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

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

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.

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.

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.

What are the symptoms? Fever Headache Neck stiffness

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

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

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

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

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.

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.

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 -

How can phase variation benefit bacteria?

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

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