1. Meningitis and Phase Variation
First discuss that phase variation occurs in Neisseria and go on to explain…

2. Recap: genes and proteins
DNA C T C T G A A T G C U C U G A A U G
RNA
DNA is read in sets of 3 bases (codons) which make up genes. These genes are transcribed into RNA which is then translated into amino acids which make up functional proteins.
Proteins

3. Recap: immunity
Molecules on the surface of bacteria are called antigens
B cells
The immune system recognises antigens on the surface of bacteria which stimulates the production of antibodies specific to that protein. These antibodies then coat the bacteria, targeting it for killing by the immune system.

4. Recap: immunity
Molecules on the surface of bacteria are called antigens
Cells of the immune system recognise antigens and produce antibodies
Antibodies bind to the bacteria’s antigen and kill them
B cells
The immune system recognises antigens on the surface of bacteria which stimulates the production of antibodies specific to that protein. These antibodies then coat the bacteria, targeting it for killing by the immune system.

5. What is Meningitis
Infection of the membranes around the brain and spinal cord
Main cause is a bacteria called Neisseria meningitidis
Meningitis is primarily caused by a bacteria called Neisseria meningitidis. This bacteria causes meningitis when it infects the otherwise sterile membranes around the brain and spinal cord.

6. What are the symptoms?
Fever
Headache
Neck stiffness

7. Neisseria meningitidis
Found in the throats of healthy people.
Only causes disease in rare cases.
Neisseria meningitis is a gram negative pathogen. It colonises the throats of healthy people asymptomatically but in sever cases can infect the meninges and cause meningitis.
N. meningitidis has adapted ways to evade the immune system, which is where phase variation ties in.
Must have a way for its antigens to go unnoticed until it causes disease
Microscope image of N.meningitidis

8. Phase variation = switching genes ON or OFF.
Caused by reversible mutation
Off On
Phase variation is the switching on and off of genes in response to mutation. The mechanism for this will be explained later.
These mutations are reversible, meaning genes can be switched on and off interchangeably.
Mutation

9. What does phase variation look like?
One cell will divide into two daughter cells
With every division, there is a chance they will mutate (mutation rate)
Every time a cell divides there is a random chance they will mutate and switch on/off phase variable genes.
These mutations are then passed down to daughter cells
This mutation will be passed down to the daughter cells
Mutation is random.
Like rolling a dice

10. What does phase variation look like?
It is a reversible process
This process is reversible, whereby mutation can also switch genes back on again.

11. What does phase variation look like?
Many bacteria have more than one phase variable gene
Both genes can mutate at the same time
Many bacteria have multiple phase variable genes that can be switched on/off in tandem giving a wide variety of phenotypes
Mutation isn’t this quick in real bacteria.

12. How does this make the population look?
All of the different cells have the same DNA but have different antigens expressed.
The combination of different phase variable genes can give a population that has arisen from a single cell, which has different proteins expressed on their surface.

13. How does phase variation happen? -Slippery DNA
Poly G tract
THE
CAT
AND
THE
DOG ON
6 G’s
GGG GGG AGC CGA CCG
Reversible
Deletion
One mechanism of phase variation is through slippery or hypermutatable DNA.
Hyper mutatable DNA is far more likely to get insertion/deletion mutations than other sections of DNA
Repeat nucleotide tracts (eg. Poly G above) are hypermutatable
Insertions/ deletions can cause frame shifts which truncate the expressed proteins and put them in the off position.
Insertions deletions can just as easily restore the frame and switch gene expression back on.
STOP
THE
ATA
NDT
HED
OG -
OFF
5 G’s
GGG GGA GCC GAC CG -

14. How can phase variation benefit bacteria?

15. How can phase variation benefit bacteria?
Switching some genes off can help the bacteria to escape the immune system.

16. What genes can be phase variable?
There are lots of different genes that can be phase variable
Some examples in N. meningitidis are genes involved in:
Taking up nutrients such as iron
Sticking to the host cells
Many of these genes are involved in causing disease