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Nicht mehr neu in der Wissenschaft, aber für die meisten Normalsterblichen wohl immer noch unbekannt:

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Date:         Mon, 12 Nov 2001 16:48:14 -0500
Reply-To: "NIH OLIB (OD)" <olib@OD.NIH.GOV>
Sender: "US Dept of HHS: Press Releases, Other Info"
              <HHSPRESS@LIST.NIH.GOV>



NATIONAL INSTITUTES OF HEALTH

National Institute of Allergy and Infectious Diseases

NIH NEWS RELEASE

EMBARGOED FOR RELEASE
Monday, November 12, 2001
5:00 p.m. EST

Contact:
Sam Perdue
(301) 402-1663
sp189u@nih.gov


HIDDEN TOXIN GENE IN "CHLAMYDIA" LINKED TO CHRONIC ILLNESSES

After more than 50 years of searching, scientists have
discovered a key gene that enables certain bacteria to
cause blindness and debilitating genital tract infections.
Using the recently completed genetic blueprint of the
bacterium "Chlamydia trachomatis", researchers from the
National Institute of Allergy and Infectious Diseases
(NIAID) have found a gene that encodes a cell-destroying
toxin.  Long suspected but never identified, the toxin
helps explain why only some chlamydial strains cause
chronic illness.  The discovery, described in the
"Proceedings of the National Academy of Sciences" November
13 online early edition, opens potential new avenues for
treating or preventing chlamydial diseases.  It also
highlights how DNA sequencing can help scientists identify
new ways to combat disabling or deadly infections.

Unlike most bacteria, "C. trachomatis" lives inside cells.
Chronic infections of the eyelids can scar the eyes and
lead to trachoma, the most common cause of preventable
blindness worldwide.  In the United States, "C.
trachomatis" infection is the most common sexually
transmitted disease (STD) and can lead to pelvic
inflammatory disease, tubal pregnancies and infertility in
women.  All of these diseases are caused by chronic
inflammation at the site of infection, but not all "C.
trachomatis" strains produce this effect.  Since the late
1940s, researchers have believed a toxin might cause the
inflammation, but no such toxin had ever been found.

"These bacteria cause debilitating illnesses in hundreds of
millions of people throughout the world," says Harlan
Caldwell, Ph.D., a leading chlamydia researcher at NIAID's
Rocky Mountain Laboratories in Hamilton, Mont.  "If we
could find a toxin that helps the bacteria attack and
destroy cells, we would have a major new target for
diagnostic tests, vaccines and drugs."

Dr. Caldwell joined Robert Belland, Ph.D., and their
colleagues to look for the toxin using a new tool: the
genetic blueprint of "C. trachomatis".  The researchers
compared the genomes of two "C. trachomatis" strains: one
that is restricted to mucosal surfaces and infects the eyes
and genital tract, and one that is invasive and infects
cells in the lymph nodes.  The genes of the two strains
were almost identical except for a single region of the
bacterial chromosome.  When the investigators studied that
region in more detail, they found a stretch of DNA that
resembled a known gene for the so-called toxin B of
"Clostridium difficile".  That bacterium causes a
potentially fatal infection of the large intestine in
humans and is closely related to the deadly microbes that
cause tetanus, botulism and gangrene.  Toxin B makes the
protein scaffolding inside of cells collapse, causing the
cells that line mucosal passageways to separate from one
another.  The "C. difficile" bacteria can then use the
spaces between the cells to invade deeper into the
intestinal wall.

To see if the candidate gene found in "C. trachomatis"
actually encoded a protein similar to clostridial toxin B,
Drs. Caldwell and Belland looked for evidence of the toxin
in the bacteria.  Their studies showed that "C.
trachomatis" produces specific changes in infected cells,
and those changes are indistinguishable from ones induced
by the clostridial toxin.  Infected cells also contained
toxin-encoding RNA, a type of DNA photocopy that shuttles
its genetic instructions to the cell's protein-making
machinery.  The researchers also showed that infected cells
contain a protein resembling toxin B, suggesting the cells
deciphered the RNA's instructions.

"Finding the toxin would have been nearly impossible
without the genome information," says Dr. Belland.  Without
it, he explains, the search would have resembled the
proverbial needle in a haystack.  The genome gave them a
good idea of what haystack the needle was in, where it was
located, and what the needle might look like.

Anthony S. Fauci, M.D., director of NIAID, agrees that
genome sequencing offers great promise in improving global
health.  "Determining the DNA sequence of the world's
leading infectious microbes is a high priority within
NIAID," he states.  "This study is one example of how that
commitment can provide researchers with a powerful tool for
understanding and eventually treating or preventing
infectious diseases."

The discovery of a specific toxin associated with trachoma-
and STD-causing "C. trachomatis" strains is a boon to
investigators trying to understand these diseases.  Drs.
Caldwell and Belland plan to continue their studies to
determine how the toxin helps the bacteria cause disease
and how it interacts with a person's immune system.
Further investigations should reveal new ways to attack the
bacteria, perhaps by using an antitoxin vaccine, as is done
with tetanus and diphtheria, or by developing drugs that
block the toxin's ability to destroy cells.

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.
------------------------------------

REFERENCE:
RJ Belland, et al. "Chlamydia trachomatis" cytotoxicity
associated with complete and partial toxin genes.
"Proceedings of the National Academy of Sciences" Early
Edition online (Nov. 13, 2001).

Copies of the article are now available to reporters from
the PNAS news office, tel. (202) 334-2138, or e-mail
pnasnews@nas.edu.

Press releases, fact sheets and other NIAID-related
materials are available on the NIAID Web site at
http://www.niaid.nih.gov.

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