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MICROBE OF THE MONTH: The fleece and the phage: a yarn from down under

A bacterium attacking sheep in Australia may have met its match, says Bernard Dixon
Louis Pasteur, the centenary of whose death falls later this year, would not have understood our present-day compulsion to categorise science as "pure" or "applied". Virtually all the great French chemist's work, on subjects ranging from beer- and wine-making to silkworm disease and anthrax in sheep, fully merited both adjectives. It revealed fundamental features of the biological world, while at the same time served the needs of industry and practicality.

So I like to think that Pasteur would have chuckled appreciatively over a paper in the current issue of Letters in Applied Microbiology. It demonstrates a hitherto unrecognised natural relationship between two different microbes, and also suggests a strategy for controlling a condition that causes substantial problems for Australia's wool industry.

The condition investigated by Douglas Kurtboke and his colleagues in Western Australia is known as lumpy wool, an infection caused by the bacterium Dermatophilus congolensis. It affects merino sheep in particular, though it poses a greater problem by impairing the quality of the wool than by seriously threatening the health of the animals.

D. congolensis invades the sheep's skin follicles, where it multiplies and provokes inflammation. The inflamed skin releases pus, containing the bacterium, which mats the wool, creating "lumpy wool scabs". As the scabs dry, the bacteria form spores to protect themselves from desiccation. When the animal next becomes wet, perhaps after a rain shower, the spores again release bacteria. These infect further skin follicles, initiating the whole cycle once more.

Damp conditions not only facilitate this process of reinfection, but also allow D. congolensis to pass from affected sheep to unaffected ones. Although lumpy wool may be an acute and short-lived condition, it often becomes chronic and can last for a year or more. The scabs downgrade the quality of the fleece, sometimes making it unusable.

Present methods of dealing with lumpy wool leave much to be desired. Penicillin is partially effective, though only when given for lengthy periods. This encourages the development of antibiotic-resistant bacteria, and can leave residues - a potential problem if the meat is intended for human consumption. Chemicals applied externally may fail to reach the bacterium in the hair follicles. Vaccination can promote recovery - without, however, preventing the formation of infectious scabs. In practice, farmers often resort simply to cutting out affected areas of wool and culling badly infected sheep.

Kurtboke and his collaborators decided to explore an alternative approach. Just as bacteria attack humans and other animals, so they in turn are preyed upon by much smaller microbes - viruses known as phages. There is a relationship between a particular phage and the specific bacterium or bacteria that it can invade. Phages also differ in their virulence. Some destroy their prey quickly. Others are comparatively benign, co- existing in a permanent partnership with the bacteria they infect.

By no means all bacteria are known to be susceptible to phages. Moreover, phages are not uniformly distributed. In another parallel with populations of humans and of disease-causing bacteria, a phage that is relatively common in one region may be absent from another environment.

All of this encouraged the Australian scientists to search for a phage capable of attacking D. congolensis. If they found one, they might be able to administer it to infected sheep. A further possibility was genetically engineering such a phage, making the naturally occurring one more virulent by altering its genes or introducing new ones.

The normal method of finding phages is simply by examining environments inhabited by the bacteria upon which they prey. For example, bacteriologists searching for phages capable of attacking Escherichia coli, a common inhabitant of the human bowel, usually screen samples of sewage. The Australians turned therefore to four different sheep farms in Western Australia, where they obtained samples of both infected wool and other materials such as soil.

They tested the specimens by spotting them on to glass dishes containing nutrient medium and D. congolensis, the prospective target for phage attack. Wool from three of the farms proved negative, as did all the soil and other materials. After incubation, the dishes showed D. congolensis growing over the entire area, unaffected by the added specimens. But the fourth farm's wool was positive. It produced clear circles in the nutrient medium where a phage from the wool had invaded and destroyed the bacterium.

Kurtboke and his colleagues confirmed their discovery when they examined the specimens under the electron microscope and saw a previously unknown type of phage. Further tests showed that it was highly specific, attacking D. congolensis but not one of 39 other species of bacteria tested.

The investigators added the phage to samples of ground scab from infected sheep, and found that it reduced the population of D. congolensis to less than a third of that without phage.

The phage's specificity would be a big advantage in its use for combating the microbe responsible for lumpy wool. It would be unlikely, for example, to attack beneficent bacteria. Above all, such a natural, biological approach would be preferable to the use of antibiotics or other chemicals, with their attendant risks of residues and resistance. Pasteur would have appreciated that.