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Discovery of key process in bacterial infection could lead to new drug targets to prevent infection

Published on January 4, 2010 at 11:34 PM · No Comments

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.

For 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.

"These 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."

The 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.

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