Lecture 1 Flashcards
(42 cards)
What is a Disease?
Clinical signs and symptoms of damage that occur in a host as a result of its interaction with an infectious agent
What factors effect a host’s likelihood of infection?
Immune status (age, stress, diet and previous illness)
Prior Exposure
Genetic Predisposition
What effects a bacteria’s ability to initiate infection?
Site of initial infection
Specific traits of bacterial isolate (virulence factors, metabolism, growth characteristics)
Route of Inoculum
Size of inoculum
What does LD50 stand for?
Lethal dose 50 of inoculum: dosage that causes 50% mortality in animal model
What was the aim of Koch’s Postulates?
Proving that a specific microorganism causes a specific disease
What are Koch’s four postulates?
1) The microorganism must be found in abundance in all organisms suffering from the disease, but should not be found in healthy organisms
2) The microorganism must be isolated from diseased organism and grown in pure culture
3) The cultures organism should cause disease when introduced into a healthy organism
4) The microorganism must be re-isolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent.
What are the implicit assumptions of Koch’s postulates?
1) The pathogen is culturable (in the lab)
2) The right condition are being used
- Nutrients
- O2 levels
Give an example of a disease which could not be cultured in the lab and therefore appeared to go against Koch’s postulates
And describe how the microorganism was eventually found
Cat Scratch Disease: Required 45 days to Culture
Discovered using 16S rRNA
-DNA extracted from tissue shown to have visble clusters when stained
-DNA was amplified using 16S rRNA eubacterial primer for PCR
-The DNA was cloned and sequenced
What are the three main types of bacterial pathogens?
Extracellular Invasive Pathogens
Extracellular Toxin Producing Pathogens
Intracellular Pathogens (non-obligates)
In order the establish and infection and cause disease pathogens must have strategies to facilitate what 6 processes?
1) Attachment and entry in the body
2) Local or general spread in the body
3) Multiplication
4) Evasion of host defences
5) Shedding from body
6) Causing damage to the host
What is used to facilitate all of those processes?
Virulence Factors
Give seven examples of virulence factors
Adhesins Flagella Proteins to help obtain rare/essential nutrients Toxins Capsule Immune Modulatory Proteins Type III Secretory System
What was the first virulence factor cloned? What was it’s use?
Invasin - cloned in 1984, from Yersis pseudotuberculosis
Gave ability to avoid immune system
-Highlighted by conferring ability onto non-pathogenic Escherichia coli
What is an Endotoxin?
A lipopolysaccharide from Gram -ve bacteria Cell bound Heat Stable Causes fever, diarrhoea and vomiting Weakly toxic
What is an exotoxin?
Protein Released extracellulary by certain Gram +ve and -ve bacteria
Heat Labile
Highly toxic
Very Specific
What is an enterotoxin?
Give examples
Group of exotoxins that act specifically on the small intestine , causing changes in intestinal permeability leading to diarrhoea e.g. Clodtridium difficile toxin A, cholera toxin and Escherichia coli toxins
What do you call a toxin inactivated for use as a vaccine?
Toxoid
Name a bacterium species which produces the most potent neurotoxin
Describe its action and how it is now used in clinical settings
Clostridium botulinum - a Gram +ve, anaerobic spore former
(1ng can kill 1 million guinea pigs)
Blocks acetylcholine release in synapses causing flaccid paralysis and respiratory arrest
Used for relief of spasticity, chronic migraine, excessive sweating, overactive bladder and botox
How was Invasin confirmed as a single gene?
Large Y. tuberculosis genome fragments cloned in E.coli, clones enriched to allow E.coli to invade host cells, gene pinpointed using transposon mutagenesis; loss of invasion capability due to loss of single gene
What three additional postulates were added for Molecular Koch’s postulates?
1) Phenotype associated with pathogenic strains of species
2) Inactivation of gene should lead to measurable reduction in virulence or if the is gene isolated will be able to confer trait
3) Replacing mutant gene with wild type should restore virulence
What bacteria releases the cholera toxin?
How is it transmitted?
Where does it colonize?
What effect does it have?
What additional virulence factors does this bacterium employ?
Vibrio cholerae Water-oral Small intestine The exotoxin causes increased adenylate cyclase activity; increasing cAMP levels and effects sodium/chloride flux in/out of cell (see Microbiology module for more). This leads to loss of fluid and electrolytes (aka diarrhoea) Adhesin, Mucinase, Flagella
Where did the cholera toxin come from?
Part of genome of lysogenic phage
What is TCP?
What is its role?
Toxin co-regulated pilus
Required for colonization and acts as receptor for other phage
What is a pathogen?
An organism capable of causing disease
