A Quorum Detected

By Jason Socrates Bardi

Words, like people, sometimes get their 15 minutes fame. This was the case recently for the word quorum, which in Latin means "of whom."

Last summer, a group of Texas politicians put this word into the vernacular when they fled the state, eliminating the quorum—the minimum number of representatives needed in a legislative chamber to bring an issue to a vote—and avoiding a controversial redistricting decision.

The word "quorum" is also used in association with bacteria. What do bacteria and Texas state politicians have in common? For one thing, they have both learned one of the golden rules of survival—the great advantage of banding together.

In bacteria, a quorum is the concentration of bacterial cells needed before the population of cells takes some decisive action together—such as producing a "biofilm" of polymers to cover the colony and protect it from threats, or releasing a toxin to suppress the host organism's immune system.

In the last decade, scientists have become increasingly interested in understanding how bacteria communicate with one another to act together in these ways as this may provide alternative strategies for defeating bacterial infections and the problems associated with baterial resistenceIn an emerging area of research called quorum sensing, bacteria are seen not as the single entities of old but rather as a functioning cooperative capable of communicating via small molecules much as insects use pheromones.

A number of the surface receptors that detect these small molecules have been discovered and cloned, but the small molecules themselves have been more of a challenge to identify because they are hard to detect and sometimes impossible to purify from bacterial cultures.

A few years ago, a group at Princeton University discovered a small quorum-sensing molecule that bacteria produce called AI-2, and the group proposed a pathway for its biosynthesis within the bacterial cells that included the formation of a precursor molecule called DPD. The involvement of DPD in quorum sensing has been a matter of debate ever since.

Recently, Professor Kim D. Janda and Research Associate Michael Meijler of The Scripps Research Institute set out to determine the involvement of DPD in quorum sensing, and in the latest issue of the journal Angewandte Chemie, they report positive results.

In their study, Meijler and Janda managed to synthesize the precursor molecule DPD and subjected bacterial cells to it. The quest for a synthetic route was difficult and took many months because DPD is a fragile molecule. But in the end, Meijler and Janda succeeded in synthesizing it and verified its activity in quorum sensing.

Their experiment used an assay produced by Bonnie Bassler at Princeton, involving bioluminescence—the production of visible light by the bacteria. In the assay, bioluminescence occurs when there is a sufficient density of cells (a quorum). In their study, Meijler and Janda tricked the bacteria into thinking that they were at a high density by adding the DPD. When they did this, the bacteria began to glow at low cell density as if there was a quorum.

Now that they have synthesized the direct precursor to AI-2, Meijler and Janda can start synthesizing analogues (compounds that are chemically related) and see how effective these are at inhibiting quorum sensing. If analogues could be found that do inhibit quorum sensing, then these analogues might be useful starting points for developing a next-generation antibiotic.

To read the article, "Synthesis and Biological Validation of a Ubiquitous Quorum Sensing Molecule" by Michael M. Meijler, Louis G. Hom, Gunnar F. Kaufmann, Kathleen M. McKenzie, Chengzao Sun, Jason A. Moss, Masayuki Matsushita and Kim D. Janda, see the April 16, 2004 issue of Angewandte Chemie or go to: http://www3.interscience.wiley.com/cgi-bin/jhome/26737.


Send comments to: jasonb@scripps.edu









Professor Kim D. Janda and Research Associate Michael Meijler set out to determine the involvement of DPD in quorum sensing, and, in the latest issue of the journal Angewandte Chemie, report positive results.