The just completed genome sequence of a deadly type of
"Escherichia coli" bacteria suggests that the microbe
frequently picks up new DNA from other bacteria and
bacterial viruses, including genes that may help explain
why this organism is exceptionally virulent and sometimes
difficult to treat. The results of this sequencing project,
supported by the National Institute of Allergy and
Infectious Diseases (NIAID), are reported in the January 25 issue of "Nature".
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 US 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 important pathogen."
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
"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 organisms.
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 problem."
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.