Bacterial Pathogens and Diseases I (Exotoxins) Flashcards
Pathogen - define
Pathogen: A microorganism capable of causing disease.
Pathogenicity - define
Pathogenicity: The ability of an infectious agent to cause disease.
Virulence - define
Virulence: The quantitative ability of an agent to cause disease.
Toxigenicity - define
Toxigenicity: The ability of a microorganism to produce a toxin that contributes to the development of disease.
Virulence – Mechanisms - list
Adherence Factors
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.
Exotins - produced by what
Produced by both gram negative and gram positive bacteria.
Exotins - effect
Cause disease symptoms in host during disease.
Cause disease? – may help transmission of disease, however in severe disease host may be a literal and evolutionary dead end.
Exotins - action
Act via a variety of diverse mechanisms.
What selective advantages do exotoxins give to the bacteria?
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 allowing for colonisation, niche establishment and carriage - Evolutionary advantage.
Haemolytic toxins - effect, involved in which disease and give examples
Haemolytic toxins:
cause cells to lyse by forming pores
Important cause of features of S. aureus disease.
α,β,δ, toxins ,Panton Valentine Leukocidin (PVL), LukAB, LukED, LukMF
Describe genetic encoding of exotins
Can be encoded by chromosomal genes Shiga toxin in Shigella dysenteriae, TcdA & TcdB in C. difficile
Many toxins coded by extrachromosomal genes:
Plasmids – Bacillus anthracis toxin, tetanus toxin
Lysogenic bacteriophage – e.g. streptococcal pyrogenic exotoxins in Scarlet Fever, Diphtheria toxin.
Classification of Exotoxins
As very diverse group of proteins and 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
Problems with classification of Exotoxins
This classification has its problems –
Many toxins may have more than one type activity.
As mechanisms better understood this classification tends to break down.
Membrane Acting toxins – Type I, describe where they:
- Act
- Interfere
- Target
- 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
Membrane damaging toxins – type II - describe and explain action
Cause damage to the host cell membrane.
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, PSM
OR
Receptor mediated
Receptor Independent
Membrane Damaging Toxins - describe action
Soluble monomer
Membrane associated monomer binding to specific receptor – ADAM10 - a sheddase a disintegrin and metalloproteinase
Nascent oligomer/pre pore complex
Membrane insertion
Intracellular toxins – type III - action
Active within the cell – must gain access to the cell
Usually 2 components – AB Toxins
- Receptor binding and translocation function – B
- Toxigenic (enzymatic) – A
- May be single or multiple B units e.g. Cholera toxin AB5
