Feb. 6, 2002 A discovery by Princeton scientists could lead to new ways to combat biofilms -- tough coatings of bacteria that form on everything from teeth and prosthetic devices to the hulls of ships.
Biologists Karen Otto and Thomas Silhavy found a mechanism bacteria use to sense when they have touched a solid surface, which sets into motion the process for building a film. Their study of E. coli identified a protein on the surface of the bacteria that initiates biofilm formation, plus a two-protein receptor system that receives and transmits the signal within the cell.
"In a sense, you can say that for E. coli this is a touch sensor," said Silhavy, a professor in the Department of Molecular Biology. "If we mutate these genes, the bacteria don't attach as well and, if they do, they attach in a different way."
A paper describing the results is appearing in the Feb. 5 online edition of the Proceedings of the National Academy of Sciences.
The results suggest that disrupting this sensing mechanism may be an effective strategy for developers of drugs or other antibacterial agents aimed specifically at biofilms. When bacteria join together as a biofilm, they become much more resistant to antibiotics than when they were free-floating, said Silhavy.
Many kinds of bacteria commonly found in liquid environments naturally form biofilms when they meet a solid surface. Biofilms often occur on teeth where, if not removed, they become part of plaque and lead to decay. They also can pose a problem on any artificial surface implanted in the body, such as prosthetics and catheters, which can be difficult to treat with antibiotics. Biofilms corrode pipes, infect heating and cooling devices and slow down ships by making the hulls move less smoothly through the water.
Otto, a postdoctoral researcher in Silhavy's lab, used a variety of techniques to pinpoint the touch-sensing mechanism. First, she created a strain of bacteria with an easily detectable marker attached to the genes they wanted to study. Whenever the bacteria used those genes, the marker became visible. Otto exposed a vial of bacteria to tiny glass beads, which triggered the attachment process. In the first hour, the activity of the receptor system went way up, but did not change for bacteria that were free floating.
Otto and Silhavy then genetically engineered bacteria to lack the genes in question. With each gene deletion, the bacteria did not attach as well.
"Without these genes, they can't adapt to life on a surface," said Otto. "It's clear that when cells turn on these genes, they adapt to a different environment."
More than just an accumulation of bacteria, biofilms are complex structures in which the bacteria are likely to use a substantially different set of genes than in their free-floating form, said Silhavy. This community of bacteria, which often includes many different strains, gives protection against antibiotics and other hazards, and at the same time allows the efficient transport of nutrients.
"It's not just a glob," said Silhavy. "They actually build a little structure on the surface, so nutrients can get inside the biofilm."
To analyze the formations their bacteria made, the researchers used a measuring device called a quartz crystal microbalance. The device has a vibrating crystal that is very sensitive to anything that touches it. As bacteria attached to the crystal, the researchers could measure not only how many cells were attached, but also how rigid a structure they formed. This test showed that when the mutated bacteria did attach to surfaces, they did so in a way that did not resemble biofilms.
"In fact, they were a lot like dead cells," said Silhavy.
The next stage in the research, said Silhavy, is to investigate further along the chain of reactions and find out what mechanisms are activated after the initial touch sensor and receptor system that he and Otto identified.
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