E. coli vaccine one step closer
Memphis investigators see promising results in lab tests on
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a basement laboratory in the Memphis
medical center comes new hope for a vaccine to protect against a strain of
the E. coli bacteria that kills thousands of youngsters every year and sidelines
millions of travelers.
a recent online edition of the scientific journal Nature, investigators from
the Memphis Veterans Medical
Center and the
University of Tennessee Health Science Center described promising early
results for two experimental vaccines. Both were largely effective at
preventing E. coli from gaining a foothold in the digestive tracts of mice.
"There is still a tremendous amount of work to be done" to create a
human vaccine, cautioned Dr. James Fleckenstein, the study's senior author.
vaccines were designed to block the infection by preventing a protein at the
end of the E. coli's whip-like flagella from
attaching to a second protein, known as EtpA. EtpA is secreted by the E. coli bacteria and apparently
plays a role in helping the bug stick to the intestinal tract of the
unsuspecting patient. The interaction between the two proteins is a key step
in the infection process.
called the discovery of the protein interaction the most promising vaccine
target in his nearly 20 years of research. Fleckenstein is a UT Health
Science Center associate professor of medicine and molecular sciences. He is
also an investigator at the Memphis
does look like a very promising lead," said Dr. George Munson, of the University of Miami's Miller School of Medicine.
Munson, an assistant professor of microbiology and immunology, wasn't part of
research described in the recent publication.
global push to develop a vaccine to protect against this E. coli infection
began years ago. But Munson said Fleckenstein's group has identified two new
targets. "It applies possible new routes to a safe and effective
vaccine," he explained.
which Fleckenstein's laboratory identified in 2006, also apparently plays a
role in other diarrheal diseases, Fleckenstein said. That raises hope any
potential vaccines targeting EtpA will prove useful
against other infections.
publication comes amid heightened interest in combating this strain of E.
coli. While various strains of the bug live harmlessly or even helpfully in
the human gut, Fleckenstein's work focuses on one of the bad actors.
is formally known as enterotoxigenic Escherichia
coli, or ETEC. Found most commonly in developing countries where drinking
water is contaminated by fecal material, ETEC is a major cause of traveler's
diarrhea. It is also blamed for roughly 500,000 deaths annually, primarily
due to dehydration among patients age 5 and younger.
we had clean water in developing countries, we wouldn't have a need for a
vaccine," Fleckenstein said. He said U.S. outbreaks of the infection
are also increasing, likely due in part to an increasingly global food
2008, the Bill & Melinda Gates Foundation earmarked $50 million to
support development of vaccines against ETEC and another bacteria
linked to deadly diarrhea in youngsters.
is also among the bacteria whose genetic blueprints are being deciphered. Of
the dozens of different versions of ETEC, Fleckenstein said three have been
decoded. Such detailed genetic information will likely identify additional
vaccine targets, he said.
played a role in the Memphis
group's latest advance.
laboratory had been trying without success to purifying EtpA.
EtpA is a sticky protein that helps E. coli adhere
to the small intestines and begin to spread. Fleckenstein's laboratory
discovered EtpA in 2006. "It acts as a molecular glue," he said.
eventually sent samples to the laboratory of Dr. George M. Hilliard at UT
Health Science Center. His analysis showed EtpA was
bound with flagellin, a small protein at the tip of
ETEC's flagella. Memphis investigators now believe that
binding plays a key role in E. coli infections.
Fleckenstein's group used both EtpA and flagellin as the basis of three different experimental
said experimental vaccines that tapped the flagella proteins triggered the
strongest immune response in animals. But he said additional work is needed
before they are ready for human trials.
are trying to tease out the parts of the flagella that will stimulate an
immune response without causing problems" for humans, he said.
Investigators are also wary of causing problems by inadvertently killing off
helpful E. coli strains.
By The Numbers
or enterotoxigenic Escherichia coli, is a bacterial
infection spread primarily through unclean drinking water.
is blamed for about 500,000 deaths annually. The victims are usually infants
and toddlers living in developing countries.
bug also causes millions of cases of traveler's diarrhea annually.