Bacterial Toxins Flashcards

1
Q

What are bacterial toxins

A

chemical products produced by an organism which have a poisonous effect on the host

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2
Q

What are historical aspects of bacterial toxins

A

first virulence factors discovered

relatively simple to study

can be modified to make vaccines theses modified toxins are called toxoids

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3
Q

What are toxoids

A

modified toxins to make vaccines

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4
Q

What does the DPT vaccine protect against

A

Diphtheria
Pertussis
Tetanus

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5
Q

What are the role of bacterial toxins

A

toxins have a clear benefit to the bacteria to harm the human host

disrupting cytokine signaling
kill professional phagocytes by Leukocidins
kill cells to release iron and nutrients such as Hemolysins

some cases the toxin evolved for some reason other than harming human hosts

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6
Q

What are three clear ways that toxins benefit the bacteria by preventing host immune defenses

A

disrupt cytokine signaling

produce Leukocidins which kill professional phagocytes

kill cells to release iron and other nutrients such as Hemolysins

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7
Q

What part of bacteria are toxins often associated with

A

extrachromosomal elements such as plasmids and phages via HGT

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8
Q

How are toxins classified

A
I. Nonprotein toxins heat stable
   Endotoxins gram - 
   Trachael cytotoxin 
   Peptidoglycan
   LTA gram +

II. Protein Exotoxins
Type I superantigens
Type II Membrane disrupting toxins
Type III A-B toxins

Type I and II do not enter cells
Type III enter cells

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9
Q

What are the diseases caused by toxins

A

Toxemias: toxin is spread by the flow of blood

Intoxication: caused by ingestion

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10
Q

What are toxemias and what are bacterial examples that cause toxemias

A

the toxin is spread by the flow of blood

Tetanus and Diphtheria

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11
Q

What is Intoxication and what are bacterial examples that use intoxication

A

caused by ingestion

botulism
pre-formed toxins also include some S. aureus and B. cereus enterotxonins (diarrheal and emetic)

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12
Q

What are exotoxins

A

usually target specific organs such as neurotoxins and enterotoxins, etc.

presecene determines tissue specificity

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13
Q

What are endotoxins, how are they classified as toxins

A

only in gram - bacteria, LPS
Lipopolysaccharides, part of the cell wall (the outermost wall) not a released toxin by bacteria

made of lipid A (fatty acids), polysaccharide (inner and outer core), and O-antigen

lipid A molecule is the toxic component

when the macrophage ingest the LPS bacteria and then the bacteria lyses and releases the endotoxins and then the macrophage produces cytokines such as IL-1 and TNF-alpha

the extra cytokines then can enter the blood stream

cell wall activate antibiotics contribute to momentary increase in free LPS due to bacterial lysis

LPS binds to LPS binding protein LPB this complex then bind to the CD14 receptor on the macrophage binding to the TLR4 which causes a release of TNF-alpha, IL-1, IL-6, IL-8, PAF: platelet activating factor

classified as a nonprotein toxin that are heat stable

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14
Q

What is LTA, how is it classified as a toxin

A

gram + Lipoteichoic acid

there are side chain modifications (H, D-Ala, or NAG) that trigger the host response

diglucosyl-diaclglycerol

nonprotein toxin and is heat stable

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15
Q

What are tracheal cytotoxins, how are they classified as toxins

A

Bordetella Tracheal Cytotoxin which is a peptidoglycan fragment

glycopeptide from the peptidoglycan fragments halt ciliary activity and causes the release of IL-1

induces excessive coughing
obligate human pathogen

easier to spread airborne

nonprotein toxin and is heat stable

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16
Q

What are the types of protein exotoxins

A

Heat-labile

Type I superantigens
Type II membrane disrupting toxins
Type III A-B toxins

Type I and II do not enter cells

Type III enters cells

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17
Q

What are type I toxins

A

superantigens

heat liable

do not enter cells

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18
Q

Why are they called super antigens

A

in an antigen presenting cell Class II MHC present an epitope, which is recognized by CD4, this occurs 1:10000 the epitope is specific

in a super antigen the peptide binds to the outside of the MHCII and once the binding occurs it binds to the TCR, independent of the peptide (where the specific epitope usually is) a cytokine is stimulated because of all the T cells that super antigens activate to release cytokines

IL-2 enables the T cell to proliferate

TNF-alpha is the pro-inflammatory response

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19
Q

What causes toxin shock syndrome

A

Cytokine storm from superantigens (type I toxin)

Staphlyococcus and Streptococcus

20
Q

What are type II toxins

What are they used for

What are the types

A

membrane disturbing toxins

can be used to escape from a phagosome LLO, to kill host cells leukocidins, or for nutrient acquisition in the case of hemolysins

pore forming exotoxins
phospholipase exotoxins

heat liable, do not enter cells

21
Q

What are pore-forming toxins and how are they classified as toxins

A

Type II protein toxins
heat liable
do not enter cells

form pores in membranes with proteins composed of alpha helices or beta sheets

22
Q

What are phospholipase exotoxins and how are they classified as toxins

A

Type II protein toxins
heat liable
do not enter cells

also called hemolysin or cytolysis

can cleave the phosphate form the lipid

this cleaving causes the host cell membrane to become unstable this results in cell lysis and cell death

23
Q

What are phospholipase exotoxins and how are they classified as toxins

A

Type II protein toxins
heat liable
do not enter cells

also called hemolysin or cytolysis

can cleave the phosphate form the lipid

this cleaving causes the host cell membrane to become unstable this results in cell lysis and cell death

24
Q

What are Type III toxins and how are they classified

A

Type III protein toxins
heat liable

AB toxins

25
Q

What is the role of the A and B in AB toxins of type III

A

B subunit binds to host cell receptors and delivers A subunit to the cell

A subunit has toxic activity

26
Q

What are examples of A subunit toxic activity

A

ADP-Ribosyltransferase: Diptheria or Cholera

Metalloprotease: Botulinum or Tetanus toxin

Deadenylation of host 28S rRNA: Shiga toxin

27
Q

What type of bacteria uses ADP-Ribosyltransferase

A

AB toxin
type III protein
heat liable

diphtheria or cholera

28
Q

What type of bacteria uses Metalloprotease

A

AB toxin
type III protein
heat liable

Botulinum or Tetanus

29
Q

What type of bacteria uses Deadenylation of host 28S rRNA

A

AB toxin
type III protein
heat liable

Shiga toxin

30
Q

What are the two primary types of AB toxins

A
  1. single polypeptide: diphtheria and botulinum

2. multi-subunit: Cholera and Pertussis

31
Q

What type of toxin does diphtheria use and what is the mechanism

A

Type III AB toxin
protein, heat liable

Diphtheria toxin: single polypeptide toxin

toxin targets EF-2 (diphthamide) which is a modified histamine

when ADP is added it chemically inactivates the protein

ADP-Ribosylates elongation factor 2 blocks ribosome function and the cell dies

This can lead to a pseudomembrane forming over the trachea

32
Q

What type of toxin does cholera use and what is the mechanism

A

Type III AB toxin
protein, heat liable

Cholera toxin is an ADP-Ribosylating

toxin targets Gs protein (Arg)

ADP- Ribosylates causing adenylate cyclase to overactive. cAMP activates ion transport and water follows while trying to maintain osmosis leading to uncontrollable diarrhea

33
Q

What are morphological features of diphtheria and what symptoms does it cause

A
Corynebacterium diphtheria 
aerobic 
non-motile 
non-spore forming 
gram + bacillus 

symptoms
upper respiratory tract infection

fever, malaise, sore throat and appetite loss

a pseudomembrene forms on the pharynx and can potentially block the airway

lymph nodes can also begin to swell

34
Q

What is the prevention method and treatment for diphtheria

A

prevention toxoid used for vaccination

antibiotics against diphtheria toxin are developed in horses and injected as antitoxin

Balto

35
Q

What are the morphological features of Cholera and what symptoms does it cause

A

Vibrio cholera
gram -
comma-shaped bacillus

V. cholera adhere to zooplankton
bacteria attach to small intestine through a type IV pills (TCP) and secrete toxin locally at site of infection of the intestinal attachment

disease manifests as severe dehydration 20L/day

36
Q

What are the types of Botulism toxins

A

BoNT are the botulism toxins

150kDa AB Toxin
A is the light chain and protease

seven different serotypes (A-G) which are phage and plasmid encoded

blocks release of Acetyl-choline Ach toxins, targets the excitatory transmitter

37
Q

What are they three types of botulism

A

food-borne botulism
infant botulism
wound botulism

38
Q

What is the process of infection for food-borne botulism

A
  1. C. botulism in food
  2. spores germinated during processing and bacteria grow in food anaerobically
  3. toxin produce and bacteria die
  4. toxin is ingested
  5. toxin in bloodstream
  6. attacks neurons
  7. causes flaccid paralysis

in homemade canning process

39
Q

What is the process of infection for infant botulism

A
  1. C. botulinum spores are ingested sometimes this is by a child under 2 ingesting honey
  2. spores germinate and C. botulinum grows in the gastrointestinal tract
  3. the toxin is produced
  4. the toxin enters the blood stream
  5. attacks neurons
  6. causes flaccid paralysis

floppy baby syndrome

40
Q

What is the process of wound botulism

A
  1. C. botulinum spores contaminate a wound
  2. spores germinate and C. botulinum grows inside the wound
  3. toxin is produced
  4. toxin is in the blood stream
  5. attacks neurons
  6. induces flaccid paralysis
41
Q

What are the morphological features of Tetanus

A
Clostridium tetani 
gram + 
spore forming bacillus 
obligate anaerobe 
can grow in wounds 

causes spastic paralysis
get a booster vaccine every 10 years

42
Q

What is the process of the tetanus toxin

A

cleaves VAMP (synaptobrevin), similar mechanism of action to botulism toxin but it targets inhibitory transmitter

43
Q

What is the super antigen mechanism

A

superantigen toxin binds directly to the outside of the MHCII and to the outer portion of the T helper cells, TH cells

binds without antigen specificity

2-20% of T cells binding

release of excess amounts of IL-2 and the enter blood circulation instead of the normal localization

can lead to shock, diarrhea, circulation failure, fever

44
Q

How are antigens normal processed

A

MHCII present antigen and only T cells that recognize the antigen are bound and tell B cells to produce antibodies

binds with specificity

normally a localized

1:10000

45
Q

What transmitter does Tetanus target

A

inhibitory transmitter is targeted

the toxin prevents the inhibitory transmitter from working so there is a continuous release os Ach causing the muscles to be continually stimulated

causing spastic paralysis

46
Q

What transmitter does botulism target

A

the excitatory transmitter is targeted

the toxin prevents the excitatory transmitter from firing so no Ach is released so the muscles cannot move

causing flaccid paralysis