Bacterial pathogens and disease - exotoxins Flashcards
What is a pathogen?
= a microorganism capable of causing disease
What is pathogenicity?
= the ability of an infections agent to cause disease
What is virulence?
= the quantitative ability of an agent to cause disease
What is toxigenictity?
= the ability of a microorganism to produce a toxin that contributes to the development of disease
What are the mechanisms for pathogenesis?
- Adherence factors - allowing bacteria to bind/attach to cells
- Biofilms - forms when microorganism adhere to the surface of some object in a moist environment and begin to reproduce.
- Invasion of host cells and tissues
- Toxins - endotoxins and exotoxins
What are exotoxins?
= toxins produced and secreted by living bacterial cells into the surroundings
- Produced by both gram negative and gram positive bacteria
- Cause disease symptoms in host during disease
What are the selective advantages of exotoxins?
- Evade immune response
- Enable biofilm formation
- Enable attachment to host cells
- Escape from phagosomes
They all allow for colonisation, niche establishment and carriage advantage
Give an example of host-pathogen interaction:
Staphylococcus aureus
- have haemolytic toxins which cause cells to lyse by forming pores in the membrane
- Phenol soluble modulins (PSM) aggregate the lipid bilayer of host cells - causing lysis
How can exotoxins be encoded?
by chromosomal genes
Many toxins are coded by extrachromosomal genes like plasmids
How can you classify exotoxins?
Very diverse group, so you have to classify them by their activity
- Membrane acting toxins - type 1
- Membrane damaging toxins - type 2
- Intracellular toxins - type 3
*but many toxins have more than one type of activity, as we know more about toxins, this classification becomes less realistic
Describe membrane acting toxins - type 1
- Bind surface receptors
- Stimulates transmembrane signals
- Interfere with host cell signalling by interrering with activation of host cell receptors, eg.:
- guanylyl cyclase to increase cGMP
- adenyl cyclase to increase intracellular cAMP - gives the potential to cause severe disease
Describe membrane damaging toxins - type 2
- Cause damage to the host cell membrane
- Insert channels into host cell membrane –> cell lysis
- Causing enzymatical damage
- Insert channels into host cell membrane –> cell lysis
Either Receptor mediated or receptor independent:
Describe intracellular toxins - type 3
Active within the cell - must gain access to the cell
2 components - AB toxins
- Component B - binds to cell surface receptor to allow for internalisation of the toxin
- Component A - toxigenic within the cell and has enzymatic activity
- ADP - ribosyl transferases
- Glucosyltransferases
- Deamidase
- Protease
How do the toxins interact with the immune system?
Exotoxins are able to induce inflammatory cytokine release by 2 mechanisms:
- Superantigens = non-specific bridging of MHC Class II and T cell receptor leading to cytokine production - lead to toxic shock syndrome (eg. from contaminated tampon)
- via activation of different inflammasomes (signalling pathways to detect infection and damage) leading to release of IL1 B and IL18
What are toxoids?
= inactive proteins but still highly immunogenic - form the basis for vaccines (tetanus, diphtheria)
- Toxins can be inactivated using formaldehyde to produce toxoids
