Science: Bugged by a critical mass

New research shows that certain bacteria behave strangely in a group. Bernard Dixon reports

Would you agree that bacteria are simple, senseless, essentially solitary cells which live and die alone - unlike our own cells, for example, which are enmeshed in a web of chemical communication with other tissues and organs? Like several other people, I held this view, and propounded it in many articles and books over the years. It now turns out to be fallacious.

Recent discoveries show that some bacteria, at least, live in communities where they sense the environment and the presence of their peers, and respond in a variety of ways conducive to the common good.

One means of microbial communication that is attracting keen interest among bacteriologists is called "quorum sensing". Imagine a committee of 12 smokers that meets regularly in the back room of a pub. If only four or five turn up for a meeting, they hardly notice the smoke in the air. But with seven or more present, there is soon a move to open a window: at some point the smoke will become dense enough to trigger a unanimous demand for ventilation. Whatever the committee's statutes say, it is the quorum of seven which determines what happens.

Quorum sensing by bacteria works in the same way. A few years ago, researchers found something odd about Photobacterium fischeri, a microbe that can emit blue-green light. It does not do so (or at best glows dimly) when the cell population is relatively scanty. A dense population, on the other hand, generates quite a dazzle. The surprising discovery was that the amount of light is not directly proportional to the size of the community. Instead, there is a population size - a quorum - above which all of the bacteria begin to emit much more light than they did before.

The cause is a rather neat feedback mechanism. Whether in a scanty or dense community, P. fischeri produces an "auto-inducer" chemical which can switch on genes in the bacterium that make it luminesce. But the auto- inducer must reach a particular level before it works. When that concentration is attained - by the right quorum of cells - then the lights go on throughout the population.

Quorum sensing by P. fischeri reflects its two alternative lifestyles. It can grow freely in the sea, where the density of its population is very low and where it does not luminesce. However, evolution has also produced an arrangement in which the light organs of certain squids and fishes can house the bacterium.

When P. fischeri takes up residence in a young fish, it proliferates quickly, producing auto-inducer which soon hits the level to make the entire community begin to generate light. The bacterium gains a protected environment; the fish gains a source of light, with which it can communicate with other fish. Any bacteria that pass back into the sea soon stop luminescing, as the level of auto-inducer declines. Since generating light uses energy, the bacteria clearly benefit by not continuing when there is no longer any advantage in doing so.

The most recent example of quorum sensing, discovered by Clay Fuqua and colleagues at Cornell University, is very different - though identical in principle. They have studied Agrobacterium tumefaciens, which produces tumours known as crown galls on oak trees and other plants. The bacterium can do so only if it contains a tumour-inducing (Ti) plasmid - a loop of DNA - carrying the relevant genes. When the bacterium infects a plant, the genes leave the plasmid, enter the plant's chromosomes and initiate tumorous growth.

Like P. fischeri, A. tumefaciens produces an auto-inducer, whose threshold effect is to increase the rate at which the Ti plasmid spreads from one bacterium to another. Auto-inducer builds up when the bacteria are able to grow well, because they find particular nutrients in their environment. If the circumstances are favourable for the bacteria to invade the plant, it is desirable that as many members as possible are quickly armed with the plasmid.

Another example occurs in Pseudomonas aeruginosa, a bacterium that is often harmless but can cause serious infections in patients who are already seriously debilitated. It attacks the body by producing substances such as haemolysins, which smash open red blood cells. But the bacterium synthesises these chemical weapons only when there is a sufficiently dense population for infection to occur. Likewise, certain other microbes produce antibiotics only after their population has reached a critical size.

The big question is whether biotechnologists put this knowledge to good use. Can they design drugs to antagonise the auto-inducers that otherwise trigger haemylosin production by Ps. aeruginosa? Can pharmaceutical companies trick their bacteria into making antibiotics more readily that at present? If so, those rewards will have originated in research driven not by the hope of practical applications but by sheer curiosity.

Dr Bernard Dixon is the author of 'Power Unseen - How Microbes Rule the World', published recently in paperback by Spektrum/WH Freeman