Contact: Jeffrey Minerd
The type of foodborne E. coli that was sequenced, designated O157:H7, is a
worldwide threat to public health and has triggered scores of recent
outbreaks of hemorrhagic colitis (painful, bloody diarrhea) and many
fatalities from kidney failure, according to project leaders at the Genome
Center of the University of Wisconsin-Madison (UW-Madison). Close to 75,000
infections caused by O157:H7 transmitted through contaminated food occur
annually in the United States, and such infections are most dangerous to
children under the age of 10 and the elderly. One well-known U.S. outbreak
in 1982, linked to contaminated hamburger meat, led to identification of
O157:H7. An outbreak last summer in Milwaukee, Wisconsin, resulted in 60
cases and the death of a 3-year-old child.
"E. coli O157:H7 is one of the most dangerous pathogens threatening our food
and water supplies," says Anthony S. Fauci, M.D., director of NIAID.
"Better ways to diagnose, treat and prevent E. coli O157:H7 infections are
badly needed. This new information will provide important leads to
scientists working to reduce the human and economic burdens of this
When researchers compared the more than 5,000 genes of this harmful E. coli
to those of a previously sequenced and harmless laboratory strain, they
found O157:H7 possessed more than 1,000 genes the other strain lacked. Many
of these new genes appear to have been transferred from other bacteria by
way of bacterial viruses, indicating that over evolutionary time E. coli
acquires foreign genes at a much higher rate than other organisms.
"We found a whole host of unexpected differences between the two types of E.
coli," says lead author Nicole T. Perna, Ph.D., of UW-Madison, "things that
have never been seen before, and things we hadn't thought to look for." The
genetic variability of E. coli and its close relatives may help explain the
diversity of human diseases they cause.
"This bacterium is loaded with interesting genes," says UW-Madison research
team leader Frederick R. Blattner, Ph.D. E. coli can obtain new genes in
several ways, he explains, but the new research especially points the finger
at viruses called bacteriophages that infect only bacteria. Bacteriophages
insert their genetic material into bacterial DNA. Some of these viral
genes, originally acquired from other bacteria in E. coli's environment, may
prove advantageous. The new genes can quickly spread through an E. coli
population through a process called conjugation, whereby bacteria exchange
DNA directly. "We have found that the genomic pieces are constantly
shuffling around so that any particular strain contains a subset of the full
range available," Dr. Blattner says. "We've termed this larger pool of
available genes the pathosphere."
Some of the new genes may contribute to the organism's virulence. E. coli
produces two known toxins called Shiga toxins, which can cause fatal kidney
damage. But initial analysis of the genome sequence shows that several new
genes, probably inserted by viruses, are likely toxin-making genes as well.
These genes appear similar to known toxin genes in other pathogenic
The new genes also help explain why E. coli O157:H7 infections are sometimes
difficult to treat, says Guy Plunkett III, Ph.D., a geneticist at
UW-Madison. The reason is that certain antibiotics used against E. coli can
actually stimulate virally infected bacteria to produce more viruses and
viral toxins. "The antibiotics kill the E. coli, but in their death throes
the bacteria release more of these toxins," Dr. Plunkett explains. "So in
the course of treating the disease, you could actually exacerbate the
Another set of newly discovered E. coli genes might allow the bacteria to
withstand fever, one of the body's defenses against infection, Dr. Plunkett
says. Even so, nothing protects the microbe against the higher temperatures
of thorough cooking.
The genome sequencing has done more than reveal how tough this organism is,
however. The sequencing has given scientists a much larger number of
genetic markers segments of DNA that can be used to identify the bacteria
than were previously known, Dr. Perna points out. This information
should allow scientists to detect the presence of E. coli more easily,
whether it is in humans or potentially contaminated food.
In addition, the new genetic information should aid efforts to create an
animal vaccine against this pathogen, says Dennis Lang, Ph.D., enteric
diseases program officer at NIAID. Such a vaccine might reduce or eliminate
E. coli in cattle or other animals, thus limiting subsequent human exposure,
Dr. Lang explains. A human vaccine would be less useful but could help
prevent person-to-person spread during large foodborne outbreaks, Dr. Lang
The researchers used a new technique called optical mapping, invented by
co-author David C. Schwartz, Ph.D., also of the UW-Madison Genome Center, to
help organize this E. coli gene sequence. With optical mapping, scientists
use a fluorescence microscope to photograph and measure a specially prepared
DNA molecule, allowing them to more quickly determine its size and
structure. The National Human Genome Research Institute (NHGRI) provided
funds to develop the optical mapping methods.
NIAID is a component of the National Institutes of Health (NIH). NIAID
supports basic and applied research to prevent, diagnose, and treat
infectious and immune-mediated illnesses, including HIV/AIDS and other
sexually transmitted diseases, tuberculosis, malaria, autoimmune disorders,
asthma and allergies.
NHGRI supports the NIH component of the Human Genome Project, a worldwide
research effort designed to analyze the structure of human DNA and determine
the location of the estimated 100,000 human genes. The NHGRI Intramural
Research Program develops and implements technology for understanding,
diagnosing and treating genetic diseases.
Press releases, fact sheets and other NIAID-related materials are available
on the NIAID Web site at www.niaid.nih.gov.