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Paul Williams talks with
ScienceWatch.com and answers a few questions about
this month's Fast Moving Fronts paper in the field of
Microbiology.
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Article: Quorum sensing, communication and
cross-kingdom signalling in the bacterial world
Authors: Williams, P
Journal: MICROBIOLOGY-SGM, 153: 3923-3938 Part 12 DEC
2007
Addresses: Univ Nottingham, Inst Infect Immun & Inflammat,
Ctr Biomol Sci, Nottingham NG7 2RD, England.
Univ Nottingham, Inst Infect Immun & Inflammat, Ctr Biomol
Sci, Nottingham NG7 2RD, England.
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Why do you think your paper is highly
cited?
This paper focuses on a "hot topic" in microbiology, namely 'quorum
sensing,' i.e., the extraordinary capacity of unicellular microorganisms to
behave socially by coordinating gene expression at the population level
through the deployment of small diffusible signal molecules.
It provides a perspective primarily on N-acylhomoserine lactone
AHL-mediated quorum sensing with a focus on prokaryotic-eukaryotic
interactions and the specific responses of the latter to AHL signal
molecules.
Does it describe a new discovery, methodology, or
synthesis of knowledge?
This paper is a synthesis of some of the quorum sensing research which my
laboratory has undertaken for over almost the past 20 years, and for which
I was awarded the Society for General Microbiology Colworth Prize Lecture,
delivered at their 160th meeting on March 28th, 2007.
The article outlines my scientific contribution to the discovery of quorum
sensing systems in diverse bacteria with a focus on plant-microbe
interactions and the impact of quorum sensing signal molecules on the cells
and tissues of higher organisms.
Would you summarize the significance of your paper
in layman's terms?
The discovery of the ubiquity of quorum sensing systems has completely
changed the way in which we view microorganisms. No longer can we view
bacteria as simple selfish individual cells striving only to divide and
multiply.
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"Quorum sensing systems are not only providing us with
new fundamental insights into the social behavior of single
and multiple species microbial communities but also provide
new insights into evolutionary questions with respect to
cooperation, communication, and altruism."
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We now appreciate that, for microbes, communication and teamwork are just
as important as competition in the race to colonize new environmental
niches, exploit available food resources, and combat threats such as
predatory higher organisms and host immune defenses. With this new
understanding come new opportunities for exploiting beneficial bacterial
behavior and blocking adverse microbial activities.
How did you become involved in this research and
were any particular problems encountered along the way?
In the late 1980s, I was working in collaboration with my colleagues Barrie
Bycroft (at the University of Nottingham, UK) and George Salmond (then at
Warwick University, UK) on the biosynthesis and regulation of carbapenem
antibiotics in the plant pathogen, Erwinia carotovora.
Our strategic goal was to develop a biosynthetic alternative to the
expensive industrial scale total chemical synthesis for this valuable class
of antibiotics. By selecting for mutants unable to make the carbapenem, we
hoped to identify the biosynthetic genes and gene products involved. Within
this mutant bank, we identified a carbapenem-negative mutant class, in
which antibiotic production could be restored by mixing with a second class
of mutant.
Subsequent experiments revealed that the latter were producing a diffusible
molecule which triggered antibiotic production in the former. After
purifying a molecule which we presumed would be a biosynthetic
intermediate, we were surprised to discover that it bore no structural
resemblance to the carbapenem nucleus but instead was an AHL signal
molecule, N-(3-oxohexanoyl)homoserine lactone (3O-C6-HSL).
On searching the literature, we discovered that 3O-C6-HSL was known and, in
fact, was used by a completely unrelated marine bacterium (Vibrio
fischeri) to regulate bioluminescence. For two such different
terrestrial and marine organisms to share a common signalling molecule
suggested we had stumbled upon something new and exciting: a widespread
bacterial communication language.
We were able to quickly build on our serendipitous findings since we had,
at the University of Nottingham, an international expert on bacterial
bioluminescence, the late Gordon Stewart. He had constructed a light-based
reporter system which could be exploited for the rapid screening of other
bacterial species for the presence of 3O-C6-HSL.
This resulted in the discovery of many more AHL-producers, including
important human pathogens such as Pseudomonas aeruginosa.
Where do you see your research leading in the
future?
Quorum sensing systems are not only providing us with new fundamental
insights into the social behavior of single and multiple species microbial
communities but also provide new insights into evolutionary questions with
respect to cooperation, communication, and altruism.
A better understanding of the molecular nature of quorum sensing systems
offers opportunities for harnessing beneficial bacterial community behavior
or inhibiting pathogenic behavior; for example, in agriculture (control of
plant pathogens and use of bacteria as biocontrol agents), medicine (as a
means of diagnosis, or to monitor treatment), and industry (secondary
metabolite production, microbial detection).
Quorum sensing systems in pathogens represent an exciting target for novel
antimicrobials. These will attenuate virulence rather than kill, a feature
which should hugely reduce the selective pressures associated with
bactericidal agents which leads to the rapid emergence of resistance.
Paul Williams
Professor of Molecular Microbiology
Head, School of Molecular Medical Sciences
Centre for Biomolecular Sciences
University of Nottingham
Nottingham, UK
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KEYWORDS: ACYL-HOMOSERINE-LACTONE; N-ACYLHOMOSERINE LACTONES; CARBAPENEM
ANTIBIOTIC PRODUCTION; TO-CELL COMMUNICATION; PSEUDOMONAS-AERUGINOSA;
ERWINIA-CAROTOVORA; N-(3-OXODODECANOYL)-L-HOMOSERINE LACTONE;
N-(3-OXOHEXANOYL)-L-HOMOSERINE LACTONE; STRUCTURAL IDENTIFICATION;
VIRULENCE DETERMINANTS.
