Virulence and virulence factors Flashcards
(18 cards)
What is pathogenesis?
mechanism of disease
What is pathogenicity?
ability to cause disease
What is virulence?
degree of pathogenicity
LD50
dose needed to kill 50% sample
(LD = lethal dose)
ID50
dose to infect 50% sample
What are the limitations of LD50 and ID50?
-measured in model systems, not necessarily same in humans
-reflect cumulative contribution of many steps within disease process
-values can be misleading (ie. severity of disease not reflected)
What alters bacteria virulence?
-invasiveness of the bacteria (whether it can get into niche and survive and replicate there) (transmissibility, adherence, nutrient acquisition, etc)
-damage bacteria causes (toxins, enzymes)
What are virulence factors?
bacterial products that contribute to pathogenicity
-lots of virulence involved in pathogenicity (diff factors in diff steps)
How can pathogenesis be studied?
phenotypic readouts (measuring a property, eg. toxin acitivity)
studying gene contribution to that phenotype
How can phenotypic readouts be used to study pathogenesis?
-use model organism (typically mouse, etc -must choose ethically, practically and cost-efficiently) to observe disease (may be diff sim species or diseases)
-identify and study virulence factors
What alternatives are there to using animal models to study pathogenesis phenotypically?
-cell lines (simpler, more ethical, but only shows one cell line so doesn’t mimic whole disease) -> used to study adherence, invasion, toxicity
-organoids (simpler, more ethical, can show multiple cell types and 3D architecture, doesn’t mimic whole disease
What tools can be used to study virulence factors?
-using immunological tools, like antibodies against specific proteins
-using biochem tools, such as purifying protein and observing phenotype
-using genetic tools -over-expressing or knocking out genes (gain or loss of funct observed)
How can targetted mutagenesis be carried out?
-specific disruption (insertion into ORF)
-specific deletion of target gene
-subtler changes: alter DNA seq
How can random mutagenesis be carried out?
-chem mutageneis
-radiation
-transposons
What are the advantages of using cell lines to study pathogenesis?
-less ethical issues
-simpler, cheaper, easier to scale, more variable
What are the disadvantages of using cell lines to study pathogenesis?
-only model 1 cell line
-only mimics aspects of disease
-immortalised cell lines different to original tissue
-specialised growth conditions affect bact behaviour
What are the advantages of using organoids to study pathogenesis?
-less ethical issues
-simpler, cheaper, easier to scale, more variable
-demonstrate multiple cell types and 3D architecture
What are the disadvantages of using organoids to study pathogenesis?
-only mimics aspects of disease
-immortalised cell lines different to original tissue
-specialised growth conditions affect bact behaviour