Week 14.3 Virulence Factors

Question 1

Virulence factors

Answer 1

molecules that facilitate a pathogen’s colonization, survival, and reproduction in or on a host
-determine severity and extent of disease they cause

Question 2

Major types of virulence factors

Answer 2

1. Adhesins
2. Exoenzymes
3. Toxins
4. Immune evasion

Question 3

Adhesins

Answer 3

facilitate colonization of the host or invasion of host cells by binding to specific ligands

Question 4

Exoeznymes

Answer 4

enable pathogens to invade host cells or deeper tissues

Question 5

Four classes of exoenzymes

Answer 5

1. Glycohydrolases
2. Nucleases
3. Phospholipases
4. Proteases

Question 6

Glycohydrolases

Answer 6

exoenzymes that degrade hyaluronic acid that cements cells together to promote spreading through tissues

Question 7

Nucleases

Answer 7

exoenzymes that degrade DNA released by dying cells (bacteria and host cells) that can trap the bacteria, thus promoting spread

Question 8

Phospholipases

Answer 8

exoenzymes that degrade phospholipid bilayer of host cells, causing cellular lysis, and degrade membrane of phagosomes to enable escape into the cytoplasm

Question 9

Proteases

Answer 9

exoenzymes that degrade collagen in connective tissue to promote spread

Question 10

Toxins

Answer 10

1. Endotoxin
2. Exotoxin

Question 11

Endotoxin

Answer 11

-Gram (-)
-general systemic symptoms of inflammation and fever

Question 12

Exotoxin

Answer 12

-Gram (+) primarily but also gram (-)
-specific damage to cells dependent upon receptor-mediated targeting of cells and specific mechanisms of action

Question 13

Example of an endotoxin

Answer 13

Lipopolysaccharide
-During an infection, pathogens release endotoxins when the cell dies or replicates. Lipid A component is a strong stimulator of the immune response
-high concentrations of endotoxin can cause excessive inflammatory response, severe drop in BP, multi-organ failure, or death

Question 14

Categories of exotoxins

Answer 14

1. Intracellular-targeting toxins
2. Membrane-disrupting toxins
3. Superantigens

Question 15

Intracellular-targeting toxins

Answer 15

Exotoxins that target the inside of a cell
1. B subunit binds to specific membrane-bound receptor on target cell
2. Binding stimulates endocytosis
3. A subunit is then hydrolyzed and released into cell
4. Response

Question 16

Membrane-disrupting toxins

Answer 16

exotoxins that form pores in membrane of target cell or degrade components of phospholipid bilayer

Question 17

Superantigens

Answer 17

exotoxins that stimulate excessive activation of the immune response

Question 18

Immune evasion

Answer 18

Capsules and biofilms, proteases

Question 19

Capsules (immune evasion)

Answer 19

provides physical protection from antibodies

Question 20

Biofilms (immune evasion)

Answer 20

prevent macrophages from inducing phagocytosis

Question 21

Proteases (immune evasion)

Answer 21

degrade antibodies

Question 22

How were virulence factors discovered?

Answer 22

Koch’s Postulates
1. The suspected causative agent must be absent from all healthy organisms but present in all diseased organisms
2. The causative agent must be isolated from the diseased organism and grown in pure culture
3. The cultured agent must cause the same disease when inoculated into a healthy organism
4. The same causative agent must be reisolated from the inoculated organism

Question 23

Discovering and describing virulence factors requires evidence of four things

Answer 23

1. Disease Correlation: virulence factor is present in the pathogen when it causes disease
2. Experimental Evidence: Koch’s postulates with toxins or knockout strains; VF contributes to severity
3. Biological Plausibility: mechanism could reasonably cause the damage
4. Epidemiologic Consistency: the expected outcomes are the outcomes we actually observe