Phase variation in Neisseria meningitidis Recap genes and

Phase variation in Neisseria meningitidis

Recap: genes and proteins 1 codon = 1 amino acid G A C T C T G A C U G A T A C A T G A U G DNA RNA Proteins

Recap: immunity Molecules on the surface of bacteria are called antigens B cells

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

What is Meningitis? Infection of the membranes around the brain and spinal cord Neisseria meningitidis is the major cause of bacteria meningitis world wide

Neisseria meningitidis Found in the throats of healthy people. Only causes disease in rare cases. N. meningitidis has several key virulence determinants Microscope image of N. meningitidis

Virulence determinants of N. meningitidis Opa Is an adhesion molecule that allows N. meningitidis to stick to human epithelial cells. Hpu. A Hmb. R Are both haemoglobin receptors responsible for acquiring iron. What do they have in common? All are subject to a process known as phase variation!

Phase variation = switching genes ON or OFF. Caused by reversible mutation Off On 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) Mutation is random. Like rolling a dice This mutation will be passed down to the daughter cells

What does phase variation look like? It is a reversible process

What does phase variation look like? Many bacteria have more than one phase variable gene Both genes can mutate at the same time Mutation isn’t this quick in real bacteria.

What is the effect of phase variation on populations of cells? All of the different cells have the same DNA but have different antigens expressed.

How does phase variation happen? -Slippery DNA

How can phase variation benefit bacteria?

How can phase variation benefit bacteria? Phase varying surface protein expression can help bacteria to evade immune effectors.

Phase variation is a key factor in bacteria’s ability to cause disease

Summary Phase variation is the reversible switching on or off of gene expression Phase variation is caused by mutations in hyper-mutatable DNA sequences Bacteria have many phase variable genes that contribute to their ability to cause disease

Simulating phase variation The attached simulator and work sheets will help you to visualise phase variation in real time. This will also help you to consider the roles of phase variation in disease.