May 20, 2002
Researchers shed light on bacterial infection linked to ulcers and stomach
By Linley Erin Hall
About 40 percent of the U.S. population is infected with a bacterium that can cause
stomach inflammation and ulcers and increases the risk of stomach cancer. Although
the bacterium, called Helicobacter pylori, was discovered in the 1980s, scientists
are just now beginning to understand how it causes infections in the stomach lining.
Karen Ottemann, assistant professor of environmental toxicology, is studying H.
pylori's ability to move around and the role this motility plays in infections.
Her latest findings, published in the April issue of the journal Infection and
Immunity, indicate that for H. pylori to start and maintain an infection,
it needs to be able to swim.
|H. pylori moves around using long protein "tails" called flagella.
"It's surprising that motility is used both to start the infection and probably
to keep it going," Ottemann said.
Ottemann uses H. pylori as a model to understand the role of motility in host-parasite
interactions generally. The molecular machinery involved in movement represents a
potential target for new antibiotics, but no one really knows how bacteria use motility
to infect humans and other mammals, she said.
Bacteria such as H. pylori move around in their animal hosts, but why they
move, whether toward food, away from the host's immune cells, or toward or away from
other molecules, is still an open question. H. pylori does not grow in the
highly acidic stomach environment, so it may need to move quickly to the less acidic
mucus layer that coats the stomach lining to achieve infection. Being able to swim
in the mucus layer may also thwart the body's defense systems so that the bacterium
causes a more persistent infection.
Infection with H. pylori usually occurs in early childhood, but symptoms do
not become apparent until adulthood, if ever. Researchers believe that the bacteria
are transmitted by ingestion of contaminated food or water or oral contact with an
infected person. The infection process remains poorly understood, but Ottemann's
research on the role of motility is shedding light on this mystery.
H. pylori moves around using long protein "tails" called flagella.
Other researchers showed previously that H. pylori without flagella caused
mild infections in mice. Ottemann and graduate student Andrew Lowenthal examined
whether lack of motility or some other consequence of the lack of flagella reduced
the bacteria's potency.
Ottemann and Lowenthal introduced mutations into the gene for a protein essential
to H. pylori movement, so that the bacteria possessed flagella but could not
move. The researchers then compared the mutant bacteria's ability to infect mice
with that of normal H. pylori. Some mice exposed to the nonmotile bacterium
did not become infected at all, and the ones that did contained fewer bacteria than
mice infected with normal H. pylori. Furthermore, much higher doses of the
mutant bacteria were required to establish an infection at all--more than one million
mutants compared to only 150 normal bacteria. Thus, the bacteria need to be able
to swim in order to start and maintain an infection, Ottemann said.
In the next phase of her research, Ottemann will create H. pylori in which
the genes that produce proteins necessary for motility can be turned off after an
infection has started. She hopes to show that by shutting down these genes she can
halt an already established infection. If true, a compound that stops H. pylori
from swimming could be a powerful drug.
Many people treat H. pylori-induced stomach inflammation with over-the-counter
acid reducers until a painful ulcer sends them to a physician. After a breath test
or stomach biopsy confirms H. pylori infection, the bacteria are usually wiped
out by a course of antibiotics. But antibiotic-resistant strains of the bacterium
Many other bacteria, including Campylobacter jejuni, the leading cause of
diarrhea in the United States, also use flagella to move around. Ottemann's work
on motility may be laying the foundation for a whole new class of antibiotics, and
is shedding new light on host-parasite interactions.
"It's amazing how hosts and parasites interact," Ottemann said. "A
tiny organism can mess up a large, complex one so easily."
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