Bacterial Pathogens and Disease I Flashcards
Define pathogen, pathogenicity, virulence and toxigenicity
Pathogen: A microorganism capable of causing disease.
Pathogenicity: The ability of an infectious agent to cause disease.
Virulence: The quantitative ability of an agent to cause disease.
Toxigenicity: The ability of a microorganism to produce a toxin that contributes to the development of disease.
What are the mechanisms of virulence?
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.
Produced by both gram negative and gram-positive bacteria.
Cause disease symptoms in host during disease.
Act via a variety of diverse mechanisms.
Why do bacteria have exotoxins?
Cause disease? – may help 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 allowing for colonisation, niche establishment and carriage - Evolutionary advantage.
What toxins does Staphylococcus aureus utilise?
Haemolytic toxins
- cause cells to lyse by forming pores
- Important cause of features of S. aureus disease.
- α,β,γ, toxins ,Panton Valentine Leukocidin (PVL), LukAB, LukED, LukMF
Phenol soluble modulins PSM
- Aggregate the lipid bilayer of host cells - lysis
Majority of S. aureus in humans is asymptomatic carriage in the nose.
Why does S. aureus have exotoxins?
PSMs allow bacteria to escape from the lysosomes
Alpha toxins blocks the binding of lysosomes to the phagosome
The PSM of staph aureus is really useful at killing other bacteria in the environment
Staph aureus cannot move, but releases PSM as it allows it to slide through certain media
Alpha and beta toxins especially help initiate the formation of biofilms, a community of bacteria, which can then interact with other molecules to form a secondary structure
PSM then helps chunks of that biofilm to move and then aids carriage
How are exotoxins encoded?
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.
What are the classifications of exotoxins? What is the problem with this system?
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
This classification has its problems –
- Many toxins may have more than one type activity.
- As mechanisms better understood this classification tends to break down.
What are the characteristics of Type I exotoxins?
Act: - Act from without the cell Interfere: - Interfere with host cell signalling by inappropriate activation of host cell receptors Target: - Target receptors include: · Guanylyl cyclase → ↑ intracellular cGMP · Adenyl cyclase → ↑ intracellular cAMP · Rho proteins · Ras proteins
Give an example of a Type I exotoxin and what it does?
E. coli Stable Heat Toxin
Basically you have the heat stable E coli toxin binding to the CGC receptor leading to an increased production of cGMP which acts on protein kinases or the cystic fibrosis transmembrane receptor that affect an ion pump that controls the balance of chloride and bicarbonate ions
So now you have dysregulated secretion of chloride and bicarbonate ions and a knock on effect on the control of the proton-sodium pump
This leads on to a dysregulated secretion of sodium ions outside the cell, what follows? Water
Ergo diarrhoea
What are the characteristics of Type II exotoxins?
Cause damage to the host cell membrane
1. Insert channels into host cell membrane.
- β sheet toxins e.g. S.aureus α – toxin, γ toxin, PVL
- α helix toxins – e.g. diphtheria toxin
2. Enzymatical damage e.g. S. aureus β- haemolysin, PSM
OR considered
1. Receptor mediated
2. Receptor Independent
What are the characteristics of Type III exotoxins?
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
What are Type III AB toxins and what enzymatic components do they have?
Intracellular toxins- Type III- AB toxins
Enzymatic component A – wide variety of activities.
- ADP – ribosyl transferases - e.g. Exotoxin A of Pseudomonas aeruginosa, pertussis toxin.
- Glucosyltransferases – e.g. TcdA and TcdB of Clostridium difficile
- Deamidase – e.g. dermonecrotic toxin of Bordetella pertussis.
- Protease – e.g. Clostridial neurotoxins: botulism & tetanus
- Adenylcyclase - e.g. EF (Edema factor) toxin of Bacillus anthracis
What are the other two intracellular toxins?
Type III secretion and toxin injection
- Multi-molecule complexes that act like needles
- E.g. YopE in Yersinia species
Type IV secretion and toxin injection
- A multimeric secretory system that acts like a pump
- E.g. CagA in Helicobacter pylori
How can exotoxins induce inflammatory cytokines release?
IL1, IL1β, TNF, IL 6, interferon γ, IL18
Mechanisms:
- Superantigen – non specific bridging of the MHC Class II and T- cell receptor leading to cytokine production. E.g. Staphylococcal Exfoliative Toxin A, Toxic Shock Syndrome Toxin 1 (TSST1)
- Via activation of the different inflammasome leading to release IL1 β and IL18 e.g. S. aureus toxin A, PVL.
