Topic 5 A

Question 1

What is virulence factors

Answer 1

any microbe-produced molecule that helps in the development of disease in the host.
Genes for encoding virulence factors may be located in either mobile genetic elements (MGE) or in pathogenicity
islands (large blocks of chromosomal DNA enriched in virulence factor genes).
This permits individual strains of a given species of bacteria to vary with respect to virulence potential

Question 2

What is endotoxin

Answer 2

consists only of the non-secreted lipopolysaccharide (LPS) carbohydrate only found in the gram-negative bacteria outer membrane. The genes to make LPS are all chromosomally encoded.
The top of LPS is the O-specific polysaccharide which varies within different strains of a bacteria species and defends the bacteria from antibodies and harmful chemicals.
The middle of LPS is the core polysaccharide which is usually identical within the same bacteria species.
The bottom of LPS is the hydrophobic Lipid A which anchors LPS to the lipid bilayer. Lipid A is responsible for the
toxicity of LPS and its recognition activates the human immune system.

Question 3

What is lipid A

Answer 3

Lipid A binds to CD14 which activates macrophage TLR-4 receptors. This triggers the release of IL-1 (fever), tumor necrosis factor (fever, hypotension), and nitric oxide (hypotension).
• Hypotension/Vasodilation increases blood flow to the site of infection, bringing WBCs to the site of infection, and
slowing the blood flow enough for the WBCs to exit the blood vessels.
Lipid A activates complement system: C3a (hypotension, edema) and C5a (neutrophil chemotaxis).
Lipid A activates tissue factor triggers coagulation cascade Disseminated Intravascular Coagulation (DIC).
• This causes widespread formation of blood clots, which can be dangerous in smaller capillaries (kidney/liver).
Higher quantities of Lipid A in the bloodstream triggers Gram-Negative Septic Shock, causing: hypotension, hypovolemia (fluid leak edema), tachycardia, tachypnea (rapid breathing), and leukocytosis (high WBC counts). • Systemic inflammatory response syndrome (SIRS) has the same signs and symptoms as gram-negative septic
shock, but occurs with no evidence of an infection.

Question 4

What is exotoxin

Answer 4

• secreted protein molecules which exist in four major varieties. The genes to make exotoxins are commonly present on plasmids or integrated into the chromosome from phage infection.

Question 5

What are the types of exotoxins

Answer 5

Enterotoxin
Cytotoxin
Neurotoxin
Super-antigen

Question 6

What is enterotoxin

Answer 6

imbalance of water/electrolytes in the intestines, causing diarrhea.

Question 7

What is cytotoxin

Answer 7

kill cells, tissue/organ damage.

Question 8

What is neurotoxin

Answer 8

• interfere with the nervous system, causing paralysis.

Question 9

What is super-antigen

Answer 9

disrupts cytokine signaling, causing inflammation, edema, vascular issues.

Question 10

What are exotoxin secretion systems

Answer 10

Cytoplasm
Extracellular space
Cytoplasm or extracellular space

Question 11

What is cytoplasm type 3,6,7

Answer 11

• exotoxin is delivered from the cytoplasm of bacteria cell directly to the cytoplasm of eukaryotic cell through a syringe-like tub

Question 12

What is extracellular space type 1,2,5

Answer 12

exotoxin is directly secreted into the extracellular space.

Question 13

What is cytoplasm or extracellular space type 4

Answer 13

can use either exotoxin secretion method.

Question 14

What is Exotoxin structure , it’s also part of exotoxin secretion system

Answer 14

exotoxins commonly employ an A-B structure, in which it is comprised of two different protein subunits. The B-subunit binds to the host cell. The A-subunit is the active part which causes harm to the cell.

Question 15

Exotoxin mechanism, what is addictive of a sugar molecule

Answer 15

adds a bulky sugar molecule to a protein, usually causing steric hindrance, preventing it from functioning. ADP-Ribosylation is most common sugar addition.
V. cholerae uses cholera toxin and E. coli uses labile toxin to activate adenylate cyclase, causing diarrhea.

Question 16

Exotoxin mechanisms of action, what is protease

Answer 16

• cleaves a protein.
  C. botulinum uses botulinum toxin and C. tetani uses tetanospasmin to block ACh release, causing paralysis. S. aureus uses exfoliatin toxin to cleave desmoglein within desmosomes, causing scalded skin syndrome

Question 17

Exotoxin mechanisms of action, what is lecithinase

Answer 17

degrades lecithin, an amphiphilic lipid found in eukaryotic cell membranes, killing the cell. C. perfringens uses alpha toxin to kill WBCs.

Question 18

Exotoxin mechanisms of action, what is super-antigen

Answer 18

• triggers deregulation of cytokine signaling pathways.
  S. aureus uses toxic shock syndrome toxin (TSST-1) which binds to TCR and MHC II, triggering IL-1 and IL-2
  release, resulting in toxic shock syndrome. S. pyogenes does the same with erythrogenic toxin.
  S. aureus uses staphylococcal enterotoxin which binds to TCR and MHC II, triggering IFN-γ and IL-2 release,
  resulting in watery diarrhea and vomiting.

Question 19

What is invasion of subcutaneous tissue

Answer 19

proteins/enzymes which aid in the invasion of subcutaneous tissue

Question 20

What is enzymatically controlled invasion of subcutaneous

Answer 20

enzymes which destroy host defenses:
Collagenase degrades collagen and hyaluronidase degrades hyaluronic acid (S. pyogenes & S. aureus cellulitis). Coagulase accelerates fibrin clot formation, cloaking bacteria from the immune system (S. aureus, Y. pestis).
IgA protease destroys IgA antibodies, allowing invasion of tissues. (H. influenzae, S. pneumoniae, N. gonorrhoeae). Leukocidins kills neutrophils and macrophages, letting the bacteria escape initial contact with the immune system

Question 21

What is anti-phagocytic virulence factors

Answer 21

• proteins which prevent phagocytosis:

Question 22

What is capsule

Answer 22

serves as barrier to opsonization (phagocytosis). However, antibodies to the capsule permit
opsonization which is why some vaccinations only contain capsule proteins.

Question 23

What is complement inhibitor protein

Answer 23

• bacteria proteins which prevent activation of the complement system. M Protein in S. pyogenes or Protein A in S. aureus.

Question 24

What is intracellular invasion

Answer 24

hides bacteria from extracellular components of host immune surveillance and response.

Question 25

What is invasins

Answer 25

bacterial surface proteins that bind host cell integrin-family receptors.

Question 26

What is phagocytosis survival

Answer 26

bacteria can enter host cells by surviving phagocytosis via 3 mechanisms:
• Prevent fusion of the phagosome with a lysosome (phagolysosome) to avoid degradative enzymes in the lysosome.
• Prevent acidification of the phagosome by inactivating degradative enzymes in the phagosome.
• Escape the phagosome into the cytoplasm, since there are no degradative enzymes present in the cytoplasm.

Question 27

What is cell to cell invasion

Answer 27

intracellular bacteria can move from one host cell to another by stealing host actin to create a propulsion “rocket” which punches through the current host cell’s membrane and the new host cell’s membrane.

Question 28

What shigella uses

Answer 28

uses a combination of all of these methods. They invade tissues by passing through the M cells of the GI tract. They are then engulfed by macrophages, but survive the phagocytosis attempt and replicate, eventually causing apoptosis of the macrophage. Then they attach to the base of epithelial cells, inducing those cells to engulf them. Once inside, they can use the actin “rocket” method to travel between adjacent epithelial cells

Question 29

What is inflammation

Answer 29

invasion is generally followed by inflammation.

Question 30

What is pyogenic inflammation

Answer 30

• produces pus, primarily composed of neutrophils.

Question 31

What is granulomatou inflammation

Answer 31

• produces a fibrous capsule, primary composed of T-cells and macrophages. This happens when macrophages are unable to destroy bacteria which they engulfed so they form a “jail cell” of scar tissue, trapping the bacteria within. Occurs with mycobacterium tuberculosis which causes tuberculosis (TB).

Question 32

What is adherence to host tissues

Answer 32

instead of invading the tissue, some bacteria just attach to them. This can lead to biofilms!

Question 33

What is adhesins

Answer 33

proteins which allow bacteria to adhere to tissues:
Glycocalyx is a glycoprotein/carbohydrate which is part of the capsule.
Pili are multi-protein complexes used for attachment (also used in lateral gene transfer, movement, or conjugation).

Question 34

What are biofilms

Answer 34

mixture of microorganisms and organic molecules in a tower-like structure. The towers are built out of a matrix of extracellular polymeric substance (EPS), a combination of carbohydrates, proteins, and DNA.

Question 35

What is seeding

Answer 35

when the towers become too full of bacteria, some of them leave and attach to other surfaces, starting formation of a new biofilm.

Question 36

What is quorum sensing

Answer 36

the bacteria inside biofilms release a signaling molecule. When the concentration of this signaling molecule reaches a certain point, it induces expression of genes which result in seeding.

Question 37

What is immunipathogenesis

Answer 37

diseases that result from the immune response to an infection after the infection is cleared. May rarely occur in response to vaccinations

Question 38

What is acute rheumatic fever

Answer 38

occurs 3 weeks after streptococcal pharyngitis (sore throat) by S. pyogenes.
The myosin in muscles are structurally similar to the M Protein used by S. pyogenes so it is targeted by antibodies.
If this occurs in skeletal muscle, it causes chorea movements. In heart muscle, it causes carditis (inflammation of the
heart) and may lead to valve prolapse and the potential that future infections may cause bacterial endocarditis.

Question 39

What is acute post streptococcal glomerulonephritis

Answer 39

occurs 1-3 weeks after wound infection by S. pyogenes.
1) After an infection, leftover bacterial fragments are targeted by antibodies and then engulfed by macrophages.
2) If the infection was massive, there are so many leftovers that the antibody-fragment binding produces a large ball, called an “immune complex”, which gets stuck in the nephrons of the kidney.
3) When this happens, the immune system mistakes the “immune complex” for a large microbe, activating the complement cascade and damaging the nephron.
4) Causes fever, fluid retention, high blood pressure, and blood & protein in the urine (“Coca-Cola” urine).