Bacterial Pathogens and Diseases I (Exotoxins) Flashcards
What is a pathogen?
A microorganism capable of causing disease
What is pathogenicity?
The ability of an infectious agent to cause disease
What is virulence?
The quantitative ability of an agent to cause diseas
What is meant by toxigenicity?
The ability of a microorganism to produce a toxin that contributes to the development of disease
What are the 4 virulence mechanisms?
- Adherence Factors
- Biofilms
- Invasion of Host Cells + Tissues
- Toxins; endotoxins + exotoxins
How are virulence mechanisms obtained?
These factors are genetically acquired in the bacterial genome allowing them to be virulent
What are exotoxins?
Heterogeneous group of proteins produced and secreted by living bacterial cells
What type of bacteria produces exotoxins?
Produced by both gram negative and gram positive bacteria
What is the effect of exotoxins on the human body?
Cause disease symptoms in hosts during disease by acting via a variety of diverse mechanisms
What are the selective advantages exotoxins provide for bacteria?
Ability to cause disease
However with many toxins the disease causing activity may not be the primary function
How do exotoxins enable bacteria to cause disease?
May help transmission of disease, however in severe disease the host may be a literal and evolutionary dead end
What are other exotoxin activities in bacteria?
- Evade immune response
- Enable biofilm formation
- Enable attachment to host cells
- Escape from phagosomes
What is the effect of exotoxins on bacterial survival?
All allowing for colonisation, niche establishment and carriage - Evolutionary advantage
How do haemolytic toxins cause S. aureus?
Haemolytic toxins cause cells to lyse by forming pores
Important cause of features of S. aureus disease
Name examples of haemolytic toxins leading to S. aureus
- α,β,δ, toxins
- Panton Valentine Leukocidin (PVL)
- LukAB
- LukED
- LukMF
How do Phenol soluble modulins cause staphylococcus aureus?
PSM aggregate the lipid bilayer of host cells - lysis
How does S.aureus most commonly present in humans?
Majority of S. aureus in humans is asymptomatic carriage in the nose
How does S.aureus survive in the human body?
S.aureus colonises our nose in a biofilm
S.aureus’ toxins allow this commensalism biofilm to exist on our nasopharyngeal mucosal surfaces
Describe the structure of S.aureus biofilms in the nose
These biofilms are populations of bacteria that exist as complex structures that build up into layers and acquire different components
Outline how S.aureus infects
- Phagocytosis of invading bacteria
- Normally phagosome fusion to lysosome
⇒ bacteria destruction - S. aureus α + PSM toxins inhibit lysosome fusing
- Enables bacteria to escape phagosome into cytoplasm
⇒ intracellular niche establishment + replication - PSM toxins target cohabiting bacterial species within
established niches, aiding competition for resources
Describe the genetics of exotoxins
Can be encoded by chromosomal or extra-chromosomal genes
Give examples of chromosomal genes encoding exotoxins
- Shiga toxin in Shigella dysenteriae
- TcdA & TcdB in C. difficile
What extrachromosomal genes encode exotoxins?
Plasmids
- Bacillus anthracis toxin
- Tetanus toxin
Lysogenic bacteriophage
- Streptococcal pyrogenic exotoxins in Scarlet Fever
- Diphtheria toxin.
What is a plasmid?
Small circular DNA, separate from chromosomes that is passed on between bacteria through conjugation, transfection and transduction
What is a bacteriophage?
Virus that infects bacteria and takes up some of its genes to pass on to the next bacteria the virus infects via transduction
How do streptococcus strains lead to scarlet fever?
Streptococcus strains normally cause a sore throat or tonsillitis but certain toxigenic streptococcus strains that have been lysogenically converted now can cause scarlet fever
What is meant by lysogenic conversion of pathogens?
When bacteria is infected by a phage carrying a gene encoding a haemolytic toxin into the strain
What is the most common way of classifying exotoxins?
As a very diverse group of proteins and many ways to classify e.g. toxin activity
What are the 3 classifications of exotoxin activity?
Type I
- Membrane Acting Toxins
Type II
- Membrane Damaging Toxins
Type III
- Intracellular Toxins
What are the drawbacks of classifying exotoxins based on activity?
Many toxins may have more than one type activity
As mechanisms better understood this classification tends to break down
What type of toxin do Type I (membrane acting) bacteria produce?
These bacteria produce toxins that can bind to a signalling receptor on the cell
What is the effect of Membrane acting toxins?
As a result of ligand-receptor interaction, a wide range of intracellular signalling cascades are activated that cause damage to the intracellular metabolic processes occurring
Which receptors are targeted by Type I toxins?
- Guanalyl cyclase
- Adenyl cyclase
- Rho protein
- Ras protein
What is the normal efefct of guanalyl and adenyl cyclase?
Gunalyl and Adenyl cyclase are GTPase receptor molecules increase intracellular cGMP
What is the normal physiological role of Rho and Ras proteins?
Rho and Ras are smaller receptor proteins that are enzymes that generate cAMP to control actin and microtubule filaments
What is GC-C?
GC-C is a key receptor in regulating the electrolyte level and fluidity of intestinal content