Climbing Gear for Bacteria
On the battleground of infectious disease, every bacterium is a little soldier. It must be specially equipped to handle the microterrain and conditions in the host's body if it's to mount a successful invasion. From the bacterium's perspective, some of the most hostile environments are those found in the digestive and urinary tracts, where the shear forces of flowing fluids threaten to sweep an invader into oblivion. Yet certain strains of Escherichia coli routinely achieve victories on these battlefronts—at least as measured by the millions of cases of diarrhea and bladder infections caused by E. coli every year. What's their secret weapon?
It turns out that E. coli has evolved specialized gear that allows it to hunker down when the going gets tough. It's been known for decades that E. coli must stick to the surface of a tissue before it can infect the body. Defensive actions by the host, such as sneezes, urination or mucosal secretions, are generally supposed to help vanquish the microbial invaders before they get too far inside defensive lines. But Wendy Thomas and her colleagues at the University of Washington recently discovered that E. coli actually hold on more tightly when the shear stresses imposed by flowing fluids are high (Cell, June 28).
It seems that the bacteria resist most when body fluids are trying to push them away, but then let go when the force is not threatening, and so can move against the flow toward their target. This defies conventional wisdom, which has always assumed that bacteria would have a more difficult time adhering to a surface in the face of shearing forces.
The trick of holding tight seems to involve a "sticky" molecule, called FimH, which is located at the tips of long, hairlike extensions (fimbriae) on each E. coli cell. Thomas and her colleagues found that the FimH molecule isn't just a passive piece of equipment—like, say, a rock-climber's piton; rather, it changes shape in response to local conditions. Computer simulations of FimH reveal that the molecule stretches in response to increasing shear, and so acts as a force sensor (see model, right). The scientists suggest that stretching might change the shape of the FimH molecule in such a way as to expose a previously hidden binding site or perhaps change the shape of the binding site from low to high affinity. In effect, FimH transduces shear-induced mechanical stress into a chemical change.
This makes FimH especially interesting, because scientists generally think of a protein as either binding or not binding. But FimH is able to do either, and it seems to be a tool perfectly designed for its task. The E. coli bacterium is not only a soldier, it is also a consummate nanotechnologist. No wonder it has proved to be such a formidable adversary.—Michael Szpir
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