitation

Question 11

Explain why septic shock is an example of how inappropriate functioning of host defense can
lead to disastrous consequences.

Question 12

Explain why treatment with antibacterial drugs is ineffective after a certain point in the course of septic shock.

Question 13

Describe the main differences between exotoxins and endotoxins.

Question 14

Group exotoxins according to their site of action and give one example for each group.

Question 15

Describe the toxic effect of superantigens.

Question 16

Compare and contrast the toxic effect of phospholipase and α-toxin of Staphylococcus aureus.

Question 17

Describe the general structural properties of an A-B toxin and define the function of the A domain and the function of the B domain.

Question 18

Describe how ADP-ribosylation affects the function of a target protein.

Question 19

Describe the toxic effects of diphtheria toxin and cholera toxin.

Question 20

Compare and contrast the toxic effects of tetanus toxin and botulinum toxin.

Question 21

Explain how elastase facilitates dispersal of invading bacteria.

Question 22

Explain how collagenase facilitates dispersal of invading bacteria.

Question 23

Explain how hyaluronidase facilitates dispersal of invading bacteria.

Question 24

Explain how coagulase facilitates dispersal of invading bacteria.

Question 25

Explain how streptokinase and staphilokinase facilitate dispersal of invading bacteria.

Question 26

Explain how lipase facilitates dispersal of invading bacteria.

Question 27

Explain how IgA protease facilitates dispersal of invading bacteria.

Question 28

What is toxoid and describe the use of toxoid in vaccine development.

Question 29

Explain whether the A portion of an A-B toxin, the B portion, or the whole structure should be used as a vaccine.

Question 30

A protein isolated from the extracellular fluid of a bacterial culture kills cultured mammalian cells. Is this finding sufficient to demonstrate that the protein is a virulence factor of the bacterium from which it was isolated? What would you do to show that this toxin is a virulence factor.