A bout with a virulent strain of the bacterium Escherichia coli is something most people would go to great lengths to avoid. But last year, 60 brave souls at Stanford University lined up to drink a cocktail of the microbes in an experiment to determine what makes some strains of this bug so nasty. Their sacrifice for science has revealed a subtle feature of the mechanism that enteropathogenic E. coli--a common cause of diarrhea in children in developing countries--uses to colonize the gut.
Stanford microbiologist Gary Schoolnik and his colleagues report in today's issue of Science that hairlike appendages on the surface of the bacterium, known as bundle-forming pili, are critical to the virulence of these bacteria. The pili help the bacteria latch onto a target cell, then bundle together into ropelike filaments that bind a mass of bacteria together at the initial site of infection. The tests also suggest that the pili normally disentangle themselves at a critical stage of an infection so the bacteria can go on to infect new intestinal cells.
Researchers had long suspected from test tube experiments that the pili play an important role in E. coli infections, but Schoolnik's tests are the first to confirm the effects in people. Schoolnik's team produced several mutant forms of the bacterium, one of which produced no pili at all and another produced superpili that bound the organisms together even more tightly than those of the normal strain. They fed various doses of these mutant bacteria and normal bacteria to different sets of volunteers, then compared the effects. The bacteria that lacked pili proved relatively benign and--surprisingly--those with superpili also proved significantly less virulent in causing diarrhea than the normal strain.
When they looked at the progress of an infection in the test tube, Schoolnik's team found that bacterium from the superpili strain remain permanently stuck together in a clump, while clumps formed by the normal strain eventually break up. The researchers conclude that the superpili strain is less capable of going on to establish new sites of infection. "It all links in together very nicely and very logically," says Alan Phillips, pediatric gastroenterologist from London's Royal Free Hospital. "If you can't aggregate and disaggregate then you're not going to colonize very effectively."