Bacterial Toxins Flashcards
What are bacterial toxins
chemical products produced by an organism which have a poisonous effect on the host
What are historical aspects of bacterial toxins
first virulence factors discovered
relatively simple to study
can be modified to make vaccines theses modified toxins are called toxoids
What are toxoids
modified toxins to make vaccines
What does the DPT vaccine protect against
Diphtheria
Pertussis
Tetanus
What are the role of bacterial toxins
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
What are three clear ways that toxins benefit the bacteria by preventing host immune defenses
disrupt cytokine signaling
produce Leukocidins which kill professional phagocytes
kill cells to release iron and other nutrients such as Hemolysins
What part of bacteria are toxins often associated with
extrachromosomal elements such as plasmids and phages via HGT
How are toxins classified
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
What are the diseases caused by toxins
Toxemias: toxin is spread by the flow of blood
Intoxication: caused by ingestion
What are toxemias and what are bacterial examples that cause toxemias
the toxin is spread by the flow of blood
Tetanus and Diphtheria
What is Intoxication and what are bacterial examples that use intoxication
caused by ingestion
botulism
pre-formed toxins also include some S. aureus and B. cereus enterotxonins (diarrheal and emetic)
What are exotoxins
usually target specific organs such as neurotoxins and enterotoxins, etc.
presecene determines tissue specificity
What are endotoxins, how are they classified as toxins
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
What is LTA, how is it classified as a toxin
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
What are tracheal cytotoxins, how are they classified as toxins
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
What are the types of protein exotoxins
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
What are type I toxins
superantigens
heat liable
do not enter cells
Why are they called super antigens
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
What causes toxin shock syndrome
Cytokine storm from superantigens (type I toxin)
Staphlyococcus and Streptococcus
What are type II toxins
What are they used for
What are the types
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
What are pore-forming toxins and how are they classified as toxins
Type II protein toxins
heat liable
do not enter cells
form pores in membranes with proteins composed of alpha helices or beta sheets
What are phospholipase exotoxins and how are they classified as toxins
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
What are phospholipase exotoxins and how are they classified as toxins
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
What are Type III toxins and how are they classified
Type III protein toxins
heat liable
AB toxins
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
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
What type of bacteria uses ADP-Ribosyltransferase
AB toxin
type III protein
heat liable
diphtheria or cholera
What type of bacteria uses Metalloprotease
AB toxin
type III protein
heat liable
Botulinum or Tetanus
What type of bacteria uses Deadenylation of host 28S rRNA
AB toxin
type III protein
heat liable
Shiga toxin
What are the two primary types of AB toxins
- single polypeptide: diphtheria and botulinum
2. multi-subunit: Cholera and Pertussis
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
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
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
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
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
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
What are they three types of botulism
food-borne botulism
infant botulism
wound botulism
What is the process of infection for food-borne botulism
- C. botulism in food
- spores germinated during processing and bacteria grow in food anaerobically
- toxin produce and bacteria die
- toxin is ingested
- toxin in bloodstream
- attacks neurons
- causes flaccid paralysis
in homemade canning process
What is the process of infection for infant botulism
- C. botulinum spores are ingested sometimes this is by a child under 2 ingesting honey
- spores germinate and C. botulinum grows in the gastrointestinal tract
- the toxin is produced
- the toxin enters the blood stream
- attacks neurons
- causes flaccid paralysis
floppy baby syndrome
What is the process of wound botulism
- C. botulinum spores contaminate a wound
- spores germinate and C. botulinum grows inside the wound
- toxin is produced
- toxin is in the blood stream
- attacks neurons
- induces flaccid paralysis
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
What is the process of the tetanus toxin
cleaves VAMP (synaptobrevin), similar mechanism of action to botulism toxin but it targets inhibitory transmitter
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
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
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
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
