Speaking the language of bacteria

Microbial geneticist Prof Bonnie Bassler of Princeton University is a sort of bacterial linguist -- she studies how bacteria, the simplest living organisms, communicate.

In fact, it seems bacteria evolved an efficient communication system several billion years before humans invented telephones, radio and the Internet.

"People thought for the past 100 years that bacteria lived solitary, reclusive lives, but it now seems that all bacteria communicate with hormone-like signalling molecules," Bassler said.

In Melbourne yesterday, Bassler described to the ASM 2002 conference how a microbe can tell whether it is alone or in friendly company, or confronting potential rivals. The signals activate receptors that allow the microbe to cooperate with its peers, or take defensive action.

Bassler has been listening in on this "bact-chat", and has found that each species has its own species-specific signals.

"Bacteria talk to each other," says Bassler. "They can detect when they are alone, or in communities, by sensing the level of these signalling molecules in the environment.

The phenomenon has been dubbed 'quorum sensing' -- "The concentration of the signalling molecules correlates with the number of bacterial cells in the population," says Bassler.

"The bacteria respond by changing gene expression, which changes their behaviour. It allows them to carry out certain behaviours only when they are at high population densities, such as secreting toxins, activating virulence factors that allow them to infect their hosts, or to form complex communities that produce biofilms on surfaces.

"If a single bacterial cell enters your body, it gets creamed by the immune system. If it waits until it has company, it can win the war and infect its host -- it's a fantastic survival strategy."

Prefiguring higher life forms

The intracellular communication system that has made bacteria such successful organisms prefigures the intricate intracellular signalling systems in higher life forms.

New drugs that would disrupt these bacterial signals could be powerful weapons against infection, according to Bassler.

But six months ago, the Princeton researcher made a spectacular discovery that could yield a decisive weapon for the perennial war between humans and their microbial pathogens.

She found that, in addition to their own species-specific 'dialects', bacteria also possess a universal signalling molecule: a sort of microbial equivalent of Esperanto.

The signalling molecule, called furanosyl borate diester, appears to be identical in all bacteria, even on opposite sides of the ancient evolutionary divide between gram-positive and gram-negative species.

The molecule is unique: it consists of two sugar-like ring molecules, linked by a boron atom -- the first biologically active molecule in nature known to incorporate boron atoms.

As all bacteria share this single, unique signalling molecule, it's an outstanding target for new drugs that would quell bacterial infections by jamming the most basic signalling system that bacteria use to communicate.

And because furanosyl borate diester is exclusive to bacteria, and does not occur in complex, multicellular life forms like plants or human beings, drugs that target it are unlikely to have toxic side-effects in humans, says Bassler.

Developing drugs

"We've figured out its the exact structure, so we can now try to make a drug that resembles it, to block the receptors that allow bacteria to receive the signal," she says. "A second strategy would be to develop drugs that would disrupt enzymes that are involved in making the molecule."

The advantage of a drug that prevented bacterial infections by disrupting quorum sensing is that it would apply only 'soft' selection pressure to the bacteria -- it would sow confusion, rather than killing the cells.

In the absence of the primal signalling molecule, bacteria would not be able to form organised communities, and would remain in an avirulent state.

In contrast, the current generation of antibiotics apply intense selection pressure to bacterial populations, which almost invariably leaves behind a small population of resistant individuals that flourish, and form resistant populions -- this intense selection pressure has been the source of deadly strains of bacteria like MRSA, which have become resistant to virtually all conventional antibiotics.

Bassler says a new US biotechnology company, Quorex, has been established to exploit the discovery.

Genius award

Just before Bassler left for Australia the Macarthur Foundation, a philanthropic trust, rang and asked her if she knew anyone who had won a Macarthur Fellowship, popularly known in the US as a 'genius award'.

Macarthur Fellowships recognise outstanding achievements in public life, and cross the arts and sciences. All nominations are made anonymously, and the first thing that the recipients know about it is when a Foundation representative rings them.

Bassler initially thought she was going to be asked to act as a referee for a nominee -- and was then told that she had actually won a Fellowship, worth $US500,000.