The sniffling sheep

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. He's also interested in using topical EDTA, which veterinarians already use to treat ear disease and sinusitis. He's recently been in communication with a vet from the University of Queensland, who has shown that topical EDTA is not ototoxic in dogs. Within the next couple of months, Psaltis and his colleagues are planning to begin trials of possible treatments in the sheep. "Some of the possible treatments have proved to be very exciting in the lab," says Wormald. "Now we need to see how they do in the animal model."

The sniffling sheep

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