Microbial Toxins II (deets)

Question 1

Lipopolysaccharides (LPS) of gram negative bacteria were first called _______ to indicate their association with bacterial cells. LPS is an example of a _______ that is recognized by the innate immune system and elicits host responses by a pathway that involves ___(4)___

Answer 1

• “endotoxin”
• pathogen-associated molecular pattern (PAMP)
• LPS binding protein, CD14, TLR4, and other signal transduction molecules

Question 2

The superantigens are the most potent known _______. They act by binding both to _______ and to _______, and they activate much larger numbers of T cells than any specific antigen does. Superantigens stimulate excessive production of _______, thereby causing pathologic effects

Answer 2

• T cell activators
• major histocompatibility (MHC) class II molecules on antigen-presenting cells
• specific Vβ chains on T cells at a site that is different from the antigen-binding site
• cytokines (including interleukin-2, interferon gamma, and others)

Question 3

Diphtheria toxin and Pseudomonas aeruginosa exotoxin A inactivate _______, which is required for peptide chain elongation. They are both ADP ribosyltransferases that transfer _______ from nicotinamide adenine dinucleotide (NAD) to a modified histidine residue called diphthamide on EF-2, thereby _______

Answer 3

• elongation factor 2 (EF-2)
• adenosine diphosphate ribose (ADP-ribose)
• inactivating EF-2 in the cytoplasm

Question 4

Diphtheria toxin and Pseudomonas aeruginosa exotoxin A inactivate elongation factor 2 (EF-2), which is required for peptide chain elongation. They are both ADP ribosyltransferases that transfer adenosine diphosphate ribose (ADP-ribose) from _______ to _______, thereby inactivating EF-2 in the cytoplasm

Answer 4

• nicotinamide adenine dinucleotide (NAD)

- a modified histidine residue called diphthamide on EF-2

Question 5

Shiga toxins of Shigella dysenteriae and E. coli, and the plant toxin ricin, are _______ that remove one particular adenine residue from the ____ RNA of the ____ ribosomal subunit, thereby _______

Answer 5

• highly specific RNA N-glycosidases
• 28S
• 60S
• inactivating the ribosomes

Question 6

Heat-labile enterotoxins of Vibrio cholerae and Escherichia coli are _______ that increase cell membrane-associated adenylate cyclase activity by ADP-ribosylating and activating the _______ of the cyclase complex. Increased intracellular cAMP in small intestinal enterocytes causes active chloride secretion and results in _______

Answer 6

• ADP ribosyltransferases
• α subunit of the stimulatory Gs regulatory protein
• secretory diarrhea

Question 7

Heat-labile enterotoxins of Vibrio cholerae and Escherichia coli are ADP ribosyltransferases that _______ by ADP-ribosylating and activating the α subunit of the stimulatory Gs regulatory protein of the cyclase complex. Increased _______ in small intestinal enterocytes causes active _______ secretion and results in secretory diarrhea

Answer 7

• increase cell membrane-associated adenylate cyclase activity
• intracellular cAMP
• chloride

Question 8

Pertussis toxin is an ADP ribosyltransferase that increases _______ by ADP-ribosylating and inactivating the __ subunit of the inhibitory ___ regulatory protein of the cyclase complex. Increased _______ causes tissue-specific effects.

Answer 8

• cell membrane-associated adenylate cyclase activity
• α
• Gi
• intracellular cAMP

Question 9

Heat-stable enterotoxin I (ST-I) of E. coli activates _______. Increased intracellular cGMP in enterocytes also causes _______.

Answer 9

• cell membrane-associated guanylate cyclase

- secretory diarrhea

Question 10

Heat-stable enterotoxin I (ST-I) of E. coli activates cell membrane-associated guanylate cyclase. Increased ________ also causes secretory diarrhea.

Answer 10

intracellular cGMP in enterocytes

Question 11

Anthrax edema factor (EF) from Bacillus anthracis and adenylate cyclase toxin from Bordetella pertussis are _______ that enter target cells, cause intracellular cAMP to _______, and produce _______. Their enzymatic activity requires activation by _______ and _______, which are provided by the target cells

Answer 11

• adenylate cyclases
• increase
• cAMP dependent effects
• calmodulin
• calcium

Question 12

Anthrax lethal factor (LF) is an endopeptidase that _______.

Answer 12

-cleaves several MAP kinase kinase proteins and inactivates their function in signal transduction

Question 13

Clostridium difficile toxins A and B are glucosyl transferases that _________.

Answer 13

alter the actin cytoskeleton of target cells by transferring glucose from UDP-glucose to several Rho family GTPases (including Rho, Rac and Cdc42), thereby inactivating them

Question 14

Botulinum toxin (7 antigenic types, A-G) causes flaccid paralysis of skeletal muscles by _______. Types ___(3)___ most often cause disease in humans

Answer 14

• inhibiting release of acetylcholine at myoneural junctions

- A, B and E

Question 15

Tetanus toxin (1 antigenic type) causes sustained muscular contraction (spastic paralysis/tetany) of skeletal muscles by

Answer 15

inhibiting the release of neurotransmitter from inhibitory interneurons in the spinal cord

Question 16

Tetanus toxin and the botulinum toxins are zinc-dependent endopeptidases that inactivate ___(3)___. Each toxin cleaves one specific protein at one specific site, and the individual serotypes of botulinum toxin differ in specificity from one another.

Answer 16

-specific SNARE proteins required for neuroexocytosis [VAMP (also called synaptobrevin), the 25 kDa synaptosome-associated protein (SNAP-25), and syntaxin]

Question 17

Botulinum toxin is used therapeutically to treat several _______ and _______, including _______ and _______. It is also widely used for cosmetic effects

Answer 17

focal dystonias and involuntary movement disorders, including strabismus and blepharospasm