Bacterial Pathogens and Diseases I - Exotoxins Flashcards
What is a pathogen?
β A microorganism capable of causing disease
What is pathogenicity?
β The ability of an infectious agent to cause disease
What is virulence?
β The quantitative ability of an agent to cause disease
What is toxigenicity?
β The ability of a microorganism to produce a toxin that contributes to development of disease
what are 4 virulence mechanisms?
β Adherence factors
β biofilms
β invasion of host cells
β toxins
What are endotoxins?
β a heterogenous group of proteins produced and secreted by living bacterial cells
What types of bacteria produce endotoxins?
β gram negative and gram positive
What selective advantages do exotoxins give to the bacteria?
β they cause disease that may help transmission
What are the 4 other actions of toxins?
β Evade immune response
β Enable biofilm formation
β Enable attachment to host cells
β Escape from phagosomes
What do toxins allow for?
β Colonisation
β Niche establishment and carriage
What are the two proteins S.Aureus uses to cause disease?
β Haemolytic toxins
β Phenol soluble modulins (PSM)
What are the 7 haemolytic toxins of S.Aureus?
β Alpha β beta β delta β Panton valentine leukocidin (PVL) β LukAB β LukED β LukMF
What is the effect of haemolytic toxins?
β cause cells to lyse by forming pores
What is the function of phenol soluble modulins?
β aggregate the lipid bilayer of host cells
Where is the majority of S.Aureus?
β asymptomatic carriage in the nose
How does S.aureus remain alive in the cell?
β alpha toxin and PSM prevent the attachment of the lysosome to the phagosome so the bacteria can remain alive in the cell
What does PSM allow S.aureus to do?
β allows S. aureus to slide across surfaces
β because S.aureus is not motile
What toxin enables the attachment of a biofilm?
β Alpha toxin
What toxins enable the growth of a biofilm?
β beta toxin and PSM
What effect does PSM have on the biofilm?
β Allows it to detach and spread
What can toxins be encoded by?
β chromosomal genes
β extrachromosomal genes
β plasmids
βlysogenic bacteriophage
What bacteria have toxins encoded for by plasmids?
β Anthtrax
β tetanus
What are the three classifications of exotoxins?
β Membrane acting toxins - type I
β membrane damaging toxins - type II
β intracellular toxins - type III
What is the main issue with the classification of exotoxins?
β many toxins have more than one type of activity
What are 4 targets of membrane acting toxins (type 1) ?
β guanylyl cyclase
β adenylyl cyclase
β Rho proteins
β Ras proteins
Describe how the E.Coli heat stable toxin works and how it causes diarrhoea?
β Binds to a specific receptor (GC - C)
β causes the intracellular domain to produce cGMP
β cGMP acts on a pump inside the cell membrane (CFTR)
β the CFTR normally pumps Cl- and HCO3- ions out of the cell
β by stimulating CFTR it pumps out more
β it produces cAMP that inhibits a pump that brings in Na+ and pumps out H+
β Na+ and Cl- ions are salt so when they move out of the cell water follows them
β Diarrhoea occurs
What type of toxin is the E.Coli heat stable toxin?
β Type I exotoxin
What do type 1 toxins interfere with?
β Host cell signaling by inappropriate cell activation of host cell receptors
What are the two effects of Type II (membrane damaging) toxins?
β Inserting channels into the host cell membrane
β enzymatic damage
Describe how alpha toxin works?
β binds to a receptor called ADAM10
β it polymerises to form channels
βthis allows cells to be damaged
βintracellular components move out
What is the structure of intracellular toxins?
β usually have two components (A and B)
What do the components of intracellular toxins do?
βA - toxigenic
β B - receptor binding and translocation
What is the structure of the cholera toxins?
β’ AB5
What are 5 examples of intracellular toxins?
β’ ADP β’ Glucosyltransferases β’ Deamidate β’ Protease β’ Adenylyl cyclase
What is an example of a deamidate toxin (type III) ?
β’ Dermonecrotic toxin of bordetella pertussis
What is an example of a protease toxin (type III)?
β’ Clostridial neurotoxins : botulism and tetanus