- News Home
17 April 2014 12:48 pm ,
Vol. 344 ,
Officials last week revealed that the U.S. contribution to ITER could cost $3.9 billion by 2034—roughly four times the...
An experimental hepatitis B drug that looked safe in animal trials tragically killed five of 15 patients in 1993. Now,...
Using the two high-quality genomes that exist for Neandertals and Denisovans, researchers find clues to gene activity...
A new report from the Intergovernmental Panel on Climate Change (IPCC) concludes that humanity has done little to slow...
Astronomers have discovered an Earth-sized planet in the habitable zone of a red dwarf—a star cooler than the sun—500...
Three years ago, Jennifer Francis of Rutgers University proposed that a warming Arctic was altering the behavior of the...
- 17 April 2014 12:48 pm , Vol. 344 , #6181
- About Us
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.