Most bacteria alternate between a multicellular slime city stage, in which they form a slimy film over solid
surfaces in soil or water, and a dispersal stage in which cells float or swim or glide away from the slime city
in order to find new suitable habitats. Bacterial cells may continue to multiply in both stages (most bacteria
multiply by binary fission - a cell grows and splits into two new cells, each of which grows and splits again,
and so on) and they always maintain a certain individuality. In fact for many decades microbiologists
thought that only the minority of bacterial species possessed a multicellular slime stage, but now the
majority appear to do so. This is because the slime is easily disrupted - the cells are only held together by
sticky slime, and are often not in direct physical contact with one another. This is quite different from cells
in the human body, in which the cells are physically strongly connected to one another. Even so, in your
body certain types of cells are free to wander as 'individuals' such as your white blood cells and
macrophages which wander around the body collecting garbage and fighting foreign cells that enter the
body, such as bacterial invaders. However, even when physically separated and swimming around in
different directions, bacteria can still function to some extent as a single individual, because they
communicate with one another. There is thus still a tendency to use the word 'cell' interchangeably with
bacterium, as if bacteria really are single celled organisms.
In the diagram above, two bacteria are swimming in water - these may be motile cells leaving a slime city to
find new surfaces to colonise. Bacterium A is releasing a signal which has been received or detected by
bacterium B. First let us consider the signal - what type of signal is it, is it light, sound, or something else?
Bacteria communicate principally by using chemical signals - the signal is a chemical released into the
surrounding water. Various chemicals may be used, including small peptides (small proteins). The
molecules (particles) of this chemical can be transported in two ways - they may be carried large distances
by bulk movement of the water, such as by eddies and currents, or they may diffuse across short
distances.
What is diffusion:
Small particles released into air or water move about since they possess thermal energy (thermal energy is
really the energy of motion of the particles, in hot air molecules of oxygen move about faster than they do
in cold air). However, particles frequently collide with the molecules of their medium (air or water) or with
one another. This causes them to undertake a kind of random motion - in which they get jostled about and
so change direction frequently as they collide with other particles. This produces a random walk, an
example of which is shown below for a particle starting where the circle is and ending where the arrowhead
is. Each place where the particle has changed direction is where it has collided with another particle, for
example this could be a microscopic particle of smoke diffusing into still air and colliding with air molecules.
surfaces in soil or water, and a dispersal stage in which cells float or swim or glide away from the slime city
in order to find new suitable habitats. Bacterial cells may continue to multiply in both stages (most bacteria
multiply by binary fission - a cell grows and splits into two new cells, each of which grows and splits again,
and so on) and they always maintain a certain individuality. In fact for many decades microbiologists
thought that only the minority of bacterial species possessed a multicellular slime stage, but now the
majority appear to do so. This is because the slime is easily disrupted - the cells are only held together by
sticky slime, and are often not in direct physical contact with one another. This is quite different from cells
in the human body, in which the cells are physically strongly connected to one another. Even so, in your
body certain types of cells are free to wander as 'individuals' such as your white blood cells and
macrophages which wander around the body collecting garbage and fighting foreign cells that enter the
body, such as bacterial invaders. However, even when physically separated and swimming around in
different directions, bacteria can still function to some extent as a single individual, because they
communicate with one another. There is thus still a tendency to use the word 'cell' interchangeably with
bacterium, as if bacteria really are single celled organisms.
In the diagram above, two bacteria are swimming in water - these may be motile cells leaving a slime city to
find new surfaces to colonise. Bacterium A is releasing a signal which has been received or detected by
bacterium B. First let us consider the signal - what type of signal is it, is it light, sound, or something else?
Bacteria communicate principally by using chemical signals - the signal is a chemical released into the
surrounding water. Various chemicals may be used, including small peptides (small proteins). The
molecules (particles) of this chemical can be transported in two ways - they may be carried large distances
by bulk movement of the water, such as by eddies and currents, or they may diffuse across short
distances.
What is diffusion:
Small particles released into air or water move about since they possess thermal energy (thermal energy is
really the energy of motion of the particles, in hot air molecules of oxygen move about faster than they do
in cold air). However, particles frequently collide with the molecules of their medium (air or water) or with
one another. This causes them to undertake a kind of random motion - in which they get jostled about and
so change direction frequently as they collide with other particles. This produces a random walk, an
example of which is shown below for a particle starting where the circle is and ending where the arrowhead
is. Each place where the particle has changed direction is where it has collided with another particle, for
example this could be a microscopic particle of smoke diffusing into still air and colliding with air molecules.
| Bacterial Communication Systems |
Note that although the particle is moving at random, it has moved a certain amount overall, toward the
right. Diffusion is very rapid over small distances (of up to one millimetre or so) but it would take a long
time for a particle to diffuse from one end of a room to the other, since sometimes the particle will move
back in the direction from whence it came. When someone breaks open a stink bomb capsule at one end
of a room, the hydrogen sulphide molecules released diffuse outwards and if the air is very still, it may take
a long time for the odour to reach the far end of the room. However, currents of air caused by a breeze
through an open window or by people waving their arms about will mix the air and transport the odour more
rapidly (by the mass movement of the air, a process called advection). Either way, the odour slowly
spreads out to fill the room, but for a long time the smell will be strongest near to the source (the stink
bomb).
Bacterial chemical signals work in exactly the same way - signalling molecules diffuse or get advected from
the source (the cell emitting the signal) and so spread out in all directions. We can draw imaginary spheres
around the signal emitting cell, showing the signal as it radiates outwards. The further one is from the cell,
the longer it takes the signal to arrive and also the weaker the signal will be, since it takes more molecules
to fill a larger sphere than a smaller one. Thus, the further we are from the cell, the lower the concentration
of signally molecules (the concentration is the number of signal molecules per cubic centimetre of water)
and so the weaker the signal becomes, since signal strength is proportional to signal molecule
concentration. This creates a concentration gradient of signalling molecules around the source cell, as
shown below:
right. Diffusion is very rapid over small distances (of up to one millimetre or so) but it would take a long
time for a particle to diffuse from one end of a room to the other, since sometimes the particle will move
back in the direction from whence it came. When someone breaks open a stink bomb capsule at one end
of a room, the hydrogen sulphide molecules released diffuse outwards and if the air is very still, it may take
a long time for the odour to reach the far end of the room. However, currents of air caused by a breeze
through an open window or by people waving their arms about will mix the air and transport the odour more
rapidly (by the mass movement of the air, a process called advection). Either way, the odour slowly
spreads out to fill the room, but for a long time the smell will be strongest near to the source (the stink
bomb).
Bacterial chemical signals work in exactly the same way - signalling molecules diffuse or get advected from
the source (the cell emitting the signal) and so spread out in all directions. We can draw imaginary spheres
around the signal emitting cell, showing the signal as it radiates outwards. The further one is from the cell,
the longer it takes the signal to arrive and also the weaker the signal will be, since it takes more molecules
to fill a larger sphere than a smaller one. Thus, the further we are from the cell, the lower the concentration
of signally molecules (the concentration is the number of signal molecules per cubic centimetre of water)
and so the weaker the signal becomes, since signal strength is proportional to signal molecule
concentration. This creates a concentration gradient of signalling molecules around the source cell, as
shown below:
The red circles represent the signal and the further apart they are, the weaker the signal, this is called a
concentration gardient as it's rather like a hill on a map - the steeper the hill, the closer together the
contours on a map will be. (Likewise the further apart the arrows are, the weaker the signal as the
molecules are spread over a larger area). It is signal gradients such as these that allow white blood cells
(part of your immune system) to sniff out bacteria that enter your body - the white cell will measure the
signal gradient and move 'uphill' that is it will move in the direction of increasing signal strength until it
locates the bacterium, and then it will attempt to destroy it. This is not what the bacterium intends however!
It intends to use these signals to its advantage by using it to 'talk' to its fellows.
For the system to work the bacteria need to be able to detect the signals. There are various ways of doing
this, but basically the signal molecule has to bind (stick) to a receptor molecule, which is often on the cell
surface but maybe inside the cell. This receptor will only stick to those signal molecules it is 'designed' to
detect. This is rather like a lock-and-key mechanism - the key is the signal and the lock is the receptor.
Only the right key can bind to the receptor and activate it. Once the receptor molecule is activated in this
way, it amplifies the signal and alerts the whole cell that a signal has been detected. Let us look at some
specific examples.
Quorum sensing
Bacteria may release signal molecules called autoinducers - because they induce a response in the same
type of bacterium that is emitting a signal, so a cell of the bacterium Pseudomonas aeruginosa will
communicate with other cells of Pseudomonas aeruginosa and the signal will induce a response in these
cells. This process is called quorum sensing as the bacteria sense the presence of their own kind nearby.
This allows them to monitor the density of their population - that is to tell how many of its own kind are
nearby. This is an example of cell to cell communication in bacteria. Bacteria can also listen into the
communications of other species if they are able to decode their signals (to sense and decode the signals
they need the correct receptor).
First of all, each cell has to produce and release a signal that its own kind will recognise - the autoinducer
molecules. These molecules then diffuse out and are detected by bacteria with the correct receptor to
detect and decode the signal. The cell receiving the signal then responds in some way.
The diagram below shows this process in a cell of the bacterium Vibrio fischeri, which lives in the sea and
inside certain animals in the sea.
concentration gardient as it's rather like a hill on a map - the steeper the hill, the closer together the
contours on a map will be. (Likewise the further apart the arrows are, the weaker the signal as the
molecules are spread over a larger area). It is signal gradients such as these that allow white blood cells
(part of your immune system) to sniff out bacteria that enter your body - the white cell will measure the
signal gradient and move 'uphill' that is it will move in the direction of increasing signal strength until it
locates the bacterium, and then it will attempt to destroy it. This is not what the bacterium intends however!
It intends to use these signals to its advantage by using it to 'talk' to its fellows.
For the system to work the bacteria need to be able to detect the signals. There are various ways of doing
this, but basically the signal molecule has to bind (stick) to a receptor molecule, which is often on the cell
surface but maybe inside the cell. This receptor will only stick to those signal molecules it is 'designed' to
detect. This is rather like a lock-and-key mechanism - the key is the signal and the lock is the receptor.
Only the right key can bind to the receptor and activate it. Once the receptor molecule is activated in this
way, it amplifies the signal and alerts the whole cell that a signal has been detected. Let us look at some
specific examples.
Quorum sensing
Bacteria may release signal molecules called autoinducers - because they induce a response in the same
type of bacterium that is emitting a signal, so a cell of the bacterium Pseudomonas aeruginosa will
communicate with other cells of Pseudomonas aeruginosa and the signal will induce a response in these
cells. This process is called quorum sensing as the bacteria sense the presence of their own kind nearby.
This allows them to monitor the density of their population - that is to tell how many of its own kind are
nearby. This is an example of cell to cell communication in bacteria. Bacteria can also listen into the
communications of other species if they are able to decode their signals (to sense and decode the signals
they need the correct receptor).
First of all, each cell has to produce and release a signal that its own kind will recognise - the autoinducer
molecules. These molecules then diffuse out and are detected by bacteria with the correct receptor to
detect and decode the signal. The cell receiving the signal then responds in some way.
The diagram below shows this process in a cell of the bacterium Vibrio fischeri, which lives in the sea and
inside certain animals in the sea.
How do we interpret such a 'circuit' diagram?
First of all, notice that we have cut a piece out of the cell at the bottom and enlarged it. The four curved
purple lines represent the various layers of the cell envelope (the cell 'skin'). Since this bacterium is of the
Gram negative type, it has two membranes, the outer membrane (OM) and the inner membrane (IM) and
each membrane is a double layer of phospholipids and so is drawn as a double line. The region outside
the cell (the surrounding water) is shown at the top, and the region inside the cell (the cytoplasm) is shown
underneath the cell envelope. The arrows indicate the flow of signals.
Notice that the cell releases (or secretes) a substance called AHL to the outside - this is the signal
molecule (a chemical called acyl-homoserine lactone or AHL). The same cell can also detect a AHL signal,
since AHL is able to freely cross the membranes and so can diffuse in or out, and so on the right a
molecule of AHL is shown entering the cell. This molecule could be one that the cell secreted or it could be
from a neighbouring cell. (It does not matter, what matters is the total strength of the signal which will only
be very high when lots of signal emitting cells are close together).
The AHL enters the cell and binds to its receptor, which is a protein called LuxR. LuxR (the lock) will
specifically bind to AHL (the key). Only when AHL is bound to LuxR will it then bind to a specific region of
DNA called the luxICDABE (or luciferase) operon.
What is an operon:
An operon is a series of genes operated by a single common switch. LuxR-AHL (LuxR with AHL bound)
activates this switch when it binds to it. Once the switch is on, the genes on the operon, in this case
luxICDABE will become active. This is a group of genes: luxI, luxC, luxD, luxA, luxB and luxE. A gene can be
defined as a region of DNA that contains the instructions to make a specific protein. In this case, the
proteins are: LuxI, LuxC, luxD, luxA, luxB and LuxE. Note that proteins are written with an initial capital and
genes are italicised, to avoid confusion: e.g. the luxA gene contains the instructions needed to make the
LuxA protein.
Thus, when AHL enters the cell, it binds to LuxR which then switches on the genes luxICDABE, causing
more of the proteins LuxI, LuxC, luxD, luxA, luxB and LuxE to be synthesised within the cell. These proteins
then produce a response in the cell. LuxI is an enzyme that synthesises AHL, so one response is that the
cell puts out a stronger signal (this is called positive feedback - the circuit amplifies itself). The other Lux
proteins create the enzyme luciferase, so called because it produces light! (Lux is Latin for light, hence the
name of the Lux proteins).
So, when a Vibrio fischeri bacterium senses the presence of other bacteria of its own kind, it produces
more light. In this way, a single bacterial cell does not waste energy producing light (its own signal is too
weak), since each cell is microscopic its light could not be seen and so this would be a waste of energy.
Instead Vibrio fischeri only emit light when they are present in large numbers. Why is this useful?
Many fish contain Vibrio fischeri and use the bacteria to produce light for various purposes, including to
help the fish see in the dark, or for defence by dazzling attackers or for communication with other fish, and
supply the bacteria with nutrients and a safe home for their services. Also, it is thought that when a fish
containing these bacteria dies and sinks to the dark ocean floor, the bacteria start to feed off its carcass
and multiply as they do so. Eventually they reach large numbers, and they sense this by detecting their
neighbours through quorum sensing - the more cells that are present, the stronger the signal and the
more light produced. Now other fish can easily see the carcass glowing in the dark and swim over to eat it,
ingesting the bacteria as they do so. The bacteria then colonise the new fish and when this fish dies, the
bacteria will break out and eat its corpse, and glow in the dark, and the cycle repeats.
Production of light by living organisms is called bioluminescence and is a very common phenomenon. The
light produced is a cold light - only 5% of the energy is released as heat, compared to 90% for a normal
light bulb - bioluminescence is ten times more efficient than a household light bulb!
Quorum sensing in Gram positive bacteria
Let us look at a second example of quorum sensing, this time in the bacterium Staphylococcus aureus.
This bacterium lives on the skin and in the nose of humans, but can sometimes cause minor diseases,
such as pimples, boils and abscesses or life-threatening diseases such as pneumonia, septicaemia and
meningitis. It is a type of bacterium called Gram positive, which means that its envelope has only one
membrane and not two (so we represent it as one pair of purple lines). These bacteria release a signalling
molecule called autoinducing peptide (AIP) (a peptide is essentially a small protein).
First of all, notice that we have cut a piece out of the cell at the bottom and enlarged it. The four curved
purple lines represent the various layers of the cell envelope (the cell 'skin'). Since this bacterium is of the
Gram negative type, it has two membranes, the outer membrane (OM) and the inner membrane (IM) and
each membrane is a double layer of phospholipids and so is drawn as a double line. The region outside
the cell (the surrounding water) is shown at the top, and the region inside the cell (the cytoplasm) is shown
underneath the cell envelope. The arrows indicate the flow of signals.
Notice that the cell releases (or secretes) a substance called AHL to the outside - this is the signal
molecule (a chemical called acyl-homoserine lactone or AHL). The same cell can also detect a AHL signal,
since AHL is able to freely cross the membranes and so can diffuse in or out, and so on the right a
molecule of AHL is shown entering the cell. This molecule could be one that the cell secreted or it could be
from a neighbouring cell. (It does not matter, what matters is the total strength of the signal which will only
be very high when lots of signal emitting cells are close together).
The AHL enters the cell and binds to its receptor, which is a protein called LuxR. LuxR (the lock) will
specifically bind to AHL (the key). Only when AHL is bound to LuxR will it then bind to a specific region of
DNA called the luxICDABE (or luciferase) operon.
What is an operon:
An operon is a series of genes operated by a single common switch. LuxR-AHL (LuxR with AHL bound)
activates this switch when it binds to it. Once the switch is on, the genes on the operon, in this case
luxICDABE will become active. This is a group of genes: luxI, luxC, luxD, luxA, luxB and luxE. A gene can be
defined as a region of DNA that contains the instructions to make a specific protein. In this case, the
proteins are: LuxI, LuxC, luxD, luxA, luxB and LuxE. Note that proteins are written with an initial capital and
genes are italicised, to avoid confusion: e.g. the luxA gene contains the instructions needed to make the
LuxA protein.
Thus, when AHL enters the cell, it binds to LuxR which then switches on the genes luxICDABE, causing
more of the proteins LuxI, LuxC, luxD, luxA, luxB and LuxE to be synthesised within the cell. These proteins
then produce a response in the cell. LuxI is an enzyme that synthesises AHL, so one response is that the
cell puts out a stronger signal (this is called positive feedback - the circuit amplifies itself). The other Lux
proteins create the enzyme luciferase, so called because it produces light! (Lux is Latin for light, hence the
name of the Lux proteins).
So, when a Vibrio fischeri bacterium senses the presence of other bacteria of its own kind, it produces
more light. In this way, a single bacterial cell does not waste energy producing light (its own signal is too
weak), since each cell is microscopic its light could not be seen and so this would be a waste of energy.
Instead Vibrio fischeri only emit light when they are present in large numbers. Why is this useful?
Many fish contain Vibrio fischeri and use the bacteria to produce light for various purposes, including to
help the fish see in the dark, or for defence by dazzling attackers or for communication with other fish, and
supply the bacteria with nutrients and a safe home for their services. Also, it is thought that when a fish
containing these bacteria dies and sinks to the dark ocean floor, the bacteria start to feed off its carcass
and multiply as they do so. Eventually they reach large numbers, and they sense this by detecting their
neighbours through quorum sensing - the more cells that are present, the stronger the signal and the
more light produced. Now other fish can easily see the carcass glowing in the dark and swim over to eat it,
ingesting the bacteria as they do so. The bacteria then colonise the new fish and when this fish dies, the
bacteria will break out and eat its corpse, and glow in the dark, and the cycle repeats.
Production of light by living organisms is called bioluminescence and is a very common phenomenon. The
light produced is a cold light - only 5% of the energy is released as heat, compared to 90% for a normal
light bulb - bioluminescence is ten times more efficient than a household light bulb!
Quorum sensing in Gram positive bacteria
Let us look at a second example of quorum sensing, this time in the bacterium Staphylococcus aureus.
This bacterium lives on the skin and in the nose of humans, but can sometimes cause minor diseases,
such as pimples, boils and abscesses or life-threatening diseases such as pneumonia, septicaemia and
meningitis. It is a type of bacterium called Gram positive, which means that its envelope has only one
membrane and not two (so we represent it as one pair of purple lines). These bacteria release a signalling
molecule called autoinducing peptide (AIP) (a peptide is essentially a small protein).
AIPs cannot freely cross membranes, so they are exported or pumped out of the cell by a protein called
AgrB, shown on the right. To put things into perspective, a typical protein is only one 10 millionths of a
millimetre in diameter - we are looking at very small machinery called nano-machinery. First the protein
AgrD binds to the exporter and has a bit cut off to form AIP which is then exported (AgrD is the AIP
precursor or AIP with a bit of extra peptide attached).
AIP binds to a receptor (the protein AgrC) in the membrane. This receptor then takes a phosphate
molecule (Pi) from the cytoplasm and sticks it to a protein called AgrA to form phosphorylated AgrA or
AgrA~P, AgrA with a phosphate attached). Only when phosphorylated in this way can AgrA bind to the
DNA switch P3-P2 which switches on the synthesis of two sets of genes - one is the agrBDCA sequence of
genes, and the other produces not a protein but a molecule called RNAIII (RNA-three). AgrD protein,
manufactured according to instructions encoded in the acrD gene when the gene is active, is the
precursor which the exporter AgrB uses to make more AIP. This is positive feedback again - AIP has
stimulated its own synthesis and synthesis of its own exporter, so the cell releases a stronger signal.
The RNAIII is a regulator molecule which activates other genes that produce secreted factors and switches
off genes that produce cell adhesion proteins. Note that in these diagrams, an arrow indicates a positive
effect, causing something to increase or to switch on, whilst a line ending in a flat cross-line indicates a
negative response which diminishes something or switches it off. When Staphylococcus aureus is present
in low numbers, its aim is to colonise a surface (such as human tissue inside the body) and so produce a
biofilm. To do this it must synthesise cell adhesion proteins - proteins that act as glue and stick or adhere
the cells to the surface and possibly to each other. However, when its population reaches a high density,
then the cells decide to move on and colonise new surfaces - the AIP signal is strong as their are many
bacteria present, and this increases the levels of RNAIII, causing adhesion proteins to be switched off and
causing the release or secretion of 'factors' including enzymes that destroy human tissue (digest it for
food) and toxins that kill human cells which the bacteria then eat. Understanding quorum-sensing is thus
essential in understanding how bacteria cause disease and why bacteria like Staphylococcus aureus are
harmless inhabitants of the skin one moment, and then become aggressive bacteria that eat the lungs.
Amplifying the signal
If only a single tiny AIP molecule binds to a Staphylococcus aureus bacterium, then that is a very weak
signal that would have little effect. However, the signal detection system has a built in amplifier. When the
AgrC receptor is activated by binding to a molecule of AIP, it phosphorylates a AgrA molecule, however, it
doesn't amplify just one molecule of AgrA, but several, so now we have gone from having one signal
molecule to having several active secondary signalling molecules (AgrA~P) inside the cell - the signal has
been amplified. This is a relatively weak amplifier - we do not want a weak signal to induce a response, that
would defeat the purpose of quorum sensing. Later we shall see signalling systems with very strong
amplifiers, allowing cells to react to a single signalling molecule.
Several quorum circuits operating in parallel
Our third example looks at the bacterium Vibrio harveyi. This bacterium secrete three different
autoinducers: HAI-1 (a type of homoserine lactone), CAI-1 and AI-1. Each type of autoinducer signal binds
to a separate membrane-bound receptor protein (CqsS for CAI-1, LuxN for HAI-1 and LuxQ for AI-1). The
signalling circuits are shown below:
AgrB, shown on the right. To put things into perspective, a typical protein is only one 10 millionths of a
millimetre in diameter - we are looking at very small machinery called nano-machinery. First the protein
AgrD binds to the exporter and has a bit cut off to form AIP which is then exported (AgrD is the AIP
precursor or AIP with a bit of extra peptide attached).
AIP binds to a receptor (the protein AgrC) in the membrane. This receptor then takes a phosphate
molecule (Pi) from the cytoplasm and sticks it to a protein called AgrA to form phosphorylated AgrA or
AgrA~P, AgrA with a phosphate attached). Only when phosphorylated in this way can AgrA bind to the
DNA switch P3-P2 which switches on the synthesis of two sets of genes - one is the agrBDCA sequence of
genes, and the other produces not a protein but a molecule called RNAIII (RNA-three). AgrD protein,
manufactured according to instructions encoded in the acrD gene when the gene is active, is the
precursor which the exporter AgrB uses to make more AIP. This is positive feedback again - AIP has
stimulated its own synthesis and synthesis of its own exporter, so the cell releases a stronger signal.
The RNAIII is a regulator molecule which activates other genes that produce secreted factors and switches
off genes that produce cell adhesion proteins. Note that in these diagrams, an arrow indicates a positive
effect, causing something to increase or to switch on, whilst a line ending in a flat cross-line indicates a
negative response which diminishes something or switches it off. When Staphylococcus aureus is present
in low numbers, its aim is to colonise a surface (such as human tissue inside the body) and so produce a
biofilm. To do this it must synthesise cell adhesion proteins - proteins that act as glue and stick or adhere
the cells to the surface and possibly to each other. However, when its population reaches a high density,
then the cells decide to move on and colonise new surfaces - the AIP signal is strong as their are many
bacteria present, and this increases the levels of RNAIII, causing adhesion proteins to be switched off and
causing the release or secretion of 'factors' including enzymes that destroy human tissue (digest it for
food) and toxins that kill human cells which the bacteria then eat. Understanding quorum-sensing is thus
essential in understanding how bacteria cause disease and why bacteria like Staphylococcus aureus are
harmless inhabitants of the skin one moment, and then become aggressive bacteria that eat the lungs.
Amplifying the signal
If only a single tiny AIP molecule binds to a Staphylococcus aureus bacterium, then that is a very weak
signal that would have little effect. However, the signal detection system has a built in amplifier. When the
AgrC receptor is activated by binding to a molecule of AIP, it phosphorylates a AgrA molecule, however, it
doesn't amplify just one molecule of AgrA, but several, so now we have gone from having one signal
molecule to having several active secondary signalling molecules (AgrA~P) inside the cell - the signal has
been amplified. This is a relatively weak amplifier - we do not want a weak signal to induce a response, that
would defeat the purpose of quorum sensing. Later we shall see signalling systems with very strong
amplifiers, allowing cells to react to a single signalling molecule.
Several quorum circuits operating in parallel
Our third example looks at the bacterium Vibrio harveyi. This bacterium secrete three different
autoinducers: HAI-1 (a type of homoserine lactone), CAI-1 and AI-1. Each type of autoinducer signal binds
to a separate membrane-bound receptor protein (CqsS for CAI-1, LuxN for HAI-1 and LuxQ for AI-1). The
signalling circuits are shown below:
To understand this system requires a bit of knowledge of how DNA works. The information contained
in the molecule of DNA comprises genes. These genes mostly carry information for the synthesis of
proteins, though some are switches for other genes and some encode for the synthesis of RNA
molecules. The message in DNA can be directly transcribed (transcribed literally means that a copy of
the information, or a transcript, is written) into RNA but cannot be directly transcribed into protein.
Thus, DNA always produces RNA first. Many of these RNAs then carry the information copied from the
DNA across to the protein making factories of the cell (these assembly factories are called ribosomes
and each cell has many hundreds of such factories), they act as messengers and so are called
messenger RNAs or mRNAs. The mRNA message can then be translated by the ribosomes, which use
these instructions to assemble the required protein. Proteins are the principle components of the
cell's machinery. Thus, DNA is transcribed into mRNA which moves to the ribosomes where it is
translated and the protein assembled.
All three receptors phosphorylate the same amplifier molecule, the protein LuxU which passes its
phosphate onto a second protein LuxO. However, the receptors only do this when autoinducers are
NOT bound to them - this is their default behaviour. Phosphorylated LuxO, LuxO~P, binds to a
specific region of DNA which codes for the production of five small RNA molecules (sRNAs) which are
transcribed from the DNA. These sRNAs do not act as messengers for the ribosomes, however,
instead they bind to and destabilise and thus cause the destruction of the mRNA for the protein LuxR.
With less messenger RNA, less LuxR is produced. Remember that LuxR is required to make light, so
when no (or very little) autoinducers are present the receptors bring about a drop in LuxR and the
bacterium does not produce light.
When autoinducers do bind to the receptors, they reverse their function and remove phosphate from
LuxU~P, and the LuxU produced removes phosphate from LuxO~P - the arrows are reversed and the
amount of sRNA produced diminishes and the LuxR mRNA is not destroyed, but accumulates and
brings about increased synthesis of LuxR protein which causes light production by activating the
luxCDABE genes, exactly as in the Vibrio fischeri example above (example 1). Thus, we have the
Vibrio fischeri system with added controls.
Why use three autoinducers?
The three signals and three receptors may work as coincidence detectors. It is possible that another
species of bacterium can produce a signal molecule similar enough to CAI-1, for example, to activate
this circuit by accident. By requiring three unique signals or three unique keys, the bacteria can be
sure that they are really listening to signals from their own species - they have an added level of
security to avoid false alarms as all three receptor must be activated simultaneously for a sufficient
response - something which is highly unlikely to occur by chance. Such devices can be important in
the busy world of bacterial communication where signals can get confused (like wires getting crossed)
and where some bacteria will also try to jam or otherwise exploit the signals of others. Since these
three circuits operate together, side by side, we say that they operate in parallel.
Several quorum sensing circuits operating in series
Our fourth example adds a bit more complexity! We look at the Gram negative bacterium
Pseudomonas aeruginosa, which occurs almost everywhere - in water, in soil and can cause disease
in people whose immune systems are weakened. Once again, quorum sensing is essential for this
organism to invade the human body and cause disease.
This bacterium emits two quorum signalling molecules: LasI (similar to LuxI) synthesises a AHL signal
molecule, which I have called AHL-1 and RhlI synthesises another AHL, which I have called AHL-2.
Thus we have two Lux-like circuits. AHL-1 binds to its receptor protein, LasR, whilst AHL-2 binds to the
receptor protein RhlR. RhlR is a DNA regulator (the R on the end of these protein names means
regulator) as it binds to a DNA switch (when bound to AHL-2) causing transcription of the genes
encoded in the Rhl regulon.
in the molecule of DNA comprises genes. These genes mostly carry information for the synthesis of
proteins, though some are switches for other genes and some encode for the synthesis of RNA
molecules. The message in DNA can be directly transcribed (transcribed literally means that a copy of
the information, or a transcript, is written) into RNA but cannot be directly transcribed into protein.
Thus, DNA always produces RNA first. Many of these RNAs then carry the information copied from the
DNA across to the protein making factories of the cell (these assembly factories are called ribosomes
and each cell has many hundreds of such factories), they act as messengers and so are called
messenger RNAs or mRNAs. The mRNA message can then be translated by the ribosomes, which use
these instructions to assemble the required protein. Proteins are the principle components of the
cell's machinery. Thus, DNA is transcribed into mRNA which moves to the ribosomes where it is
translated and the protein assembled.
All three receptors phosphorylate the same amplifier molecule, the protein LuxU which passes its
phosphate onto a second protein LuxO. However, the receptors only do this when autoinducers are
NOT bound to them - this is their default behaviour. Phosphorylated LuxO, LuxO~P, binds to a
specific region of DNA which codes for the production of five small RNA molecules (sRNAs) which are
transcribed from the DNA. These sRNAs do not act as messengers for the ribosomes, however,
instead they bind to and destabilise and thus cause the destruction of the mRNA for the protein LuxR.
With less messenger RNA, less LuxR is produced. Remember that LuxR is required to make light, so
when no (or very little) autoinducers are present the receptors bring about a drop in LuxR and the
bacterium does not produce light.
When autoinducers do bind to the receptors, they reverse their function and remove phosphate from
LuxU~P, and the LuxU produced removes phosphate from LuxO~P - the arrows are reversed and the
amount of sRNA produced diminishes and the LuxR mRNA is not destroyed, but accumulates and
brings about increased synthesis of LuxR protein which causes light production by activating the
luxCDABE genes, exactly as in the Vibrio fischeri example above (example 1). Thus, we have the
Vibrio fischeri system with added controls.
Why use three autoinducers?
The three signals and three receptors may work as coincidence detectors. It is possible that another
species of bacterium can produce a signal molecule similar enough to CAI-1, for example, to activate
this circuit by accident. By requiring three unique signals or three unique keys, the bacteria can be
sure that they are really listening to signals from their own species - they have an added level of
security to avoid false alarms as all three receptor must be activated simultaneously for a sufficient
response - something which is highly unlikely to occur by chance. Such devices can be important in
the busy world of bacterial communication where signals can get confused (like wires getting crossed)
and where some bacteria will also try to jam or otherwise exploit the signals of others. Since these
three circuits operate together, side by side, we say that they operate in parallel.
Several quorum sensing circuits operating in series
Our fourth example adds a bit more complexity! We look at the Gram negative bacterium
Pseudomonas aeruginosa, which occurs almost everywhere - in water, in soil and can cause disease
in people whose immune systems are weakened. Once again, quorum sensing is essential for this
organism to invade the human body and cause disease.
This bacterium emits two quorum signalling molecules: LasI (similar to LuxI) synthesises a AHL signal
molecule, which I have called AHL-1 and RhlI synthesises another AHL, which I have called AHL-2.
Thus we have two Lux-like circuits. AHL-1 binds to its receptor protein, LasR, whilst AHL-2 binds to the
receptor protein RhlR. RhlR is a DNA regulator (the R on the end of these protein names means
regulator) as it binds to a DNA switch (when bound to AHL-2) causing transcription of the genes
encoded in the Rhl regulon.
Here is the added complication - the LasR regulator also activates the genes encoding the synthesis of RhlI
and RhlR and so the LasR must be activated by AHL-1 before the cell can respond to AHL-2, that is the two
circuits work in sequence (or in series). This induces a time delay between activation of the first circuit and
activation of the circuit circuit, which is assumed critical to the timing of events during infection - the genes
activated by the second circuit are required later in the infection sequence and are only produced if the
infection proceeds through the first stage which involves the genes controlled by the first circuit (in the Las
operon).
Quorum quenching
Finally, without going into too many details, it is worth pointing out that different species of bacteria may
tamper with the communication systems of rival species and so dampen down or quench the quorum
response of their rivals. For example, one species may destroy the signal molecules of a rival species that
lives in the same habitat, effectively jamming the signals of its rival. Bacteria also possess means of turning
down their own communication systems.
Summary
We have looked at some of the communication systems of bacteria, all of which enable bacteria to work
together with other members of their own species (and sometimes with other species, some bacteria also
communicate with plants when both these creatures need to work together). The strength of the signal
(called an autoinducer) increases as the cell population increases in density. This allows bacteria to switch
on systems that require a large number of bacteria to work together, such as producing light or invading the
human body. These signals work by binding to specific receptors which then switch certain genes on or off
and so change the behaviour of the bacteria. This involves a series of secondary signals inside the cell,
which pass signals from the receptor to the genes. Several such systems are usually connected together or
connected with other sensory and signalling systems that we have not mentioned, producing a very complex
network of signals inside the bacterial cell, which work with the DNA as a computer processor, receiving
information from the environment and processing this information to determine the most appropriate
response.
In bacteria the total complexity of these systems exceeds what we have seen here by about 100-fold. In
animal cells, the signals are probably 10 times as complex again. This makes deciphering the inner workings
of these biological communication and information processing systems immensely difficult - cell signalling is
one of the most difficult and complex disciplines in the whole of modern science. The additional complexity of
these systems in plants and animals, enable their cells to build more complex bodies than those slime cities
of the bacteria, and is the principle difference between them. To achieve this extra complexity, plants and
animals require more genes than bacteria. For example, humans have about 5 times as many genes (25
000) as a typical bacterium (about 4000 -5000).
and RhlR and so the LasR must be activated by AHL-1 before the cell can respond to AHL-2, that is the two
circuits work in sequence (or in series). This induces a time delay between activation of the first circuit and
activation of the circuit circuit, which is assumed critical to the timing of events during infection - the genes
activated by the second circuit are required later in the infection sequence and are only produced if the
infection proceeds through the first stage which involves the genes controlled by the first circuit (in the Las
operon).
Quorum quenching
Finally, without going into too many details, it is worth pointing out that different species of bacteria may
tamper with the communication systems of rival species and so dampen down or quench the quorum
response of their rivals. For example, one species may destroy the signal molecules of a rival species that
lives in the same habitat, effectively jamming the signals of its rival. Bacteria also possess means of turning
down their own communication systems.
Summary
We have looked at some of the communication systems of bacteria, all of which enable bacteria to work
together with other members of their own species (and sometimes with other species, some bacteria also
communicate with plants when both these creatures need to work together). The strength of the signal
(called an autoinducer) increases as the cell population increases in density. This allows bacteria to switch
on systems that require a large number of bacteria to work together, such as producing light or invading the
human body. These signals work by binding to specific receptors which then switch certain genes on or off
and so change the behaviour of the bacteria. This involves a series of secondary signals inside the cell,
which pass signals from the receptor to the genes. Several such systems are usually connected together or
connected with other sensory and signalling systems that we have not mentioned, producing a very complex
network of signals inside the bacterial cell, which work with the DNA as a computer processor, receiving
information from the environment and processing this information to determine the most appropriate
response.
In bacteria the total complexity of these systems exceeds what we have seen here by about 100-fold. In
animal cells, the signals are probably 10 times as complex again. This makes deciphering the inner workings
of these biological communication and information processing systems immensely difficult - cell signalling is
one of the most difficult and complex disciplines in the whole of modern science. The additional complexity of
these systems in plants and animals, enable their cells to build more complex bodies than those slime cities
of the bacteria, and is the principle difference between them. To achieve this extra complexity, plants and
animals require more genes than bacteria. For example, humans have about 5 times as many genes (25
000) as a typical bacterium (about 4000 -5000).
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