Principles of Pathogenesis

Question 1

Types of Microbes

Answer 1

Very few microbes are always pathogenic – these are called obligates – they don’t live within us or on us in a harmonious way. If they are present, they cause a disease.

Other bacteria live with us that are potentially pathogenic. Normally they don’t cause disease, but if an opportunity presents itself like a wound, they have the opportunity to cause disease
e.g. streptococcus or staphylococcus

Commensals – not pathogenic to humans and provide benefit. evolved and adapted well to living in the colon, do not cause disease, even provide benefit ‘mutualism’ so both benefit. There are as many bacteria in the human as body cells.

Question 2

Sucessful pathogen

Answer 2

Infect a host
May involve binding to surfaces, entry into wound etc, often specific adhesins important

Be able to replicate and survive
Derive nutrition, avoid the host response

Transmit to new hosts
Be expelled into the environment or transferred to another host

Question 3

What each virulence factor does from a pathogen?

Answer 3

Delete gene, show loss of virulence in model system, add gene back (e.g. on plasmid), show restoration of virulence

Distinguishes pathogen from commensal- Comparative genomics

Expressed or essential in vivo.
Certain virulence factors are evident in vivo, but once taken out into the lab, certain functions are lost.

Question 4

Steps in successful infection

Answer 4

1.Swim
Motility is crucial for virulence in some cases
H pylori is motile – swimming is imp for GIT pathogens for attachment to epitelaial cells and bacteria need to swim through that mucus to get to the cells

2.Sense environment
Bacteria need to sense their environment and generate a response according to that.
Quorum sensing relies on making bacteria sense if they are alone or within colonies.
Only within one species. And to communicate between them. Once concentration reaches theresshold it will tell community that they are in a colony

3.Switch virulence factors on and off
A multi-layered hierarchy
Producing virulence factors, switching those genes on costs bacteria a lot of energy, so they have to be able to switch them on and off.
1. DNA level – by changing the DNA sequence –
2. Gene regulation – by activating and suppressing genes
3. Post translational regulation – deactivating proteins after they have been made

4.Stick
Sticking to prevent washing the bacteria away.
They need to be extracellular attachments. G+ and G- vary in their attachments. They have adhesins, and fimbrii (small projections) that mediate attachments
G- have other adhesins.
There are different types of adhesins for different types of environments.

5.Stealth avoid the immune system
Bacteria can degrade antibodies
They can resist complement (using capsules and membrane proteins to resist complement so they are not recognized
They hide by coating themselves with something that makes them look like normal host cell so not recognised as foreign

6.Subvert (sabotage or overturn)
Manipulation of host
Using host’s own mechanisms for its own purpose
Use our cell’s machinery/systems for their own benefit.

7.Spread
Infection can require translocation through the body and often pathogens will have a tropism for particular organ(s)

8.Scatter
Transmit to new host to establish new infection
Zoonosis (crossing species)