MSU Scientists Eavesdrop On Bacterial

BOZEMAN, MT--If bacteria could talk, their conversations might go something like this:

"Stay with us , in this nice place, and make slime or we'll all float off and starve to death." Or, "It's too crowded here. Let's colonize somewhere else."

Bacteria, in fact, do speak a chemical language, and scientists at Montana State University and elsewhere have reported discovering the first few words that govern the growth of bacteria in sticky clusters called biofilms.

The group has published its findings in the April 10 issue of the journal Science . The scientists are David Davies and William Costerton at MSU; Matthew Parsek and Pete Greenberg at the University of Iowa; and James Pearson and Barbara Iglewski at the University of Rochester, New York.

Although not a household word, biofilms are an everyday occurrence, especially in industrial and some medical settings. They clog pipes and foul the hulls of ships. They can create chronic infections in catheters and artificial valves and joints. They may be responsible for ear infections in youngsters. And it's been known for a long time that they rot your teeth.

With today's report, scientists have begun talking cautiously about controlling biofilms not with toxic biocides and antibiotics but by disrupting their own natural messaging system.

"In general, the idea is that we have discovered that bacterial behavior can be modified chemically," said David Davies, the paper's lead author. "These chemicals come from the bacteria themselves."

But first, a bit about bacterial habits. Almost since the time of Louis Pasteur, scientists have thought about and studied bacteria as individual cells floating freely through the bloodstream or in saliva or in a creek.

But most bacteria don't live this planktonic lifestyle. Most live stuck on surfaces in clusters held together by a sticky, gelatinous matrix. These communities are called biofilms. If you've ever slipped on a rock in a stream, you've met a biofilm. When looking through a microscope, scientists have described biofilm communities as elegant arrays of channels and spires.

Several years ago, Davies and MSU microbiologist Gill Geesey learned that the planktonic bacteria throw some kind of genetic switch when they hit a surface, which is their cue to form a biofilm. When they break away from the colony they undergo another biochemical change and revert back to the planktonic, free floating type.

"But there still was one unanswerable question: How could they have such a complex [biofilm] structure without cell-cell signaling," said Bill Costerton, who heads the MSU Center for Biofilm Engineering.

Today's report of cell-cell signaling represents the first words in what may be a large chemical vocabulary dictating how bacteria do what they do in biofilms and why. The paper is the first to report on bacterial communication in biofilms, said Davies, although bacterial communication in other settings, like the kind that produces light in a flashlight fish, was uncovered in the 1970s.

"We now know the words for biofilm formation and for the destruction of biofilms," Davies said. He suspects there also are words to turn on or off specific feeding mechanisms, to accelerate or slow down growth or to make specific enzymes that degrade toxic chemicals.

Davies zeroed in on two chemicals, called homoserine lactones, in a common biofilm maker called P. aeruginosa. P. aeruginosa is the No. 1 cause of hospital acquired infections, the chief organism in burn and open-wound infections and a key player in infections in cystic fibrosis patients, according to Davies.

The bacteria are excreting homoserine lactones all the time, but when enough bacteria gather, something called quorum sensing occurs. The homoserine lactones start to diffuse back into the cells and trigger genetic changes within the bacterium. The bacterium starts making slime and a biofilm results. The signalling process takes about 15 minutes, said Davies.

When working with P. aeruginosa that couldn't make this quorum-sensing chemical, Davies could grow only wimpy biofilms. They lacked the complex and resilient slime structure that characterizes a healthy bacterial community.

"This shows that the biofilms we all know and love are determined by the presence of these molecules," Davies said. "If we can knock out the ability to communicate we can disperse the biofilm."

Costerton said the discovery of communication molecules in biofilms extends into the bacterial world what's already known about the role of signaling molecules such as pheromones and hormones in the animal world.

"We could get quite subtle in our approach to bacteria," he said. "We're used to killing them. Now perhaps we could just disrupt or manipulate them."

An official from the National Science Foundation (NSF), which funds the MSU biofilm center, called the discovery "an exciting event."

"We're on the brink of a brand new technology," Fred Betz, an NSF program officer, said recently after hearing Costerton and Davies talk about their work. "It may be simple. It may be complex. But that's the next step."

The agency has begun funding the next step--the development of chemical messages that would confuse the bacteria and usher in a new way of treating bacterial infections, for example. The MSU biofilm center and the Center for Marine Biofouling and Bioinnovation at the University of New South Wales, Australia, are collaborating on the project.

"It's all still theoretical," cautions Davies. "But this is the area we are inexorably marching toward with this kind of research."