Alkis Psaltis has seen more than his share of sheep with the sniffles.
Over the past year or two, in the course of researching the role of
bacterial biofilms in sinusitis, woolly ruminants with nasal congestion
have become almost a daily event for the scientist at the Queen
Elizabeth Hospital in Adelaide, Australia. "Basically, the sheep get
runny noses," Psaltis explains. "They get a purulent discharge and all
the signs of an inflammatory response, including frank pus and friable
mucosa."

Psaltis and his colleagues have developed a sheep model for sinusitis
that they are using to investigate how biofilms are implicated in the
development of chronic sinusitis. Their research could pave the way for
better treatments.

In recent times, it has become increasingly clear that bacterial
biofilms cause some of the more stubborn conditions that affect the ear,
nose, and throat, including glue ear and chronic rhinosinusitis. Nestled
deep within their slimy matrix, these biofilms (slow-growing bacteria)
are protected chemically and physically from the outside world, making
them as much as a thousand times more resistant to antibiotics than
their free-living cousins.

Researchers wanting to study these systems in vivo have faced a problem.
The only available animal models for sinusitis didn't mimic the human
situation closely enough. So Psaltis and his PhD supervisor, Peter-John
Wormald, turned their attention to sheep. "The good thing about sheep is
that they have a similar sinonasal anatomy to humans," he explains.
"They also suffer a similar disease spectrum to us, including sinusitis
and allergic rhinitis."

Another benefit of using sheep is that their frontal sinuses are located
not far under the skin, making it easy to access them via a small hole
known as a minitrephine. Psaltis has been using these openings, which
are also used in humans for treatment of sinusitis, as a way to
inoculate the sheep with bacteria and to examine the subsequent infection.

These castrated Merino-cross sheep that Psaltis uses in the studies, can
tolerate anesthetic fairly well. "Pigs, for example, don't tolerate
anesthetic nearly as well and are more expensive to keep," Psaltis says.
Indeed, Wormald has been using sheep for five or six years to study
other aspects of the nasal system, including wound healing after surgery.

With the model in place, the Australian researchers have begun trying to
correlate the creation of bacterial biofilms in the sheep sinuses with
the signs of sinusitis. To do this, Psaltis introduced cultures of
free-floating or planktonic Staphylococcus aureus into sheep whose
sinuses had been blocked with cotton-wool to mimic the conditions of
chronic sinusitis. S. aureus is the most commonly identified bacterium
in human patients with chronic sinusitis, Psaltis says.

Within days, the signs of the infection appeared, at which point the
sheep were killed and their sinuses examined for the presence of
biofilms using confocal scanning laser microscopy. "What we found was
that the planktonic bacteria we introduced had adopted the more stable
form of a biofilm in response to the environment - a closed sinus
without much oxygen," Psaltis says.

Now the investigators are beginning to work on therapeutic approaches
that will break down the biofilm and succeed where antibiotics often
don't. Psaltis has had one paper on the subject accepted for
publication, and another on the way. "I think the hallmarks of a
successful treatment would be anything that can disrupt the scaffold or
matrix of the biofilm, whether that's mechanically or biologically," he
says.

Harvey Coates, a senior ear, nose, and throat surgeon at Princess
Margaret Hospital for Children in Perth, Australia, says the model is
impressive. "It's great ... to have a direct model to work on such as
this one." Coates studies the role of biofilms in middle ear infections.
He suggests that one approach to treatment might be to disrupt the
intracellular signalling that goes on within biofilms.

http://www.the-scientist.com/article/home/52957/