Phase variation in
Neisseria meningitidis
Recap: genes and proteins
1 codon = 1 amino acid
G A G A C T
C T C T G A
C U 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 stick to human epithelial cells.
 HpuA
 HmbR
 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?
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.