Bacterial Pathogens and Diseases I (Exotoxins) Flashcards
what is a pathogen?
a microorganism capable of causing disease
what is meant by pathogenicity?
the ability of an infectious agent to cause disease
what is meant by virulence?
the quantitative ability of an agent to cause disease
what is meant by toxigenicity?
the ability of a microorganism to produce a toxin that contributes to the development of disease
what are virulence factors?
Factors that bacteria have genetically acquired and encoded in their genome. They are necessary for the bacteria to undergo the process that leads to disease
examples:
adherence factors (to get into tissues)
biofilms
invasion of host cells and tissues
toxins – endotoxins and exotoxins
what are exotoxins?
Heterogeneous group of proteins produced and secreted by living bacterial cells into the host tissues, causing disease symptoms
Produced by both gram negative and gram positive bacteria
What selective advantages do exotoxins give to the bacteria?
help cause disease
Evade immune response Enable biofilm formation Enable attachment to host cells. Escape from phagosomes Allowing carriage without disease
example of toxins
Haemolytic toxins and Phenol soluble modulins
where is s. aureus in our body?
commensal in our nasal cavity – it isn’t doing any damage or releasing toxins
how does s. aureus colonise?
in a bio film
PSMs give it gliding properties – useful for when it lives in the nose. Also contains toxins that prevent that phagolyosome fusion and therefore prevent bacteria death. PSM allows bacteria to escape from the early phagosome.
Haemolytic toxins to damage other organisms and prevent them from growing – bacteria are in competition, need to kill off other bacteria so they can grow.
Haemolytic toxins
cause cells to lyse by forming pores
Important cause of features of S. aureus disease.
Phenol soluble modulins
interfere with and aggregate the lipid bilayer of host cells, leading to lysis
bacterial chromosome?
single circular piece of double stranded DNA
where are toxin genes encoded?
most toxin genes are encoded on the chromosome, but not all of them - many toxins coded by extrachromosomal genes (plasmids)
how do bacteria exchange genetic information?
conjugation, transduction and transfection
plasmids play a role
what are plasmids?
plasmids are independently replicating small pieces of circular DNA that exist in the bacteria separate from the chromosome, can be passed onto other bacteria via conjugation, transduction and transfection – this is partly how bacteria exchange genetic information
explain transfection
toxins can be transferred from 1 bacteria to another via bacteriophages
a bacteriophage is a virus that infects a bacteria, and as a result it picks up some of the genes in the bacteria, and transfers it to the next bacteria it infects
Classification of Exotoxins
- Membrane Acting Toxins – Type I
- Membrane Damaging Toxins – Type II
- Intracellular Toxins – Type III
Membrane Acting toxins – Type I
act - on the outside of cells or on the membrane
interfere - host cell signaling by inappropriate activation of host cell receptor
target receptors:
- Guanylyl cyclase, increase intracellular cGMP
- Adenyl cyclase, increase intracellular cAMP
- Rho and Ras proteins (enzymes involved in generating GTP)
an example of a type 1 membrane acting toxin
ecoli, produces an STa toxin
once STa engages with the receptor, it causes an increase in cGMP
Membrane Damaging toxins – Type II
cause damage to the host cell membrane
- insert channels into host cell membrane (beta sheet or alpha helix toxins)
- enzymatical damage
Receptor mediated or Receptor Independent
explain the difference between receptor mediated and receptor independent (type II membrane damaging toxins)
receptor mediated is where a toxin binds to the toxic specific receptor, and defined (hexametric or octametric) pores forms (alpha toxins)
receptor independent is where the toxin attaches itself to the membrane and causes it to disintegrate, and there are formation of short lived pores (many alpha type PSM’s)
Intracellular toxins – type III
these toxins go inside cells
2 components: A and B
A part- activity, toxigenic and enzymatic
B part- receptor binding and translocation function
May be single or multiple B units e.g. Cholera toxin AB5. 5 binding subunits: Active domain sitting on the top.
Once the toxin is inside the cell, it releases the A part which has biological activity, usually involves some sort of enzymatic degradation.
The protein is held together by electrostatic attractions, meaning its usually susceptible to heat. On the other hand if it’s a single polypeptide chain, heat will not affect or inactivate it.
Another type of type III toxin squirts effector proteins to disrupt the cell
the enzymatic component A of Type III toxins has a wide variety of activities - give some examples:
ADP – ribosyl transferases - e.g. Exotoxin A of Pseudomonas aeruginosa, pertussis toxin.
Glucosyltransferases – e.g. TcdA from Clostridium difficile, modifies ribosomal RNA so protein synthesis doesn’t happen efficiently
Deamidase – e.g. dermonecrotic toxin of Bordetella pertussis.
Protease – e.g. Clostridial neurotoxins: botulism & tetanus, damage to presynaptic vesicles on neuromuscular junction or in the brain
Adenylcyclase - e.g. EF toxin of Bacillus anthracis
