such as "Introduction", "Conclusion"..etc
CHAPEL HILL – Bacteria can swim, propelling themselves through
fluids using a whip-like extension called a flaggella. They can also
walk, strolling along solid surfaces using little fibrous legs called
pili. It is this motility that enable some pathogenic bacteria to
establish the infections – such as meningitis – that cause their human
hosts to get sick or even die.
Now researchers at the
University of North Carolina at Chapel Hill have discovered that a
single atom – a calcium, in fact – can control how bacteria walk. By
resolving the structure of a protein involved in the movement of the
opportunitistic human pathogen Pseudomonas aeruginosa, the scientists
identified a spot on the bacteria, that when blocked, can stop it in
its tracks. The finding identifies a key step in the process by which
bacteria infect their hosts, and could one day lead to new drug targets
to prevent infection.
"When it comes down to it, a single atom
makes all the difference," said senior study author Matthew R. Redinbo,
Ph.D., professor of chemistry, biochemistry and biophysics at UNC. His
findings appear in the Dec. 28, 2009, early online edition of the Proceedings of the National Academy of Sciences.
the last few years, Redinbo and his team has been working in close
collaboration with Matthew C. Wolfgang, Ph.D., an assistant professor
of microbiology and immunology and a member of the Cystic
Fibrosis/Pulmonary Research and Treatment Center at UNC, trying to
figure out how bacteria's tiny legs or pili function. The researchers
began to look at one of the many types of pili, called type IV pili.
Type IV pili are basically long, dense fibers that bacteria assemble
(extension) or disassemble (retraction) quite quickly.
pili act as grappling hooks – the bacteria extend the fibers out, the
fibers attach or stick to a surface, and then retracted back into the
bacteria, pulling it along," said Wolfgang. "This crawling movement is
called twitching motility, and without it Pseudomonas, a common cause
of hospital-acquired pneumonia would never be able to move from the
lung tissue into the bloodstream, where the infection becomes lethal."
researchers knew that inside the cell lie the tiny little motors –
called ATPases – that drive the extension and retraction of the pili.
One of these ATPases is the extension motor, which sticks the
bacteria's leg out. The other ATPase is the retraction motor, which
pulls it back in. But what wasn't clear was how the two motors were
coordinated so that pushing and pulling didn't occur at the same time.
That is what Redinbo and Wolfgang set out to discover.
they resolved the crystal structure of the Pseudomonas PilY1 protein,
which other research had shown was necessary for the creation of pili.
They made large amounts of the protein, coaxed it out of solution so
that it formed a crystal, and then put the crystal under intense x-ray
beams through a process called x-ray diffraction that resulted in a
series of spots. Based on the spots, the researchers calculated what
the protein looked like. When they studied the structure, one
particular site – the binding site of a calcium atom – looked like it
could be important for the function of the protein. So the researchers
began to tinker with the site, looking to see if the changes they made
affected the protein's behavior.
When they changed the protein
so it could no longer bind calcium, the bacteria couldn't make any
legs. When they fooled the protein into thinking it was forever bound
to calcium, the bacteria made legs but couldn't retract them,
essentially becoming paralyzed. The results suggested that the protein
has to bind calcium to make legs, but it also has to be able to let go
of the calcium to pull the legs back in.
"We found it pretty
remarkable that the binding of a single atom to a protein that is
outside the cell is sufficient to tell these motors that are inside the
cell to either stop pushing or stop pulling," said Redinbo. He says
they are currently using a combination of genetics and biochemistry to
figure out how this long-distance communication is possible.
University of North Carolina School of Medicine
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