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GENOME PROJECT FINDS THE TRIGGERS FOR E COLI ILLNESS
A team of more than two dozen scientists from the University of Wisconsin-Madison Genome Center announced the completed genome in the upcoming Jan. 25 issue of the journal Nature. The group discovered "islands of pathogenicity" across the genome that were picked up in entire clusters, possibly from other bacteria through the use of viruses. This ability for large-scale genetic change may make it harder to control the public health threat. This strain of E. coli O157:H7 causes an estimated 75,000 illnesses a year in the United States, including numerous deaths, and is especially dangerous to vulnerable populations such as children, the elderly and people with challenged immune systems. The food-borne pathogen was first identified in 1982 from an outbreak from contaminated hamburger, and reported cases have risen steadily. After completing the sequence of the O157:H7 strain, the researchers were able to compare that genome with E. coli K-12, a benign strain of bacteria sequenced in 1996 by Genome Center Director Fred Blattner. The team expected to find a few hot zones on which to concentrate, but instead found differences across the genome. "The sheer magnitude of the differences was totally shocking to us," says lead author Nicole Perna, an assistant professor of animal health and biomedical sciences. "We couldn't just zoom in on areas of difference between the two species. The changes were scattered throughout." The two strains of E. coli share about 3,500 common genes. But the O157:H7 strain had 1,300 additional genes that were not found in the harmless strain. The benign "cousin" bacteria also had 530 unique genes that were not shared with O157:H7. "This is a very 'plastic' genome, it changes quite rapidly," Perna says. "What this tells us is over a relatively short time on an evolutionary time scale, on the order of five million years, you get tremendous variation in the DNA of two similar organisms." Blattner, research team leader and senior author, says one of the paper's major findings is the suggestion of a large bank of genes that may be exchanged across an entire family of bacteria, including related organisms like Salmonella, Shigella, the Plague-causing organism Yersinia, and the plant pathogen Erwinia. Blattner labeled this phenomenon a "pathosphere," which blurs the genetic lines between species. "If the pathosphere is large enough, it could be an underlying factor in the emergence of new diseases," Blattner says. "We are already seeing this with the ability of some bacteria to develop antibiotic resistance. We need to be vigilant in finding the mechanisms that allow these pathogens to emerge." The study implicates viruses as a key transfer mechanism for introducing virulent genes into E. coli. Some viruses, called bacteriophages, specifically target bacteria, and can carry with them a large amount of genetic baggage, pieces of which can cause disease, Blattner says. There are currently no effective treatments for E. coli O157:H7, which causes a severe form of bloody diarrhea and can also release toxins that damage kidneys and cause renal failure. E. coli is found in the intestines of animals, including humans, and also exists in the field and in streams. The O157:H7, while rare, is probably the most dangerous to humans. Perna says the sequencing accomplishment gives scientists a tangible set of targets for future work on drug treatments or vaccines. Researchers must first better understand how these different clusters of genes are being transferred horizontally across different species. "One of the first things we can do is improve our detection and surveillance before it becomes a public health issue," she says. "We now have a far better distribution of genetic markers to help identify this in the field." James Kaper, a microbiologist at the University of Maryland School of Medicine and national expert on E. coli infections, says the paper will help in vaccine development and in creating new diagnostic tests. Preventive measures are extremely important with E coli O157:H7 because of its low infectious dosage and relative resistance to heat. "The species E. coli is remarkably versatile. It can be found normally in human intestines and is also capable of causing a variety of infections, from urinary tract infections to diarrhea to neonatal meningitis," Kaper says. "This paper will provide important insights into how a pathogen becomes a pathogen." This completed genome adds to a growing list of medically important microbes that have been fully sequenced, including tuberculosis, gonorrhea and cholera. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, says the national campaign will lead to better methods of diagnosing and treating an array of disease-causing pathogens. The project was funded by NIAID, an arm of the National Institutes of Health; the Department of Energy; the National Science Foundation; and a variety of foundations devoted to biomedical research. Other UW-Madison contributors include: Guy Plunkett and Val Burland, Genome Center scientists; genomics professors David Schwartz and Thomas Anantharaman; and medical microbiology and immunology professor Rodney Welch.
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