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Scientists flip germs' 'master switch' Salmonella discovery offers hope of
vaccines

Saturday, May 8, 1999: Washington - Researchers say they have developed a
potential vaccine against salmonella bacteria, which cause a range of
deadly diseases from food poisoning to typhoid.

They think their vaccine, tested so far only in mice, may work against
several varieties of the bacteria.

They also say it takes advantage of an enzyme found in many bacteria,
including those that cause cholera, plague and meningitis. This could form
the basis not only of new vaccines but of new antibiotics against bugs that
are quickly becoming resistant to current drugs.

"This vaccine is based on a master switch that affects the activation of
many things," Mike Mahan of the University of California Santa Barbara, who
helped lead the study, said in a telephone interview on Thursday.

The "master switch," they reported in the journal Science, is a gene called
DAM, for DNA adenine methylase. It regulates at least 20 other genes that
bacteria use to infect their victims.

By working with Salmonella typhimurium, which kills mice, Mr. Mahan and his
colleagues first determined that DAM is needed for infection. They created
a mutant form of the bacteria in which DAM was faulty. Then they immunized
17 mice with the mutant and infected them with the salmonella. All the mice
lived. A second group of unimmunized mice all died of the salmonella.

The scientists killed and examined the immunized mice and found the
salmonella bacteria were growing in their intestines but had lost their
ability to spread elsewhere and wreak havoc.

In addition, they tested immunized mice with another strain of salmonella.
The mice were protected against that strain as well.

"This DAM gene is in basically every enteric pathogen," Mr. Mahan said,
referring to germs that cause digestive disease. "It's in cholera, the bugs
that cause dysentery."

It is also in Yersinia pestis, the cause of plague, Hemophilus influenzae,
which causes a range of ills from ear infections to meningitis, and
Treponema pallidum, the syphilis germ.

One next step is to see whether DAM acts as such a master switch in those
other microbes, said David Low, who also worked on the study.

Reuters News Agency

janet paterson
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