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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 are reported in the January 25 issue of
Nature.
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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.
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"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."
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| 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. |
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"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. |
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"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." |
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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.
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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. |
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"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." |
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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. |
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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.
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| In addition, the new genetic information should aid efforts to create an
animal vaccine against this pathogen. 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 says.
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| The researchers used a new technique called optical mapping, invented by
co-author David C. Schwartz,Pn.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.
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