Lecture 1 Flashcards
Give a simple definition of a pathogen
An organism capable of causing disease
Define disease
The clinical signs and symptoms of damage that occur in a host as a result of its interaction with an infectious agent
What are the six stages of infection of pathogens and what do these involve?
- Transmission (vector, environment, host restricted)
- Infection (how to enter and breach host barriers)
- Establishment (colonise, survive and spread)
- Persist (Evade the immune system)
- Disease (damage host cells, tissues)
- Antibiotic resistance
What is the importance of bacteria as a area of research?
The rising threat of bacterial antibiotic resistance, creating a global drive in bacterial research. As infections could occur after routine surgery and become fatal.
How does the status of a host affect the progression of disease?
- The immune status of the host
- Whether they have had prior exposure
- Whether they have a genetic predisposition
- immune status (age, stress, diet, surpressed)
What is the progression of disease largely dependent on?
Pathogen/host interations
What features of the pathogen interact with that of the host to determine disease progression?
- Site of infection (related to the pathogen’s properties)
- Specific traits of the bacterial isolate (virulence factors, metabolism, growth characteristics)
- Route of inoculum (tissue specificity of pathogen, host defences)
- Size of inoculum (LD50 = lethal dose 50, the dosage that causes 50% mortality in the animal model.)
What was the inportance of Koch in bacterial studies?
Koch linked pathogens to disease as the causative agents. He proved that specific microorganisms caused a specific disease
What are the purpose of Koch’s postulates?
1890 To prove that a specific microorganism causes a specific disease
What is the one-microbe one-disease concept?
the idea that one microbe should be linked to one disease directly. “it is essential that following isolation of a pure culture of the suspected pathogen, a laboratory culture of the organism should both initiate the disease and be recovered from the animal.”
What are Koch’s 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 cultures microorganism should cause disease when introduced into a healthy organism
- The microorganism must be re-isolated from the inoculated, diseased experimental host and identified as identical to the original specific causative agent
By what process would Koch demonstrate experimentally that a specific microbe causes a specific disease?
- Take a diseased animal and take a smaple of its blood
- Culture the suspected pathogen in pure culture
- Input into a healthy organism and observe disease
- Take blood samples from the experimental host and culture the pathogen
- Confirm that is the same as the original specific causative agent
- Must take samples from healthy individual and not see suspected pathogen
What are the limitations of Koch’s postulates?
They make implicit assumptions that may not translate to reality:
- The pathogen is lab culturable
- The right conditions are known and being used The bacteria may require certain nurtients (fastidious), may have certain O2 requirements or may be unculturable
Give an example of an unculturable pathogen
Catscratch disease In 1990 the pathogen was visualised at large densities around the infected area but culturing failed so the identigy of the pathogen was unknown Bartonella species take 45 days to grow if they do at all as they are fastidious. Involved in emerging diseases, very comnplex and there are many species: 16s rRNA sequencing used to confirm involvment
How have technological advances overcome the limitations of Koch’s postulates for unculturable pathogens?
- The application of 16s rRNA to determine the presence and sequence of the pathogen
- Took four patients with symptoms and visible clusters of bacteria (upon staining) in the affected tissues
- The DNA was extracted from frozen or paraffin embedded tissue
- Using 16s rRNA “universal” eubacterial primers DNA amplified by PCR DNA was cloned and sequenced
- More specific primers were designed and more patients tested, alongside healthy individuals
What are three strategies of baterial pathogenesis?
- Extracellular pathogen
- invasive
- can spread
- e.g. Streptococcus pneumoniae
- Toxin producing pathogens (extracellular)
- e.g. Clostridium botulinum, Vibrio chloera, Escherichia coli O157::H7
- Intracellular pathogen (non-obligate)
- e.g. Salmonella (enterica) serovar Typhimurium, Listeria monocytogenes, Chlamydia spp.
Give examples of virulence factors
- Adhesins (fimbriae, pili, outer membrane proteins)
- Flagella (motility, penetrate mucin)
- Proteins to help obtain rain/essential nutrients (siderophores-iron)
- Toxins
- Capsule
- Immune modulatory proteins
- Type III secretion system
What are the functions of virulence factors?
- Attachment and entry into the body
- Local or general spread in the body
- Multiplication
- Evasion of host defences
- Shedding from the body
- Causing damage in the host
When was the first virulence factor cloned?
1984 A single gene conferring virulence traits on a non-pathogenic E.coli
Define and describe an endotoxin
- lipopolysaccharide of gram negative bacteria
- cell bound
- heat stable
- weakly toxic
- detected by TLR4
What are the general symptoms of an endotoxin?
Fever, diarrhea, vomiting
What is TRL4?
(toll-like receptor) A protein in humans that detects lipopolysaccharides from gram-negative bacteria in order to activate the innate immune system
Define and describe an exotoxin
Proteins released extracellulary produced by certain gram negative and gram positive species
- generally heat liable
- has specific targets
- usually highly toxic
Define and describe an enterotoxin
group of exotoxins that act on the small intestine causing change in the interesting permeability leading to diarrhea
Give three examples of enterotoxins
C.difficile toxin Cholera toxin E.coli toxin