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Friday, May 7, 1999 Published at 12:05 GMT 13:05 UK


'Switching off' disease

"Disarmed" bacteria provoked a strong immune response

Scientists in the US may have found a new way to combat bacterial infection in the fight against diseases that kill millions worldwide.

BBC Science Correspondent Christine McGourty: Will it work in humans?
It might even provide an alternative to antibiotics which are becoming less effective as bacteria develop resistance to our most successful drugs.

The scientists from the University of California in Santa Barbara (UCSB) say they have identified a "master switch" that controls the genes in microbes which make them infectious.

Their studies focused on Salmonella typhimurium, a bug that causes severe stomach upsets and even death. By manipulating a special enzyme, the researchers were able to "turn off" the danger genes, in effect "disarming" the bacterium.

But the microbe, although incapable of spreading disease, still provoked a strong immune response that was highly effective against subsequent infections, making it an ideal live vaccine.

Immunised mice survived

The enzyme is called DNA adenine methylase, or Dam for short. It is essential for the development of Salmonella-related illness because it regulates the expression of at least 20 genes necessary for infection.

[ image: Knocking out the Dam gene stops infection]
Knocking out the Dam gene stops infection
The UCSB team's experiments, reported in the journal Science, show that Salmonella bacteria containing a mutated, or altered, form of Dam fail to produce the proteins that would normally make the bugs virulent.

They injected 17 mice with the Dam-mutant bacteria and then challenged them with high doses of Salmonella typhimurium. All 17 mice survived the challenge while an unimmunised control group of mice all died.

When they took a closer look, the researchers found that the "disarmed" bacteria grew in the mucus lining the intestines but could no longer invade or colonise other areas of the gut.

"The bacteria are completely disabled in their ability to cause disease, and these crippled bacteria work as a vaccine since they stimulate immune defences against subsequent infections," says Professor Michael Mahan, one of four scientists in the Santa Barbara team.

Drug-resistant pathogens

Significantly, the Dam "master switch" is not confined to salmonella - it exists in many other infectious bacteria, including those which cause cholera, plague, typhoid, dysentery, meningitis and E.coli poisoning.

[ image: Professor Michael Mahan:  A major aid in the fight against disease]
Professor Michael Mahan: A major aid in the fight against disease
Currently, microbial infections are the leading killer worldwide, responsible for 17 million deaths each year. The researchers believe their discovery will be a major aid in the fight against newly emerging, drug-resistant pathogens.

"When it comes to bacterial disease, the wake-up call has been sounded," says Professor Mahan. "Our microbial defences are crumbling as superior pathogens have emerged that can no longer be controlled by available antibiotics.

"There are numerous warning signs including the recent emergence of drug resistant tuberculosis, Staphylococcus, and Streptococcus."

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