Vol. 4 Issue 13 / Apr 19, 2004
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
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