An alternative to laboratory mice

June 2, 2000

The discovery that some common diseases use the same genetic tricks to attack different species may prove good news for scientists and laboratory mice alike.

Researchers should now be able to conduct large-scale screening tests to find out which genes give certain bacteria their virulence - as well as those that make their hosts susceptible to attack - using very simple life-forms. This will be far easier, cheaper and ethically more acceptable than using mice.

Work led by Fred Ausubel, a molecular biologist at Massachusetts General Hospital in Cambridge, United States, has shown that in at least one case a disease-causing micro-organism uses many of the same virulence genes to infect humans and the primitive nematode worm.

His latest results suggest this may also be the case for the bug that produces salmonella poisoning and the "hospital bug" enterococcus.

"There's good reason to think that genetic analysis of these simple non-vertebrate hosts will lead to important, new information on bacterial pathogenesis. And while it will not eliminate animal research, it could significantly reduce the numbers involved," he said.

The principle has been demonstrated with Pseudomonas aeruginosa, a fatal "opportunistic" bug that is commonly found in hospitals, attacking patients whose immune systems have been damaged, such as those receiving chemotherapy, burns patients and sufferers of cystic fibrosis.

In studies, published in the Proceedings of the National Academy of Sciences and in Cell, Dr Ausubel found that this bacterium used some of the same genes to infect nematodes as humans, and even to cause a leaf-rotting disease in plants.

This suggests the bug targets basic cell machinery within all of the organisms that have not changed much through hundreds of millions of years of evolution.

The team told last week's meeting of the American Society of Microbiology in Los Angeles that they had subsequently found that salmonella, which had been believed to be especially adapted to thrive inside vertebrates such as humans and chickens, and enterococcus, a bug that is increasingly resistant to modern antibiotics, were quite capable of infecting and killing nematodes.

Preliminary results are suggesting that, as in the case of Pseudomonas aeruginosa, the same genes are used to infect both people and nematodes.

If this proves to be the case, it will herald a new way to tackle both infections.

Scientists could systematically test mutant strains of the bacteria on nematodes to find all of the genes the bacteria requires to infect a host. These could then be targeted for new drugs.

In addition, mutant strains of the nematodes could be tested to find which of the host's genes make it more susceptible or resistant to the bug.

Such experiments could be done on mice but the numbers required would be enormous, perhaps 40-50,000 in the case of salmonella.

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