Genomes for Two Salmonella Strains Sequenced

Studies reveal blueprint for typhoid and food poisoning bacteria

THURSDAY, Oct. 25, 2001 (HealthDayNews) -- Two international teams of researchers have finished mapping the genetic sequences of two major strains of Salmonella enterica. One causes typhoid, and the other causes food poisoning.

The researchers published the genomes of the subtypes Salmonella typhi and Salmonella typhimurium in today's issue of Nature,.

S. typhi, causes typhoid, a potentially lethal disease that causes high fever, nausea and vomiting. The disease has been essentially eliminated in developed countries, but still causes roughly 16 million cases and 600,000 deaths every year elsewhere.

Led by Julian Parkhill at the Sanger Centre in Cambridge, England, researchers showed that the DNA for S. typhi, a strain that is resistant to multiple antibiotics, contains more than 4.8 million base pairs, like rungs on a ladder, and that hundreds of those pairs are shared with the genome of Escherichia coli, a bacteria commonly found in the guts of mammals.

The researchers also found that S. typhi has genes similar to those of Yersinia pestis, better known as the plague.

Typhoid infects only humans, limiting the kinds of scientific experiments that can be done.

The second newly sequenced strain, S. typhimurium, can affect other organisms, including causing a typhoid-like disease in mice. Michael McClelland, lead researcher of the second project, says the sequence shows about a 10 percent to 15 percent difference between the genomes of S. typhimurium and S. typhi.

S. typhimurium causes an estimated 1.4 million cases of stomach upset in the United States every year, including about 1,000 deaths. McClelland says the bacterium probably causes a 100 million cases and hundreds of thousands of deaths in developing countries.

"We found about 20 genes that we think are similar to genes that are already known to be involved in pathogenesis [causing disease]," says McClelland, director of the molecular biology program at the Sidney Kimmel Cancer Center, in San Diego, Calif.

"We were able to identify about 50 genes where we think the proteins for those genes end up on the surface of the cell. We think that these will be good targets for therapeutics or vaccines because they're exposed."

The researchers also determined when specific genes in the bacterium arose during the germ's evolution and that S. typhimurium and E. coli have a common ancestor.

Stanley Maloy, professor of microbiology and a salmonella expert at the University of Illinois at Urbana-Champaign, says S. typhimurium is a major killer in areas of the world where diseases like AIDS have left people with weakened immune systems.

"The sequence of S. typhimurium is likely to uncover some new genes that may play an important role in causing disease and therefore might be a good target for developing an antibiotic or developing a new, better vaccine," says Maloy.

The antibiotic resistance of the typhoid strain studied by Parkhill's team may have resulted from genes "jumping" between the bacterium and other pathogens, a process known as lateral transfer, the researchers say.

"It makes it into a very insidious, nasty bug that's hard to treat," says Maloy. "The sequence in that case may identify genes that would be good targets for developing better and improved treatments."

McClelland says typhoid's cousin, S. typhimurium, may be a source of some of that resistance. "Although our sequence does not have any of those antibiotic resistances because it's a laboratory strain, typhimurium may be a major source of antibiotic resistance for other bacteria that infect humans."

He points to research that suggests that antibiotics fed to livestock may be triggering resistance in S. typhimurium in animals, which is then transferred to S. typhi bacteria that cause disease in humans.

Maloy says researchers are just beginning to understand how lateral transfer occurs. "Comparison of the salmonella genomes is going to give us a wonderful insight into what's going on," he says.

McClelland says the findings also could prove useful to laboratories investigating whether S. typhimurium can be a used in cancer therapy. Weakened versions of the bug appear to concentrate in solid tumors, including breast and colon cancers, making them an ideal way to carry cancer-killing therapies to the tumor site.

What To Do

Maloy says while anthrax has captured recent headlines, S. typhimurium was the first organism used as a bioterrorist weapon in the United States. In 1984, the religious followers of Bhagwan Shree Rajneesh tried to influence the outcome of an election by putting S. typhimurium in a salad bar in The Dalles, Oregon. The attack sickened 751 people who ate or worked at the salad bar.

The Secret Service announced today that vials of salmonella were mailed to the Harlem office of former President Bill Clinton. The strain was not announced, and no one has been sickened.

For more information about salmonella, check Salmonella.Org.

The Centers for Disease Control and Prevention publishes fact sheets on typhoid fever and Salmonella enteriditis infection.

SOURCES: Interviews with Michael McClelland, Ph.D., professor and director, molecular biology program, Sidney Kimmel Cancer Center, San Diego, and Stanley R. Maloy, Ph.D., professor, of microbiology and director, Biotechnology Center, University of Illinois, Urbana-Champaign; Oct. 25, 2001, Nature
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