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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