The end of the
AGP paradigm?
Cutting-edge technology offers the opportunity to control the micro-organisms in the
gastrointestinal tract of poultry. Could ‘quorum sensing’ succeed the industry’s use of
antibiotic growth promoters within the next decade?
Today, there is an industry-wide understanding that the
interplay between animals
and the bacteria that live within
their gastrointestinal (GI) tract is
highly complex. The GI tracts of both
monogastric and ruminant animals
contain beneficial bacteria that
contribute to the health and nutrition
of the animal as well as deleterious
species that deprive the animal of its
nutrients or, worse still, cause disease.
The GI tract contains a diverse ecology
of micro-organisms, all competing for
reproductive advantage. Control of this
gut flora has been a most useful tool in
modern agriculture both in terms of
performance and animal health.
Historically, antibiotic growth
promoters (AGPs) have targeted
those types of bacteria that share a
common characteristic. Most in-feed
AGPs select against gram-positive
bacteria although some of this group
Chemical structure of the new
molecule, OHHL
Results of a broiler trial comparing a
control diet with one containing OHHL
(mean 21-day bodyweights; g)
800
Bodyweight (g)
780
760
740
720
700
Control
OHHL
contribute to the overall health of the
animal. For example, both lactobacilli
and bifidobacilli are gram-positive
and, indeed, are frequently found
in probiotic additives. Equally,
formulations designed to promote and
nourish beneficial bacteria very often
support pathogenic bacteria just as well
as the intended recipient. These are
in-built limitations on the effectiveness
of our current strategies: the use of
antimicrobial agents – natural or
otherwise – is a hit-and-miss approach.
New technology cracks
the communication code
Recent advances in microbiology
suggest that an entirely new group of
molecules may offer a way of precisely
targeting individual species of bacteria
and allow the promotion of beneficial
micro-organisms while at the same
time diminishing the threat from
pathogens. Bacteria have been found
to possess a communication system,
called ‘quorum sensing’, that gives
them the benefits of co-operation
using small molecules to ‘talk’ to
each other. These molecules, called
auto-inducers, are signal molecules
that activate or de-activate different
behaviours of bacteria. For example,
a particular auto-inducer may cause
one species to express surfactants,
toxins or to attack another species
using defence chemicals. Another
auto-inducer may ‘switch off’ those
same behaviours. Bacteria have evolved
these sophisticated trigger mechanisms
so that recognition of, and reaction
to, their own cell densities and the
population of competing types of
bacteria is possible. A good example
is the light-emitting bacteria that live
symbiotically on certain deep sea
jellyfish. Here, the bacteria are able to
flash on and off en masse providing
David Garnett
a defence for the host. This would be
impossible without a communication
circuit between the millions of bacteria
required to produce a visible light.
In just the same way for individual
bacteria in the gut, switching on or
off virulence factors in isolation will
have a negligible overall effect but a
co-ordinated attack of many millions of
cells can profoundly alter the balance
of power in the gut.
So far, a couple of dozen signals
have been identified although the
interaction of these compounds in
mixed bacteria populations is less
well understood. One problem in
the elucidation of these interactions
is that any particular auto-inducer
may act as both an antagonist and an
agonist depending upon conditions
and isomeric structure. Most of the
research carried out on these chemicals
has been focused on ways to use them
in medical science. There is hope
that this work will reveal new ways of
dealing with intractable infections such
as methicillin-resistant Staphylococcus
aureus (MRSA), which causes a
significant number of deaths each
year in hospitals as the result of poor
hygiene following surgical procedures.
Using the technology
in poultry feed
Once auto-inducers had been
discovered functioning in the gut of
animals, it was only a matter of time
before scientists attempted to control
gut bacteria artificially by adding
additional signal molecules to the
feed. It has now been shown that one
such signal oxo-hexanoyl homoserine
lactone (OHHL) can increase dry
matter digestion in ruminants. It was
also shown to have lowered mortality
and increased daily growth in poultry,
as shown in the accompanying table