Fa: Microbiology - Basic Bacteriology - 3

Front 1

What is the source of Exotoxins vs. Endotoxins?

Back 1

- Exotoxin: certain species of G+ and G- bacteria
- Endotoxin: outer cell membrane of most G- bacteria

Front 2

Are Exotoxins and/or Endotoxins secreted from cells?

Back 2

- Exotoxin: secreted from cells
- Endotoxin: not secreted

Front 3

What is the structure/chemistry of Exotoxins vs. Endotoxins?

Back 3

- Exotoxin: polypeptide
- Endotoxin: lipopolysaccharide (structural part of bacteria; released when lysed)

Front 4

What is the location of genes of Exotoxins vs. Endotoxins?

Back 4

- Exotoxin: plasmid or bacteriophage
- Endotoxin: bacterial chromosome

Front 5

What is the relative toxicity of Exotoxins vs. Endotoxins?

Back 5

- Exotoxin: high (fatal dose on the order of 1 µg)
- Endotoxin: low (fatal dose on the order of hundreds of µgs)

Front 6

What are the clinical effects of Exotoxins vs. Endotoxins?

Back 6

- Exotoxin: various effects
- Endotoxin: fever, shock (hypotension), DIC

Front 7

What is the mode of action of Exotoxins vs. Endotoxins?

Back 7

- Exotoxin: various modes
- Endotoxin: induces TNF, IL-1, and IL-6

Front 8

What is the antigenicity of Exotoxins vs. Endotoxins?

Back 8

- Exotoxin: induces high-titer antibodies called antitoxins
- Endotoxin: poorly antigenic

Front 9

Are there vaccines for Exotoxins vs. Endotoxins?

Back 9

- Exotoxin: toxoids used as vaccines
- Endotoxin: no toxoids formed and no vaccine available

Front 10

What is the relative heat stability of Exotoxins vs. Endotoxins?

Back 10

- Exotoxin: destroyed rapidly at 60 degrees C (except staphylococcal enterotoxin)
- Endotoxin: stable at 100 degrees C for 1 hr

Front 11

What are the typical diseases associated with Exotoxins vs. Endotoxins?

Back 11

- Exotoxin: tetanus, botulism, diphtheria
- Endotoxin: meningococcemia, sepsis by G- rods

Front 12

Exotoxins
1) Source?
2) Secreted?
3) Chemistry?
4) Location of genes?
5) Toxicity?
6) Clinical effects?
7) Mode of action?
8) Antigenicity?
9) Vaccines?
10) Heat stability?
11) Typical diseases?

Back 12

1) Source: certain species of G+ and G- bacteria
2) Secreted: yes
3) Chemistry: polypeptide
4) Location of genes: plasmid or bacteriophage
5) Toxicity: high (fatal dose on order of 1 µg)
6) Clinical effects: varies
7) Mode of action: varies
8) Antigenicity: induces high-titer antibodies called antitoxins
9) Vaccines: toxoids used as vaccines
10) Heat stability: destroyed rapidly at 60 degrees C (except staphylococcal entertoxin)
11) Typical diseases: tetanus, botulism, diphtheria

Front 13

Endotoxins
1) Source?
2) Secreted?
3) Chemistry?
4) Location of genes?
5) Toxicity?
6) Clinical effects?
7) Mode of action?
8) Antigenicity?
9) Vaccines?
10) Heat stability?
11) Typical diseases?

Back 13

1) Source: outer cell membrane of most G- bacteria
2) Secreted: no
3) Chemistry: lipopolysaccharide (structural part of bacteria; released when lysed)
4) Location of genes: bacterial chromosome
5) Toxicity: low (fatal dose on order of hundreds of µgs)
6) Clinical effects: fever, shock (hypotension), DIC
7) Mode of action: induces TNF, IL-1, IL-6
8) Antigenicity: poorly antigenic
9) Vaccines: no toxoids formed and no vaccine available
10) Heat stability: stable at 100 degrees C for 1 hrs
11) Typical diseases: meningococcemia, sepsis by G- rods

Front 14

What are some possible mechanisms of exotoxins?

Back 14

- Inhibit protein synthesis
- Increase fluid secretion
- Inhibit phagocytic ability
- Inhibit release of NT
- Lyse cell membranes
- Superantigens causing shock

Front 15

What are the characteristics of an ADP ribosylating A-B toxin?

Back 15

- B (binding) component binds to host cell surface receptor
- A (active) component attaches ADP-ribosyl to disrupt host cell proteins

Front 16

Which bacteria release exotoxins that inhibit protein synthesis?

Back 16

- Corynebacterium diphtheriae
- Pseudomonas aeruginosa
- Shigella spp.
- Enterohemorrhagic E. coli (EHEC), including O157:H7 strain

Front 17

Corynebacterium diphtheriae exotoxin:
1) Toxin
2) Mechanism
3) Manifestation

Back 17

1) Toxin: Diphtheria toxin (ADP ribosylating A-B toxin)
2) Mechanism: inactivates elongation factor (EF-2) which inhibits protein synthesis
3) Manifestation: pharyngitis with pseudomembranes in throat and severe lymphadenopathy (bull neck)

Front 18

Pseudomonas aeruginosa exotoxin:
1) Toxin
2) Mechanism
3) Manifestation

Back 18

1) Toxin: Exotoxin A (ADP ribosylating A-B toxin)
2) Mechanism: inactivates elongation factor (EF-2) which inhibits protein synthesis
3) Manifestation: host cell death

Front 19

Shigella spp. exotoxin:
1) Toxin
2) Mechanism
3) Manifestation

Back 19

1) Toxin: Shiga Toxin (ST) - (ADP ribosylating A-B toxin)
2) Mechanism: inactivates 60S ribosome by removing adenine from rRNA, which inhibits protein synthesis
3) Manifestation: GI mucosa damage → dysentery; also enhances cytokine release, causing Hemolytic Uremic Syndrome (HUS)

Front 20

Enterohemorrhagic E. coli (EHEC) exotoxin:
1) Toxin
2) Mechanism
3) Manifestation

Back 20

1) Toxin: Shiga-LIKE toxin (SLT) - (ADP ribosylating A-B toxin)
2) Mechanism:inactivates 60S ribosome by removing adenine from rRNA, which inhibits protein synthesis (same as Shiga Toxin)
3) Manifestation: enhances cytokine release, causing Hemolytic Uremic Syndrome (HUS); but does not invade host cells

Front 21

Which bacteria release exotoxins that increase fluid secretion?

Back 21

- Enterotoxigenic E. coli (ETEC)
- Bacillus anthracis
- Vibrio cholerae

Front 22

Enterotoxigenic E. coli (ETEC) exotoxin:
1) Toxin
2) Mechanism
3) Manifestation

Back 22

1) Toxin: Heat-LABILE toxin (LT) - (ADP ribosylating A-B toxin)
2) Mechanism: overactivates AC → ↑cAMP → ↑Cl- secretion in gut and H2O efflux (same as cholera toxin)

1) Toxin: Heat-STABLE toxin (ST)
2) Mechanism: overactivates GC → ↑cGMP → ↓ resorption of NaCl and H2O in gut

3) Manifestation: watery diarrhea - labile in the Air (AC) but stable on the Ground (GC)

Front 23

Bacillus anthracis exotoxin:
1) Toxin
2) Mechanism
3) Manifestation

Back 23

1) Toxin: edema factor
2) Mechanism: mimics AC enzyme → ↑cAMP
3) Manifestation: likely responsible for characteristic edematous borders of black eschar in cutaneous anthrax

Front 24

Vibrio cholerae exotoxin:
1) Toxin
2) Mechanism
3) Manifestation

Back 24

1) Toxin: cholera toxin - (ADP ribosylating A-B toxin)
2) Mechanism: overactivates Gs → ↑AC → ↑cAMP → ↑Cl- secretion in gut and H2O efflux (same as heat labile toxin of ETEC)
3) Manifestation: voluminous "rice-water" diarrhea

Front 25

Which bacteria release exotoxins that inhibit phagocytic ability?

Back 25

Bordetella pertussis

Front 26

Bordetella pertussis exotoxin:
1) Toxin
2) Mechanism
3) Manifestation

Back 26

1) Toxin: Pertussis toxin - (ADP ribosylating A-B toxin)
2) Mechanism: disables Gi → overactivates AC → ↑cAMP → impairs phagocytosis to permit survival of microbe
3) Manifestation: Whooping Cough (child coughs on expiration and "whoops" on inspiration - toxin may not actually be a cause of cough but can cause the 100 day cough in adults)

Front 27

Which bacteria release exotoxins that inhibit release of NT?

Back 27

- Clostridium tetani
- Clostridium botulinum

Front 28

Clostridium tetani exotoxin:
1) Toxin
2) Mechanism
3) Manifestation

Back 28

1) Toxin: Tetanospasmin
2) Mechanism: protease that cleaves SNARE proteins → prevents release of inhibitory (GABA and glycine) NTs from Renshaw cells in spinal cord
3) Manifestation: spasticity, risus sardonicus, and "lockjaw"

Front 29

Clostridium botulinum exotoxin:
1) Toxin
2) Mechanism
3) Manifestation

Back 29

1) Toxin: Botulinum toxin
2) Mechanism: protease that cleaves SNARE proteins → prevents release of stimulatory (ACh) signals at neuromuscular junctions
3) Manifestation: flaccid paralysis, floppy baby

Front 30

Which bacteria release exotoxins that lyse cell membranes?

Back 30

- Clostridium perfringens
- Streptococcus pyogenes

Front 31

Clostridium perfringens exotoxin:
1) Toxin
2) Mechanism
3) Manifestation

Back 31

1) Toxin: alpha toxin
2) Mechanism: phospholipase (lecithinase) that degrades tissue and cell membranes
3) Manifestation: degrades phospholipids → myonecrosis ("gas gangrene") and hemolysis ("double zone" of hemolysis on blood agar)

Front 32

Streptococcus pyogenes exotoxin:
1) Toxin
2) Mechanism
3) Manifestation

Back 32

1) Toxin: Streptolysin O
2) Mechanism: protein that degrades cell membrane
3) Manifestation: lyses RBCs, contributes to β-hemolysis; host antibodies against toxin (ASO) used to diagnose rheumatic fever (do not confuse w/ immune complexes of poststreptococcal glomerulonephritis)

1) Toxin: Exotoxin A
2) Mechanism: bring MHC II and TCR in proximity to outside of antigen binding site to cause overwhelming release of IFN-γ and IL-2 → shock
3) Manifestation: toxic shock syndrome - fever, rash, shock

Front 33

Which bacteria release exotoxins that are superantigens causing shock?

Back 33

- Staphylococcus aureus
- Streptococcus pyogenes

Front 34

Staphylococcus aureus exotoxin:
1) Toxin
2) Mechanism
3) Manifestation

Back 34

1) Toxin: Toxic Shock Syndrome Toxin (TSST-1)
2) Mechanism: bring MHC II and TCR in proximity to outside of antigen binding site to cause overwhelming release of IFN-γ and IL-2 → shock
3) Manifestation: toxic shock syndrome - fever, rash, shock, other toxins cause scalded skin syndrome (exfoliative toxin) and food poisoning (enterotoxin)

Front 35

Which bacteria have endotoxins? Structure?

Back 35

LPS found in outer membrane of G- bacteria (both cocci and rods)

Front 36

What is the mnemonic to remember traits of Endotoxin?

Back 36

ENDOTOXIN:
- Edema
- Nitric oxide
- DIC / Death
- Outer membrane
- TNF-α
- O-antigen
- eXtremely heat stable
- IL-1
- Neutrophil chemotaxis

Front 37

What are the actions of Endotoxin (especially Lipid A)?

Back 37

- Activates macrophages
- Activates complement
- Activates tissue factor

Front 38

What are the effects of activated macrophages following endotoxin synthesis (especially Lipid A)?

Back 38

- IL-1 → Fever
- TNF → Fever and hypotension
- Nitric Oxide → hypotension

Front 39

What are the effects of activated complement following endotoxin synthesis (especially Lipid A)?

Back 39

- C3a → hypotension and edema
- C5a → neutrophil chemotaxis

Front 40

What are the effects of activated tissue factor following endotoxin synthesis (especially Lipid A)?

Back 40

Coagulation cascade → DIC

Front 41

What are the mechanisms of exchanging genetic material between bacteria?

Back 41

- Transformation
- Conjugation
- Transposition
- Transduction

Front 42

What is Transformation?

Back 42

Ability to take up naked DNA (ie, from cell lysis) from environment (aka "competenence")

Front 43

What is the term for the ability to take up naked DNA (ie, from cell lysis) from environment (aka "competenence")? Which bacteria is this a feature of?

Back 43

Transformation
- S. pneumoniae, H. influenzae type B, and Nesseria (SHiN)
- Any DNA can be used
- Adding deoxyribonuclease to environment will degrade naked DNA in medium → no transformation seen

Front 44

What is Conjugation?

Back 44

Two types:

F+ x F-
- F+ plasmid contains genes required for sex pilus and conjugation
- Bacteria without plasmid are termed F-
- Plasmid (dsDNA) is replicated and transferred through pilus from F+ cell
- No transfer of chromosomal genes

Hfr x F-
- F+ plasmid can become incorporated into bacterial chromosomal DNA, termed high frequency recombination (Hfr) cell
- Replication of incorporated plasmid DNA may include some flanking chromosomal DNA
- Transfer of plasmid and chromosomal genes

Front 45

What is F+ x F- conjugation?

Back 45

- F+ plasmid contains genes required for sex pilus and conjugation
- Bacteria without plasmid are termed F-
- Plasmid (dsDNA) is replicated and transferred through pilus from F+ cell
- No transfer of chromosomal genes

Front 46

What is Hfr x F- conjugation?

Back 46

- F+ plasmid can become incorporated into bacterial chromosomal DNA, termed high frequency recombination (Hfr) cell
- Replication of incorporated plasmid DNA may include some flanking chromosomal DNA
- Transfer of plasmid and chromosomal genes

Front 47

What is Transposition?

Back 47

- Segment of DNA (eg, transposon) that can "jump" (excision and reintegration) from one location to another
- Can transfer genes from plasmid to chromosome and vice versa
- When excision occurs, may include some flanking chromosomal DNA which can be incorporated into a plasmid and transferred to another bacterium
- Eg: antibiotic resistance on R plasmid

Front 48

What happens in Generalized Transduction?

Back 48

- PACKAGING event
- Lytic phage infects bacterium
- Leads to cleavage of bacterial DNA
- Parts of bacterial chromosomal DNA may become packed in viral capsid
- Phage infects another bacterium, transferring these genes

Front 49

What happens in Specialized Transduction?

Back 49

- EXCISION event
- Lysogenic phage infects bacterium
- Viral DNA incorporates into bacterial chromosome
- When phage DNA is excised, flanking bacterial genes may be excised with it
- DNA is packaged into phage viral capsid and can infect another bacterium

Front 50

Which toxins are encoded in a lysogenic phage (specialized transduction)?

Back 50

ABCDE:
- shigA-like toxin
- Botulinum toxin (certain strains)
- Cholera toxin
- Diphtheria toxin
- Erythrogenic toxin of Streptococcus pyogenes