Bacterial Pathogens and Diseases I (Exotoxins) Flashcards
Define pathogen.
A microorganism capable of causing disease.
Define pathogenicity.
The ability of an infectious agent to cause disease.
Define virulence.
The quantitative ability of an agent to cause disease.
Define toxigenicity.
The ability of a microorganism to produce a toxin that contributes to the development of disease.
List some virulence mechanisms.
- adherence factors
- biofilms
- invasion of host cells and tissues
- toxins (endotoxins and exotoxins)
What are exotoxins?
- a heterogeneous group of proteins produced and secreted by living bacterial cells
- produced by both gram negative and gram positive bacteria.
- cause disease symptoms in host during disease.
- act via a variety of diverse mechanisms
What selective advantages do exotoxins give to the bacteria?
They may help in transmission of disease; however in severe disease host may be a literal and evolutionary dead end.
However, with many toxins the disease causing activity may be not be the primary function.
Other activities:
- evade immune response
- enable biofilm formation
- enable attachment to host cells.
- escape from phagosomes
All these activities allow for colonisation, niche establishment and carriage - the bacteria has evolutionary
advantage.
Looking at a specific disease, in the case of Staphylococcus aureus, what toxins does it produce and what are their functions?
Haemolytic toxins:
- cause cells to lyse by forming pores
- are an important cause of features of S. aureus disease.
- examples include: α, β, δ, toxins ,Panton Valentine Leukocidin (PVL), LukAB, LukED, LukMF
Phenol soluble modulins (PSM):
- aggregate the lipid bilayer of host cells - lysis
In the case of Staphylococcus aureus, why does it have these toxins?
The α toxins inhibit the attachement of the lysosome to the phagosome, meaning that the S. aureus can survive longer.
PSMs kill off other bacteria, so there is less competition over resources.
They also allow the S aureus to slide acorss surfaces and move, as it is not too motile on its own.
In terms of the infection itself, the α toxin helps in its initial attachment, the β toxin aids in the accumulation of the bacteria, and the PSMs help in the detachment when needed.
Expand on the genetics of exotoxins.
Exotoxins can be encoded by chromosomal genes. Examples:
- Shiga toxin in Shigella dysenteriae
- TcdA & TcdB in C. difficile
Many toxins are coded by extrachromosomal genes.
- plasmids – Bacillus anthracis toxin, tetanus toxin
- lysogenic bacteriophage – e.g. streptococcal pyrogenic exotoxins in Scarlet Fever, Diphtheria toxin.
Describe the classification of exotoxins.
As they are a very diverse group of proteins, there are many ways to classify.
Classification can be by the toxins activity .
- Membrane Acting Toxins – Type I
- Membrane Damaging Toxins – Type II
- Intracellular Toxins – Type III
This classification has its problems:
- many toxins may have more than one type activity.
- as the mechanisms get better understood, this classification tends to break down.
Describe membrane acting toxins – Type I.
ACT: act from without
the cell.
INTERFERE: interfere with host cell signaling by inappropriate activation of host cell receptors.
TARGET: Target receptors include - Guanylyl cyclase → ↑ intracellular cGMP - Adenyl cyclase → ↑ intracellular cAMP - Rho proteins - Ras proteins
Describe membrane damaging toxins – Type II.
They cause damage to the host cell membrane.
- They insert channels into host cell membrane:
- β sheet toxins e.g. S.aureus α – toxin, δ toxin, PVL
- α helix toxins – e.g. diphtheria toxin - Enzymatical damage e.g. S. aureus β- haemolysin
They can either be receptor mediated or receptor independant.
Describe intracellular toxins – Type III.
They are active within the cell – they must gain access to the cell.
They usually have 2 components – AB toxins:
- receptor binding and translocation function – B
- toxigenic (enzymatic) – A
They may be single or multiple B units e.g. Cholera toxin AB(5).
In intracellular toxins, the enzymatic component A has a variety of activities.
List some of them.
- ADP – ribosyl transferases - e.g. Exotoxin A of Pseudomonas aeruginosa, pertussis toxin.
- Glucosyltransferases – e.g. TcdA and TcdB of Clostridium difficile
- Deamidate – e.g. dermonecrotic toxin of Bordetella pertussis.
- Protease – e.g. Clostridial neurotoxins: botulism & tetanus
- Adenylcyclase - e.g. EF toxin of Bacillus anthracis
