"Bacterial adhesion has been described for a century bacteria need to adhere in order to colonize," Sokurenko says. "It's taken a century before we've been able to understand what happens once you see the bacteria clump red blood cells. What happens is that the bacteria and blood cells start to separate after you stop shaking. Then, if you shake them again, they clump again. The moment shear starts pushing them away from the surface, the bacteria adhere tightly. It demonstrates an amazing flexibility by infectious bacteria and provides a mechanism for bacteria to resist the effects of free-flowing inhibitor molecules that can block the adhesion."
In other words, E. coli appears designed to colonize parts of the body that are exposed to a lot of shear force. It has hair-like protrusions, fimbriae, (with the FimH protein on their tips) that touch the nearby surface, detect the dragging force, and set off a chain of molecular events that cause it to cling more effectively.
The computationally derived insights of how the switch works were tested by using genetic approaches to change individual amino acids on FimH. Thomas and Vogel developed a structural model using steered molecular dynamic simulations describing how mechanical force switches the adhesion strength of FimH from low to high.
"It's quite remarkable, because this force-induced switching is happening at the tip of fimbriae along distance away from the cell membrane," Thomas says. "It makes you wonder how many more proteins exist that are switched mechanically that is a fascinating area for research."
"We need to know how bacterial adhesion is altered by shear. FimH is the second adhesion protein, after fibronectin, for which we have established a structural mechanism for how nature uses mechanical force to regulate protein function. These adhesion proteins thus s
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Contact: Walter Neary
wneary@u.washington.edu
206-685-3841
University of Washington
27-Jun-2002