Communication has always been the essence of life on earth. It is the method by which living creatures gain access to information regarding the world around them, that is profitable to their well-being - where the food is, what predators are lurking at the boundaries of the territory, which members of the opposite sex are ready to take on a partner.

To simply describe communication as the transference of information from one party to another would be to rob it of its richness and colour. Far from being the mere trickling of data, communication - from the trumpeting of an elephant to the mating dances of birds to the songs of humpback whales, to even the Internet culture that has pervaded our society - is a means of letting the rest of the world into our personal universes, of removing boundaries and creating bonds, a means of ensuring that no living creature exists as an island.

Would it, then, surprise you to learn that microorganisms are also capable of communication?

Small talk

Oh yes, microbes talk - although their form of communication is so alien that many of us would not even recognise it as such. You see, microbes communicate by using chemicals.

Why the need to talk to one another?

No microbe is an island - not if it wishes to survive in an environment that is not hospitable to it. In order to survive, a microbe needs to have information regarding their environment - how much food is available, whether there are any toxins that it should avoid, what predators are out there - and be able to respond quickly to it. A pathogen that does not know when the host's immune system is out to get it is not going to live very long or achieve very much.

So how do microbes talk?

Microbes communicate with one another by releasing and sensing chemicals called pheromones. Pheromones have long since been identified in animals as chemicals responsible for stimulating certain behaviour and reactions. Microbial pheromones are divided into two categories - isoprenoids and peptides. Isoprenoids, the more common of the two, are composed of repeating chains of hydrocarbon* called isoprene*. One typical example of isoprenoid pheromones are steroids. which are made up of six isoprene units joined in a straight chain to form cholesterol, which is the foundation for the synthesis of all steroids. Peptides, on the other hand, are composed of amino acids, which are the building blocks of all proteins. In some cases, pheromones consist of peptides linked to an isoprenoid.

These chemicals are synthesised by the microbes themselves, and are secreted by them when the need to communicate arises. These chemicals are then picked up by other microbes, which will assess its concentration levels. Once a critical concentration of this chemical has been established, a positive-feedback mechanism kicks in and causes an increase in the synthesis of this chemical, triggering an increase in whatever the activity this pheromone initiates. (You can think of these pheromones as a kind of chain-reaction switch mechanism)

Of course, different microbes may use different signalling chemicals, which means that a bacteria will not necessarily understand what a mold is saying. Of course, there is evidence of cross-talking, but not everybody is capable of that.

A World Without Sound

Why, you ask, do these microbes go through the bother of synthesizing and sending out chemicals? Wouldn't it be so much simpler to communicate by sound, as most of us do?

Not quite. Microbes are at a severe disadvantage where sound production is concerned. In the first place, to be able to produce sound, you would need equipment that is at least as big as the wavelength of the sound you are producing. Being terribly minute creatures (a typical bacteria is about 2 microns - 0.000002 metres - long), microbes would only be capable of generating sounds of very short wavelength, would effectively come out as a million-hertz squeak*. Sound aesthetics aside, these high-frequency sounds would have severe difficulty travelling over distances of more than a few centimeters because water or liquid, the common habitat of microbes, absorbs high frequency wavelength very strongly - which would do our poor exhausted microbe no good.

Even if a microbe were capable of producing sound, there would be the problem of detecting the sound. Anyone who has ever tried to shout to a friend while underwater will know just how hard it is to convey the sound over a distance of as short as two metres. This is because sound is a mechanical wave created by molecules moving back and forth in a coordinated motion, producing alternating high- and low-pressure densities that can travel many metres. The sounds are picked up by detecting the relative motion of low- and high-inertia structures in the animal body, such as the ear. However, as viscosity dominates inertia in the microbes' waterworld, there is no effective way for them to detect sound.

And even if they could detect sound, what would they make of it? Being such tiny microbes, they are forever being bombarded by molecules. With all that rattling of their cellular structures, it would take a miracle for the microbe to distinguish between movement due to sound and movement caused by this incessant pounding.

No, the microbes are better off deaf and dumb.

How did scientists figure out that microbes were talking to each other?

It all began one fine day in the 1960s when it was observed that cultures of the marine bioluminiscence bacteria Vibrio fisheri was discovered to fluoresce only when large numbers of the organism were present. Intrigued, the scientists sought to explain this puzzle. They initially thought that there were things in the culture media that was inhibiting the bioluminiscence, which was removed when there were sufficient cells; they later found out that this was due to the accumulation of an activator molecule or "autoinducer", which activates the bioluminiscence when the concentration is high enough. The scientists called this phenomenon "Quorum Sensing*".

For many years, it was thought that only marine bacteria such as V. fisheri and V. harveyi were capable of quorum sensing. However, research carried out in Nottingham and Warwick in the 1990s soon showed that there were far more microorganisms capable of quorum sensing than previously thought. Barrie Bycroft, Paul Williams and George Salmond were studying mutants of the plant pathogen Erwinia carotovora that were unable to make carbapenem antibiotics. They found that one class of mutants were unable to synthesize the antibiotics on their own; however, when cross-fed by a second group of mutants, they gained the ability to do so. Studies revealed that this second class of mutants was supplying a signal molecule which triggered antibiotic synthesis in the first class of mutants. What was even more amazing was that this molecule was the same as the one used by V. fisheri to induce bioluminiscence.

Intrigued, these researchers joined forces with Gordon Stewart from the University of Nottingham, and the rest, as we say, is history.

What do microbes say to each other?

Obviously, microbes don't make small talk the way we do. For one, they certainly don't have the resources, and even if they could, what would they say to each other*? Microbes are not very social creatures - except with regard to one aspect of their lives, which will be discussed shortly - and will only communicate with one another when the need arises.

1. We want food

One of the most peculiar discoveries about the nature of microbes is that some of them are actually capable of bioluminiscence. In other words, they glow. And in most cases, inside fish.

The first question normally asked is - why have microbes evolved to be capable of bioluminiscence? Fireflies glow to attract mates. Some species of fish fluoresce to mask the shadows they would otherwise cast upon the sea bed. What purpose could bioluminiscence possibly serve microbes?

In the past, some scientists had thought that bioluminiscence was a way for microbes the rid themselves of excess energy. Now, however, some are proposing that it may serve a symbiotic purpose - that the microbes provide illumination for their fish symbionts to find food (the bacteria Photoblepharon steinitzi are located in the light organs of the flashlight fish Anomelops) in return for nutrients and dispersal - the microbes cast light on food, the fish eat the food, and the microbes are dispersed through the alimentary route.

The discovery that microbes do not glow at all times may cast light upon this matter. Not all microbes live in the intestines of fish or other organisms. Some are found on decaying organic matter. If microbes were in fact glowing to rid themselves of excess energy, their bioluminiscence would be random and erratic. But scientists have found that these microbes only glow when iron supply is low (microbes need iron for many biochemical reactions) and go dark when they have enough iron. They hypothesize that these iron-starved bacteria living on detritus gain access to the much-needed metal inside the intestines of fish. In which case, it would be roughly the microbial equivalent of saying, "We're starving! Feed us!", or, alternatively, a microbe con-job - duping the fish into thinking the microbes were good to eat, thus bringing them into their system.

Perhaps the best evidence that the microbes are interacting with one another is this: no bacteria fluoresces when it is alone. They will only glow when there is a whole clump of them - what use is there glowing when no one will see your light?

And how do they do this? By assessing the concentration of pheromones in the water.

2. Get off my turf!

Nobody likes having their territory invaded, least of all microbes. Given a choice, the slime mold Dictyostelium would rather keep its distance from neighbours, and if confined, will resort to being dispersed uniformly. Because these microbes have no way of slugging it out, the only civilised way for them to tell each other to stay away is by conveying to others their positions using chemicals. Other microbes pick up the chemicals and subsequently keep their distance. It is not yet confirmed if these chemicals are released solely for this purpose, or if it is a waste product or chemicals accidentally released during some microbial activity.

3. There is strength in numbers

Alternatively, there are some microbes that have 'realised' that they would get things done more efficiently if they were to work with one another, than if they were to work alone. These microbes coordinate themselves so that they carry out certain activities only when there are enough organisms to operate. Our fish story is one example of bacterial cooperation. Likewise, the hospital-infection bacteria Pseudomonas aeruginosa (which causes wound infections and chronic lung infections in immunocompromised patients) only secretes its digestive enzymes when there are enough organisms to make the activity worthwhile. Similarly, the plant pathogen Erwinia carotovora only releases its cell wall-digesting enzymes at high cell density.

4. Let's have sex

Microbes are incredibly social creatures in this respect - and for a good reason too. It is not yet known if sex confers pleasure to the microbes, but it is certainly a good way of acquiring new genetic material for the purpose of adapting to a world that does not welcome them, and for producing offspring that will survive better, or at least remain dormant until conditions become favourable again.

Because asexual reproduction may be favourable over sexual reproduction under certain conditions and vice versa, many microorganisms have developed life cycles to accommodate both reproductive methods, depending on circumstances. When the environment is favourable for growth, a microbe will usually prefer to reproduce asexually - in the case of bacteria and yeast, by binary fission. However, when there are just too many members of the organism in a place where area or food is limiting, the microbe may be forced to reproduce sexually, producing offspring encased in spores that will protect them from the environment, and will germinate when things are right again.

A microbe, unlike most of the sentient lifeforms that have colonised our planet, will not jump at the chance to reproduce with another microbe. Information needs to be obtained about their proximity, the concentration of waste products, how many other microbes are around. All this is usually obtained from other microbes by the methods discussed earlier. And then when a microbe decides to reproduce sexually, there is the matter of the mate.

Finding partners is an abominable task in the microbe world. If you are a free-living, free-swimming microbe, chances are there won't be a mate in the neighbourhood; if you're not motile, you'll probably have a willing partner close by - if you can get to it, that is. And fumbling around aimlessly in the water until you find a potential mate won't help you either.

Many microbes have solved this problem by having one free-moving mating type (male) and one (relatively) stationary one (female.) which will produce a pheromone to attract the other sex. In a study carried out by Terry Snell and David Dusenbery of the Georgia Institute of Technology, it was determined that although the 'male' had no choice but to be motile, the female had three choices: she could be apathetic; she could swim around randomly; or she could devote her energy to pheromone production rather than locomotion. They calculated that devoting energy to pheromone synthesis would get the female a mate a thousand times faster; however, if the organisms were smaller than 0.2mm, the pheromone would difuse away from the female faster than it is synthesized, and therefore locomotion would be more profitable.

What do these microbes do when they encounter one another? In the first place, a member of one mating type has to make sure that his partner is of the opposite mating type to avoid disaster. The rotifer*  Brachionus plicatilis, for example, recognizes a specific glycoprotein molecule on the surface of the female. (To determine if this molecule was in fact the 'marker', Terry Snell and company washed them off females and applied them to agarose beads. As a result, the males attempted to mate with the beads) Once the male makes this identification, copulation will happily occur.

In the case of certain molds, such as the water mold Achlya, the 'female'* mycelium* continually secretes a steroid pheromone called antheridiol. When the concentration hits 0.01 parts per million, the male is stimulated to produce long, thin branches which will grow towards the source of the pheromone. At the same time it will also begin synthesis of a pheromone called oogonial, which will stimulate the female to form spherical branches. Ultimately, these two branches meet, and their nuclei combine to form several spores, each of which contains a new combination of genetic material.

I've got a gene I know you'll like

There are times when a microbe will exchange genetic material with another microbe without undergoing sexual reproduction. This is how bacteria gain resistance to antibiotics - by getting the resistance genes off another bacteria.

Plasmids are small, circular bit of DNA that bob freely in a bacterial cell. These often carry genes that confer resistance to antibiotics or those that will give a microbe the power of virulence in some way> Because of bacterial promiscuity (it seems that they will couple with just about any other bacteria that comes along - and it doesn't even have to be of the same species), these extrachromosomal DNA are passed from bacteria to bacteria almost indiscriminately.

Or is it?

In the laboratory of Don Clewell in the University of Michigan, scientists have found that different plasmids from the bacterium Enterococcus faecalis transfer at different frequencies in liquid. Some of them have transfer frequency as high as one in a hundred donor cells; others transfer so poorly that less than one in a million donor cells is capable of the transfer. It was found that the more efficient plasmids exploited a pheromone produced by E. faecalis cells lacking the plasmids. When donor cells detected the pheromone, they formed protein fibres on their surfaces that enabled to stick to the cells that did not have the plasmid, and subsequently transferred the plasmid to them. Once the recipient cell had the plasmid, it stopped producing the pheromone completely.

6. Let's meet up

Not only are microbes capable of telling each other where they are and coordinating their attacks, they can even call out to each other for the purpose of congregating.

It has previously been discussed that when conditions become unfavourable for a microbe, for instance, when there are too many microbes and not enough food or space, they will reproduce sexually. In the case of the antisocial Dictyostelium discoideum (which, if you recall, hates neighbours and will tell them to stay away), cells that have been living independently of each other will aggregate when there is not enough food to form a large fruiting body that releases spores a few milimetres from the surface. This is to enable the spores, which will germinate to become new Dictyostelium cells, to get to new habitats with ample food supply.

If you were trying to get everybody together, the obvious thing for you to do would be to tell those people in which direction they should move to get to you, or the increasingly big group you are gathering. Dictyostelium does this by briefly secreting a pheromone called cyclic AMP (cAMP). Any other members of its species that happen to be around to catch this signal will fire off a bolt of cAMP in response, and simultaneously produce pseudopodia on the side closest to the source, taking one step in that direction. Detection of this second wave will result in the secretion of a third wave of cAMP accompanied by another step in the direction of the source of the pheromone, and so on.

Of course, pheromones that drift off-course will generate confusion among these migrating cells; therefore, they have solved the problem by evolving an adaptation process that causes to become unresponsive to the cAMP after a few minutes. Meanwhile, the cAMP outside these cells are degraded by an enzyme that is continually produced by the slime mold cells. This causes a decrease in concentration, and allows the cells to regain their sensitivity to the pheromone.

When these slime mold cells are sufficiently close enough to one another, they generate a wave of different cAMP concentration, which will move away from the centres of activity. This causes each member to move in the direction of the higher cAMP concentration at times when the concentration is escalating, and goes on and on until the migrating cells finally find one another (about 10 hours later). This is an example of what is probably the most complicated and incredible feat of microbial communication.

Conclusion

Many of us have gone through life thinking of microbes as simple little creatures leading simple lives. Yet from recent studies we have discovered that these microbes have a great deal more than meets the eye. They were the first to invent rotary motion, they're capable of incredibly complicated chemical-moving processes, small numbers of them can take on a formidable host such as a human being and wreak absolute havoc in the same way David crushed Goliath. And now we have discovered that they are not deaf and dumb and blind at all, but are perfectly capable of communicating with one another. It is clear that these little creatures are far, far more capable of things than we realise.

The next time you see mold on your bread, treat it with a little more respect. Who knows what it may be saying about you...

References

Dusenbery, DB. 1996. Life at small scale: The behaviour of microbes. Scientific American Library, USA.

Webster's Revised Unabridged Dictionary, 1996, 1998 MICRA, Inc.

What is quorum sensing?

Bacterial quorum-sensing structure solved