Researchers Uncover Key To Survival Of Bacterium That Causes Lyme Disease 2004



Researchers Uncover Key To Survival Of Bacterium That Causes Lyme
Disease

University Of Texas Southwestern Medical Center At Dallas

February 24, 2004

A specific outer-surface protein found in the bacterium that causes
tick-borne Lyme disease is essential to survival of the bacterium in
its natural life cycle and colonization in the insect, researchers at
UT Southwestern Medical Center at Dallas have found.

A study published online today in The Journal of Experimental Medicine
provides the first proof of a long-held theory that outer surface
lipoprotein A (OspA) must be present for Borrelia burgdorferi (Bb) --
the bacterium that causes Lyme disease -- to colonize in ticks.

"This OspA molecule has been intensively studied for the last 20 years,
but nobody really knew what it did," said Dr. Michael Norgard, chairman
of microbiology at UT Southwestern and the paper's senior author. "Now
we know that it's needed for the organism to colonize and replicate in
the midgut of the tick. If the bacterium doesn't have this molecule, it
can't sustain itself there."

Lyme disease, discovered in 1977, is the most prevalent tick-borne
infection in the United States. The bacterium that causes the disease
is transmitted to humans by the bite of infected deer ticks. In 2002
more than 23,000 cases of Lyme disease were reported to the Centers for
Disease Control and Prevention, with 95 percent of the cases located in
the northern and northeastern portions of the country.

Symptoms include fever, malaise, fatigue, headache, muscle and joint
aches, and a characteristic "bull's-eye" rash that surrounds the site
of infection.

Dr. Xiaofeng Yang, assistant professor of microbiology at UT
Southwestern and lead author of the journal article, created a mutant
of an infectious human strain of the Bb bacterium by inactivating, or
"knocking out," a DNA fragment encoding OspA. He then injected the
mutant strain into ticks and mice and found that, while it was not
required for infection of mice, it was crucial for colonization of the
ticks.

After observing the difference between the bacterium containing OspA
and the mutant, Dr. Yang introduced a wild-type OspA gene back into the
mutant strain, and colonization of the bacterium was restored.

The first agent of Lyme disease was discovered in ticks 23 years ago,
but the molecular basis of how the bacterium thrives in nature through
a complex life cycle involving ticks and mammals has not been
understood. This research is an important step toward unraveling that
mystery, Dr. Norgard said.

"The medical implications are not yet clear, but it adds an important
piece to the puzzle," Dr. Norgard said. "One of the real technical
advances here is in genetics, because so many other investigators have
tried to inactivate this gene unsuccessfully."

Dr. Thomas Templeton of the Department of Microbiology and Immunology
at Weill Medical College of Cornell University, commented on the
significance of the findings in an editorial that will be published
with the paper in the March 1 print edition of the journal.

"These results greatly solidify a body of experimentation implicating
OspA and OspB as midgut stage antigens ... but more importantly set the
stage for dissection of OspA/OspB function," Dr. Templeton wrote.

Sophie Alani, a research assistant in microbiology at UT Southwestern,
and researchers from Yale University School of Medicine, also
collaborated on the study.

The research was funded by the National Institute of Allergy and
Infectious Diseases.

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