L8.Virulence Factors

Question 1

What are the main 2 types of adherence & colonization virulence factors? What is different about each?

Answer 1

1. Pili - Form protein (pili) - Sugar (glycolipid/glycoprotein) interactions. Not as strong.
2. Adhesins - Form Protein (Adhesin) - Protein (often Integrin CR3) interactions. Stronger.

Question 2

What common strain of gut bacteria uses Pili?

Answer 2

E. coli strains

Question 3

What are 3 types of pili, used by 3 types of E. coli? How does each pili affect the virulence of each E. coli strain?

Answer 3

1. Common pili: Used by ALL E. coli strains.
   
   • Common pili are NOT associated w/ disease
   • Common pili recognize Manose (sugar)
2. Type I pili: Used by Enterotoxigenic E. coli.
   
   • Type I pili contain Colonization Factor Antigens I & II (CFAs I/II).
   • CFAs are the most important virulence factor for E. coli. W/o CFA I & II E. coli doesn’t cause diarrhea.
3. P pili: Used by Uropathogenic E. coli
   
   • P pili recognize Galactose rich surface antigens, which are in high abundance in the urinary tract.
   • P pili increase virulence so uropathogenic E. coli can cause urinary tract infections

Question 4

Are adhesins more common in gram+ or gram- bacteria?

Answer 4

Gram-

Question 5

What is so special about the 2 adhesins, Filamentous hemagglutinin (Fha) and Pertussis toxin (Ptx), produced by B. pertussis?

Answer 5

B. pertussis adhesins Fha and Ptx are special b/c they form very tight bonds with the host cellular receptor protein Integrin CR3. This extremely strong bond allows the B. pertussis to attach to respiratory tract and cause infection

Question 6

N. gonorrhea uses both Pili and Adhesins to attach to the urinary tract host cell. How does this increase N. gonorrhea’s virulence?

Answer 6

1. The pili seeks out and forms the initial attachment
2. Adhesin PI forms intimate (stronger) association and during phagocytosis, Adhesin PII prevents phagolysosome formation.

Question 7

1. What type of bacteria generally have virulence factors that allow them to invade host cells & tissues?
2. What 2 benefits do they get out of this invasion?

Answer 7

1. Obligate Pathogens, such as Chlomidea, which can only replicate inside a host cell
2. Once inside the host cell there is plenty of nutrients and the cell provides defense against immune system & drugs (hard to treat)

Question 8

What are the 2 mechanisms by which bacteria invade nonphagocytic host cells? Describe each and give an example

Answer 8

1. ‘Zipper’ mechanism - Bacteria forms extremely tight association w/ host cell surface receptor. This causes cell to internalize bacteria to stop association. Adhesin-Integrin association
2. ‘Trigger’ mechanism - Bacteria, such as Salmonella, bind to receptor protein starting a signalling cascade that results in cytoskeleton change that allows bacteria to enter cell

Question 9

M. tuberculosis enters phagocytic cells. How do they avoid being killed? Give 3 mechanisms

Answer 9

• Doesn’t need to expend energy to get inside cell but must be able to survive.
  1. Bacteria interact w/ specific host cell receptor that does not trigger phagolysosome.
  2. Bacteria may inhibit lysosomal binding. N. gonorrhea does this w/ its PI adhesin receptors on surface
  3. Escape into cytoplasm

Question 10

Staph aureus uses what virulence factor against complements to mask its surface components?

Answer 10

S. aureus uses a CAPSULE to avoid detection by masking its surface proteins

Question 11

Once in bloodstream Meningococcus spp will quickly be covered by circulating IgA antibody. How does this provide increased virulence?

Answer 11

The coating of Meningococcus spp in IgA avoids them being coated in IgG antibody, which activates the complement system.

Question 12

What enzyme does Strep. pyogenes produce to avoid detection by the complement system?

Answer 12

S. pyogens produces C5a peptidase, which cleaves the C5a messenger peptide of the complement system

Question 13

Gram- bacteria such as Salmonella produce what too block access of the membrane attack complex of the complement system to their cell surface?

Answer 13

Long lipopolysaccharide chains (=LPS chains).

Question 14

Name 5 anti-phagocytic virulence factors expressed by bacteria. Briefly describe.

Answer 14

1. Capsules - avoid detection
2. Producing enzymes capable of lysing phagocytic cells. Streptolysin by S. pyogenes
3. Protein A - produced by strep, staph & others causes the inverse expression of immunoglobulins on the bacterial surface so that can’t be detected
4. M protein - Produced by S. pyogenes. Recruits serum factor H to lyse C3b, a compliment protein part of the membrane attack complex
5. Escaping into cytoplasm, inhibiting the fusion of phagolysozomes & resisting lysosomal enzymes & oxidative killing. - M. tuberculosis

Question 15

What is Antigen Variation?

Answer 15

Certain bacterial species have the ability to variably express their surface proteins (pilins). Thus, when the immune system targets Pilin A the bacteria will switch to expressing Pilin B.

Question 16

What are superantigens?

Answer 16

They are toxins expressed as antigens that falsely activate all T cells. Leaves no more T cell defense. What leads to toxic shock.

Question 17

What are the 2 types of bacterial toxins? describe each

Answer 17

1. Exotoxin: a toxin secreted into the surrounding env’t
2. Endotoxin: The LPS of outer membrane of Gram- bacteria (attached to bacteria). If released into the env’t act as regular toxin.

Question 18

How does endotoxin LPS work?

Answer 18

1. When bacteria are lysed by immune system Lipid A (toxic portion) is exposed.
2. LPS binds to CD14 binding site on macrophages inducing immune system response.
3. This response is fine if LPS is at low concentration. If high concentration of LPS, however, causes over-activation of immune system and endothelial damage

Question 19

Certain bacterial virulence factors cause host tissue damage resulting from immune response to bacteria. What are the two types outlined in class?

Answer 19

1. Bacterial products trigger immune response: If the presenting bacterial antigen resembles a host cell, such as some M protein antigens on Strep spp that resemble heart proteins, the host immunity system will produce antibodies or cytotoxic T cells that are capable of attacking host cells
2. Bacterial Pathogens Elicit Inflammatory Response: Prolonged, un-contained inflammatory responses can cause serious damage & sometimes death. Seen in TB. The bacteria doesn’t cause any damage, all negative affects of TB come from host inflammatory immune response

Question 20

Can a single protein stemming from a single gene incur virulence to a bacterial cell?

Answer 20

Yes, Invasin is an example that when put into E. coli makes pathogenic

Question 21

What are the 2 types of extrachromosomal determinants of pathogenicity?

Answer 21

1. Plasmid-encoded virulence factors

2. Bacteriophage-encoded virulence factors

Question 22

What are Pathogenicity Islands? What do they say about the transferability of chromosome based virulence genes?

Answer 22

Pathogenicity Islands are small regions of DNA that encode for a number of virulent factors. B/c Pathogenicity islands are probably foreign (b/c G-C content doesn’t match rest of chromosome) and they are bunched together it suggests that even chromosomal virulence factors are easily transferred from 1 bacteria to another.

Question 23

How are pathogenicity Islands believed to be passed from one bacteria to another?

Answer 23

Transduction via Bacteriophages.

Question 24

How do pathogenicity islands explain the close relation of E. coli & Salmonella genomes and the large difference in their virulence?

Answer 24

Salmonella started out like E. coli but picked up 3 pathogenicity islands along the way. 1st gave salmonella ability to invade cell; 2nd gave ability to survive in cell; 3rd gave ability to survive in macrophages.