[afro-nets] Cholera bacteria - new treatment and vaccine

[Leela McCullough <leela@healthnet.org>]

Advance in Cholera Bacteria Points to New Treatment and Vaccine
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http://dms.dartmouth.edu/news/2005_h2/07dec2005_taylor.shtml

08 Dec 2005

Opening a new door to an effective vaccine and therapy for a
disease that strikes thousands annually, researchers at Dart-
mouth Medical School discovered that the bacteria that causes
the intestinal disease Cholera spreads in the environment in
much the same way it infects humans. Appearing in the December 8
issue of the journal Nature, the study investigates the bacte-
rium Vibrio cholerae and its ability to attach to a host, ena-
bling it to multiply and adding to the risk of infecting humans.

"We've discovered, through genetics, a factor that is important
in the normal biology of the organism out in the environment and
it is also one of the very initial factors for cholera coloniza-
tion in the intestine," said Dr. Ronald Taylor, professor of mi-
crobiology and immunology at DMS who led the research. "Now that
we know what the bacterium attaches to in the intestine, we can
find ways to block that initial contact."

Cholera and the bacterium that causes it is found in contami-
nated drinking water and food, often in underdeveloped countries
and refugee camps. Once the disease takes hold, it causes diar-
rhea, vomiting, severe dehydration and can result in death if
treatment is not promptly given. In 2001 alone, 28 countries re-
ported over 40 outbreaks of cholera to the World Health Organi-
zation, resulting in the deaths of thousands.

Large outbreaks are often traced back to contaminated water sup-
plies that are commonly associated with algal or zooplankton
blooms. For the V. cholerae bacterium to infect someone with
cholera, the bacterium often binds to plankton in the aquatic
environment before it arrives at the human intestine via con-
taminated food and water sources. V. cholerae attaches to the
outer surface of plankton, made up of a carbonate substance
called chitin. Once attached to the plankton's chitin, the bac-
terium thrives on the carbon and multiplies. Humans do not have
chitin in the surface of intestinal cells, where the bacterium
takes hold, and researchers have been searching for another sub-
stance that could be responsible for playing a role in attach-
ment.

In the study, Taylor and colleagues screened cultured intestinal
cells and found mutant bacteria that had trouble binding to the
intestinal cells. One mutant strain of V. cholerae lacks a gene
that enables it to properly bind with a sugar called GlcNAc.
When they compared it with normal, wild-type V. cholerae bacte-
ria, the researchers found that the protein encoded by this gene
provided normal bacteria the ability to attach to the GlcNAc on
cells. The team verified that the GlcNAc in the intestine initi-
ates the attachment and colonization of the bacteria by testing
the mutant strain on zooplankton and cultured intestinal cells
in vitro as well as in an in vivo cholera model.

"We set out to find factors that would reduce the bacteria's
ability to bind to the epithelial lining of the intestine," said
Taylor. "What's interesting is that we've identified a factor
that works both in the environment and in the human body. This
type of link hasn't been discussed before and it has a strong
potential for vaccine and therapeutic development."

These findings could lead to a new form of therapy to treat peo-
ple with cholera. "Now that we know that the bacteria are bind-
ing this particular sugar, we could essentially trick the in-
fecting bacteria to bind to the sugar included in a derivative
of oral rehydration therapy solution instead of the intestine,"
said study co-author Brooke Jude, a fourth-year PhD student at
Dartmouth Medical School.

A vaccine for cholera already exists, but only works 50% of the
time and people who take it are only immune for 12 months, ac-
cording to Taylor. Taylor believes that a more effective vaccine
could be developed by inducing the production of antibodies di-
rected against the protein his research team has discovered,
thereby blocking its function. This would inhibit an early step
in the intestinal colonization process, and the bacteria would
pass harmlessly through the body. The authors acknowledge that
in addition to GlcNAc, there may be other points of attachment
that could still be responsible for allowing the bacteria to
bind to the intestine, and they are currently focusing their re-
search to identify any other areas of attachment..

"There may be more of these factors and as we find them and
knock them out, we'll decrease the ability for cholera bacteria
to colonize even further," said Taylor.

This study, "A colonization factor links Vibrio cholerae envi-
ronmental survival and human infection," was funded by the NIH
and a Rosalind Borison memorial fellowship.

Andrew Nordhoff
Dartmouth Medical School
mailto:andrew.nordhoff@dartmouth.edu
http://www.dartmouth.edu


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