Lecture 4

Question 1

Define “virulence factors”

Answer 1

pathogen-produced products that aid in the establishment and maintenance of infectious disease

Question 2

What are some types of virulence factors?

Answer 2

siderphores, adhesins, toxins, proteolytic enzymes, LPS, capsules, peptidoglycan, and factors that will help them spread

Question 3

What are adhesins?

Answer 3

mediate binding of microbe to some kind of surface

Question 4

What are invasins?

Answer 4

type of adhesin that mediates binding and entry into host cell

Question 5

What are microbial toxins?

Answer 5

product of microbial pathogen that can damage host

Question 6

What are the 2 types of toxins and what are they based on?

Answer 6

based on location inside the cell = can be an endotoxin or exotoxin

Question 7

What is an exotoxin?

Answer 7

made in cytoplasm –> released outside of bacterial cell

Question 8

What is an endotoxin?

Answer 8

made in cytoplasm –> STAYS INSIDE of bacterial cell

Question 9

What is a characteristic of endotoxins?

Answer 9

cell-bound; released in LARGE amounts ONLY when lysed; weak toxicity without being lysed

Question 10

What is the most studied endotoxin?

Answer 10

lipopolysaccharide from gram–

Question 11

What mode of action do endotoxins have and what does it mean? General or specific?

Answer 11

general = all of them work the same way and do the same thing

Question 12

Are endotoxins ever released if not lysed? If so, how?

Answer 12

No, cannot be released without lysis

Question 13

What part/domain is responsible for the endotoxin activity?

Answer 13

Lipid A (base of LPS)

Question 14

What are symptoms caused by LPS?

Answer 14

low conc = fever and stimulates host cell’s immune system; high conc = toxic shock and death

Question 15

What dictates the symptoms of LPS?

Answer 15

the concentration of LPS

Question 16

What are characteristics of exotoxins?

Answer 16

found in all types of bacteria, actively secreted by bacteria

Question 17

What mode of action do exotoxins have and what does it mean? General or specific?

Answer 17

specific and active mechanism

Question 18

At least at what concentration are exotoxins highly toxic?

Answer 18

low concentrations

Question 19

What are 4 ways exotoxins can be named?

Answer 19

based on target (ie:neurotoxin); species that made it (ie: tetanus toxin); activity (ie: proteolytic toxin); by letter (ie: exotoxin A)

Question 20

What are the 3 different types of exotoxins?

Answer 20

super-antigen toxins (I); cytolytic toxins (II); A-B toxins (III)

Question 21

What are super-antigen toxins?

Answer 21

they stay outside the host cell bound onto its surface; does not invade/enter cell

Question 22

What mode of pathogenesis do super-antigen toxins take?

Answer 22

drive the host immune system to attack these host cells (host attacking itself)

Question 23

What are cytolytic toxins?

Answer 23

enters and damages host-cell cytoplasmic membrane = makes an opening/pore –> allows release of cytosol = cell lysis

Question 24

What is an example of a cytolytic toxin?

Answer 24

hemolysins

Question 25

What mechanism of infection do cytolytic toxins do?

Answer 25

synthesized as a polymer then enters host cell and creates a polymer = forming a pore/opening = increaing permeability

Question 26

What are A-B toxins?

Answer 26

either whole or part of toxin will enter host cell

Question 27

What mechanism of infection do A-B toxins do?

Answer 27

A-domain enters host cell and B-domain stays on cell surface receptor; A-domain = exotoxin activity

Question 28

How many subunits can each domain have in A-B toxins?

Answer 28

from one to multi

Question 29

What are 4 cell damage/death mechanisms do toxins cause?

Answer 29

host cell lysis, induction of premature apoptosis, immunoresponse (ie: super-anitgen toxins), and change in metabolism

Question 30

What are 2 ways can bacteria lyse host cells?

Answer 30

destruction of cell membrane or over-multiplication of pathogen inside host cell

Question 31

How will lysing the host cell benefit bacteria? Is this lysis activity active or passive?

Answer 31

provides nutrients and space to grow for bacteria; passive activity, does not mean to kill cells

Question 32

On a blood agar plate, what would signify hemolysin activity?

Answer 32

a clearing around a bacterial colony

Question 33

Why would bacterial pathogens target RBCs?

Answer 33

they don't necessarily target RBCs (passive activity); but it provides as a source of iron

Question 34

What is beneficial about using a blood agar plate assay?

Answer 34

to determine if bacteria produces a type II exotoxin (cytolytic exotoxin)

Question 35

What bacterial species produces diptheria toxin?

Answer 35

Corynebacterium diptheriae

Question 36

What type of toxin is diptheria toxin? How does it affect the host cell?

Answer 36

A-B toxin; premature stop in protein synthesis

Question 37

What is the mode of infection of diptheria toxins?

Answer 37

protease cleaves A-B domains and allows A-domain to enter cell --> A-domain targets and modifies EF2 of ribosome = inhibits tRNA binding to ribosome

Question 38

What is the mode of infection of botulinum toxin?

Answer 38

blocks and prevents release of Ach = reduces and inhibits muscle fiber contractions --> paralysis and death

Question 39

What species produces botulinum toxin and what kind of exotoxin is it?

Answer 39

clostridium botulinum; neurotoxin

Question 40

Where is diptheria toxin found?

Answer 40

viruses genome --- bacteriophage which infects corynebacteria diptheriae

Question 41

How do we measure the lethality of a toxin?

Answer 41

based on its lethal dose by ng/kg (based on weight)

Question 42

What does LD50 stand for?

Answer 42

the lethal dose that killed 50% of people in a study

Question 43

What is the FIRST MOST lethal toxin in the world? What is the second?

Answer 43

Botulinum toxin, tetanus toxin

Question 44

What is the LD50 of botulinum toxin?

Answer 44

2ng/kg

Question 45

What kind of toxin is tetanus toxin and which species produce it?

Answer 45

neurotoxin, clostridium tetani

Question 46

What is the LD50 of tetanus toxin?

Answer 46

3ng/kg

Question 47

What is the mode of infection of tetanus toxin?

Answer 47

prevents release of glycine from neurons = can't stop Ach release = can't relax muscle = constant muscle contractions = paralysis/death

Question 48

What type of toxin is cholera enterotoxin and which species produces it?

Answer 48

A-B toxin by vibrio cholerae (gram–)

Question 49

How many subunits do the A and B domains of cholera enterotoxin have? What is significant about the A-domain?

Answer 49

1 A and 5 B; A-domain has adenyl cyclase activity

Question 50

Which part of the GI tract do enterotoxins act on?

Answer 50

intestines

Question 51

What is the main symptom caused by cholera enterotoxin?

Answer 51

watery diarrhea

Question 52

What is the mode of infection of cholera enterotoxin?

Answer 52

A-domain converts ATP to AMP = causes movement of ions from blood into lumen = changes concentration gradient = makes water move with ions into lumen = watery diarrhea

Question 53

What are 3 applications of toxins?

Answer 53

vaccine development (toxoid), medical uses (ie: botox); biological weapons

Question 54

The B portion of A-B toxins is being used as vaccine components without chemical treatment. Why is it safe to use the B portion as they are?

Answer 54

B-portion has no toxic activity

Question 55

Why is vaccination usually best way to prevent disease caused by A-B toxins?

Answer 55

You can use the A-B toxin as an antigen that your immune system will recognize and target this toxin

Question 56

Why is it better to create a vaccine to target toxins/virulence factors than against the bacteria itself

Answer 56

you may kill/lyse bacteria = release endotoxins; targeting virulence factors decreases the symptoms of the disease

Question 57

How does diptheria toxin contribute to bacterial pathogenesis?

Answer 57

inhibits/prematurely stops protein syntheses