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5 December 2013 11:26 am ,
Vol. 342 ,
At age 30, Dutch biologist Freek Vonk has built up a respectable career as a snake scientist. But in his home country,...
Since arriving on the island of Guam in the 1940s, the brown tree snake ( Boiga irregularis ) has extirpated native...
An animal rights group known as the Nonhuman Rights Project filed lawsuits in three New York courts this week in an...
Researchers have been hot on the trail of the elusive Denisovans, a type of ancient human known only by their DNA and...
Thousands of scientists in the Russian Academy of Sciences (RAS) are about to lose their jobs as a result of the...
Dyslexia, a learning disability that hinders reading, hasn't been associated with deficits in vision, hearing, or...
Exotic, elusive, and dangerous, snakes have fascinated humankind for millennia. They can be hard to find, yet their...
Researchers have sequenced and analyzed the first two snake genomes, which represent two evolutionary extremes. The...
- 5 December 2013 11:26 am , Vol. 342 , #6163
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Gene Promises Route to Potent Vaccines
6 May 1999 8:00 pm
Scientists have found a remarkable gene that may lead to a whole new generation of vaccines and antibiotics. In this week's issue of Science, researchers describe a gene in Salmonella bacteria that, like a master switch, turns on a range of other genes needed for infection. Bacteria stripped of the gene are harmless to mice but make an excellent vaccine.
Pathogens have many so-called "virulence genes," which are switched off when the bacteria are living on a petri dish or a chicken in the refrigerator, but spring into action once they enter the gut of a mammal. A team led by geneticist Michael Mahan at the University of California, Santa Barbara, had already discovered some 250 of these genes in Salmonella typhimurium, which causes food poisoning in humans and a typhoidlike disease in mice.
In search of a single gene that could turn many virulence genes on and off, the researchers turned their attention to DNA adenine methylase (Dam), an enzyme that plays a role in DNA repair and is known to be necessary for infection in Escherichia coli strains that cause urinary tract infections. To see whether Dam might play a wider role, the team created an S. typhimurium strain that lacked the dam gene. When given orally to mice, the bacteria proved utterly innocuous: They entered the gut lining but didn't cause a major infection. Measurements of gene activity showed that the absence of Dam had altered the expression of at least 20 virulence genes.
Drugs that block Dam could slow bacterial growth and possibly offer a whole new generation of antibiotics, says Mahan. Also exciting is the possible use of Dam-stripped bacteria as a vaccine. When the team immunized 17 mice with Dam-negative S. typhimurium, the animals were immune to the normal bacterium 5 weeks later; they could withstand doses of up to 10,000 times the amount that killed nonimmunized mice.
The findings could lead to animal vaccines that help eradicate Salmonella from the food chain. Other diseases could also become targets. Because genetic studies have shown that the bacteria that cause cholera, meningitis, plague, dysentery, and syphilis all have dam, perhaps they too can be crippled by knocking out the dam gene. "On the heels of this paper, a variety of labs will probably quickly knock out [dam] in their individual bugs," predicts microbiologist John Mekalanos of Harvard Medical School in Boston.