Proteins do all the business of cells, including energy transfer, which a couple of different systems handle, according to Larsen. The TonB system, which controls certain "gates" in the outer membrane, is a good model for resolving questions of how a protein recognizes and communicates with others with whom it's exchanging energy, he says. A similar system, called the Tol system, is important in maintaining the defensive barrier, although which proteins it delivers energy to as part of that process isn't known.
Finding that answer is a long-term objective, he adds, saying it could help lead to the development of a drug that could break the barrier.
Some drugs already target the outer defenses of bacteria. Perhaps best known is penicillin, one of several existing antibiotics that successfully target specific structures required for the barrier function to work, Larsen notes. The outer membrane is stabilized by a grid of sugar polymers, and penicillin wrecks the grid, making the cells susceptible to a body's natural defenses.
Disrupting energy flow--knocking out the TonB and Tol systems--would provide another powerful weapon against disease-causing bacteria, he says, but researchers must first understand how the two systems work. They are similar enough that they have some relatively interchangeable parts, but they don't swap perfectly. He compares the situation to two people speaking different dialects of the same language--"not everything makes total sense." But the TonB-Tol "cross talk" does provide a tool for mixing and matching parts of the systems and asking what's important and what isn't.
"To begin understanding how proteins talk, we first made random mutations--we broke things and then asked what happened," Larsen says. "That strategy worked well and allowed us to identify the key 'words.' Now we want to know what the 'words' mean, and w
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Contact: Scott Borgelt
sborgel@bgsu.edu
419-372-8582
Bowling Green State University
21-Aug-2006