Michael Sheetz

Until recently, researchers had little understanding of how bacteria like E. coli and Neisseria that cause diseases such as diarrhea, meningitis, and gonorrhea are able to move over human mucosal surfaces to cause infection. Now researchers at Columbia and Oregon Health Science universities have demonstrated how these microbes use threadlike protein filaments to maneuver themselves into position. In addition, these threads called pili, signal to human cells in a process that may promote bacterial invasion. These are some of the conclusions of a study conducted at Oregon Health Science University (OHSU) and published in the Sept. 7 edition of the journal Nature.

The research was performed by Alexey Merz, and Magdalene So, in OHSU's School of Medicine, in collaboration with Michael Sheetz, professor in Columbia's Department of Biological Sciences. Professor Sheetz joined the Columbia faculty from Duke University last February.

Researchers say information about this transport mechanism could ultimately be used to design drugs that interrupt bacterial movement. They believe that disabling the pili could halt infection by preventing the organisms from congregating and invading cells.

"Our findings concluded that pili, tiny hair-like appendages that grab and pull, allow bacteria to congregate into microcolonies when preparing to invade a cell. The introduction of bacteria into the cell can then lead to the spread of disease throughout the host organism," said Dr. So, professor and chairwoman of the Department of Molecular Microbiology and Immunology in OHSU's School of Medicine. "Without this ability to mobilize, these forms of bacteria would not pose a major threat to cells."

In the most novel aspect of the study, researchers were able to measure the mechanical force that bacterial cells exert in attaching to host cells. This was done by anchoring bacteria to a tiny latex bead in a fixed position. A second, even smaller bead was then placed in close proximity to the bacteria and held in place by an intense laser beam, a technique called "laser tweezers." When the pilus filament from the bacteria attached to the bead held in the laser beam, the scientists were able to measure the force with which the bead was pulled out of the laser tweezers.

"For about 30 years it's been known that some bacteria could crawl on surfaces, but the mechanism of crawling has been a mystery," said Merz, who participated in this research as part of his graduate training at OHSU. "Our work provides strong data showing that the pili are what allow the bacteria to move. The bacteria exert the force for crawlingby shortening their pili. It's like a grappling hook. The bacterium casts out a pilus filament, it sticks to something, and then the bacterium hauls the pilus back in to pull itself along."