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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
What is the role of the A and B in AB toxins of type III
B subunit binds to host cell receptors and delivers A subunit to the cell A subunit has toxic activity
26
What are examples of A subunit toxic activity
ADP-Ribosyltransferase: Diptheria or Cholera Metalloprotease: Botulinum or Tetanus toxin Deadenylation of host 28S rRNA: Shiga toxin
27
What type of bacteria uses ADP-Ribosyltransferase
AB toxin type III protein heat liable diphtheria or cholera
28
What type of bacteria uses Metalloprotease
AB toxin type III protein heat liable Botulinum or Tetanus
29
What type of bacteria uses Deadenylation of host 28S rRNA
AB toxin type III protein heat liable Shiga toxin
30
What are the two primary types of AB toxins
1. single polypeptide: diphtheria and botulinum | 2. multi-subunit: Cholera and Pertussis
31
What type of toxin does diphtheria use and what is the mechanism
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
What type of toxin does cholera use and what is the mechanism
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
What are morphological features of diphtheria and what symptoms does it cause
``` 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
What is the prevention method and treatment for diphtheria
prevention toxoid used for vaccination antibiotics against diphtheria toxin are developed in horses and injected as antitoxin Balto
35
What are the morphological features of Cholera and what symptoms does it cause
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
What are the types of Botulism toxins
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
What are they three types of botulism
food-borne botulism infant botulism wound botulism
38
What is the process of infection for food-borne botulism
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
What is the process of infection for infant botulism
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
What is the process of wound botulism
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
What are the morphological features of Tetanus
``` Clostridium tetani gram + spore forming bacillus obligate anaerobe can grow in wounds ``` causes spastic paralysis get a booster vaccine every 10 years
42
What is the process of the tetanus toxin
cleaves VAMP (synaptobrevin), similar mechanism of action to botulism toxin but it targets inhibitory transmitter
43
What is the super antigen mechanism
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
How are antigens normal processed
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
What transmitter does Tetanus target
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
What transmitter does botulism target
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

Bacterial Diseases (8 decks)

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