Pathogenesis Flashcards
(41 cards)
Pathogen - ?
Organism that, by its actions, causes harm to its host
Commensal - ?
Benefits from the interaction with host
Host neither benefits nor is harmed
Opportunistic pathogen - ?
Organism that can cause disease in its host given right set of circumstances
- Otherwise commensal
Zoonotic pathogen - ?
Organism with animal reservoir that can be transmitted to humans and cause disease
Define purpose of Koch’s postulates?
What are the postulates? (4 postulates)
- The microorganism must be found in abundance in all organisms suffering from the disease but not in healthy organisms
- The microorganism must be isolated from a diseased organism and grown in pure culture
- The cultured microorganism should cause disease when introduced into a healthy organism
- The microorganism must be re-isolated from the diseased experimental host and identified as being identical to the original causative agent
In what cases does Koch’s postulates not work? (4 cases)
When pathogen secretes something that causes disease symptoms; Organism itself doesn’t need to be present to see disease
When the organism cannot be grown in pure culture; Usually because of complex or unknown nutritional requirements
When growth in the lab leads to loss of virulence; Disease cannot be recapitulated in a model organism
When no animal model is available so in the absence of human experimentation, disease cannot be reproduced in the lab
Traits of strict (professional) pathogens? (5 traits)
Highly adapted organisms for which the pathogenic lifestyle is their main or only option often can’t survive outside of host
Nutritional requirements only satisfied through pathogenesis
Access to a unique niche in the host with little competition from other microorganisms
Transmit very efficiently between hosts
Some are so adapted to the in-host lifestyle that their genome has reduced in size to the point that they can’t live independently
Traits of opportunistic pathogens? (3 traits)
Only cause disease when host defences are compromised e.g. barrier breach, immunocompromisation etc.
When not being a pathogen, they exist as commensals
Inefficiently spread between hosts; Some exceptions
Traits of facultative pathogens? (3 traits)
Majority of pathogens
Well-adapted for multiple lifestyles; Equally at home in niches and when causing disease
Flexibility usually means a larger genome
What is strain variation in context of pathogenesis?
- Use E. coli as example
Not all strains of a particular species will be equally pathogenic, or even pathogenic at all
Most E. coli are harmless commensals
Some have requisite virulence factors and cause human disease; Opportunistic and facultative
Define:
- Pathogenesis
- Pathogenicity
- Virulence
Pathogenesis - Mechanism of disease
Pathogenicity - Ability to cause disease
Virulence - Degree of pathogenicity
What is ID50?
Why is it not necessarily a measure of a pathogens severity?
Dose of bacteria, viruses, or other infective agents that produces infection in 50% of test subjects
A pathogen can have a higher ID50 but cause a more severe disease than one with lower ID50
Virulence factors - ?
Virulence factors of Salmonella enterica? (3 key ones)
Any product of bacterium that contributes to pathogenicity
Colonises mucosal surface
Invades intestinal epithelial cells
Transits to and colonises liver
What 2 factors are bacterium virulence based on?
- What does each rely on?
Invasiveness - Bacterium must get into particular niche and survive there
- Transmissibility
- Adherence/Colonisation
- Evasion of host defences
- Nutrient acquisition
Damage - Bacterium needs to damage host
- Toxins
- Degradative enzymes
Reasons for studying pathogenesis?
Give some examples
Can exploit mechanisms of pathogenicity to treat or prevent infection
e.g. Vaccines, anti-virulence factor therapeutics
How do we study pathogenesis?
2 step process?
Study role of individual proteins/genes and their amino acids and nucleotides
- Phenotypic read out - Measure some property that contributes to virulence
- Study contribution of individual genes/proteins to that phenotype
What does phenotypic read out rely on and why? (hint - strain comparison)
Relies on ability of a pathogen to cause disease in a model species
Animal models allows us to identify and study virulence factors through comparison of different strains with varying pathogenicity
Things to consider when choosing animal models? (3 things)
Ethics, practicality and cost
Alternatives to using animal models (2 alternatives)
Cell lines - Immortalised or primary cell cultures
Organoids - ‘Mini organs’
Traits of Cell lines? (2 traits
Cons? (4 cons)
Less ethical issues
Simpler, cheaper, less variability, easily scalable
Only model a single cell type
Will not mimic disease; Although can model aspects
Immortalised cells often display difference to original tissue
Specialised growth conditions can affect bacterial behaviour
Traits of organoids (3 traits)
Cons? (3 cons)
Less ethical issue
Simpler, cheaper, less variability, easily scalable
Multiple cell types and 3D architecture
Will not mimic disease; Disease is multi-system
Immortalised cells can be different to original tissue
Specialised growth conditions can affect bacterial behaviour
Koch’s Postulates for molecular era (3 postulates) (hint - genes)
- Phenotype under investigation should be associated with pathogenic members of a genus or pathogenic strains of a species
- Specific inactivation of the gene(s) associated with the suspected virulence trait should lead to a measurable loss in pathogenicity or virulence
- Reversion or allelic replacement of the mutated gene should lead to restoration of pathogenicity
How can induction of Gain/loss of function in genes be used to study virulence?
Gain - Over express a gene of interest to see if it enhances or introduces a new phenotype
Loss - Removing or disabling gene to see if pathogen behaves differently without encoded protein
Targeted methods of mutagenesis? (3 methods)
Specific disruption (via insertion) or deletion of target gene
Subtle changes e.g. alter DNA sequence to change structure or function of encoded protein
Homologous recombination is most common tool, but CRISPR-based methods are becoming more common
