Short-circuiting microbe chat

For cellphone-toting humans, the ability to communicate depends on a vast array of technology that includes things like amplifiers and repeaters to speed our words through the ether and ensure their intact arrival at a distant location.

Now, scientists have learned that bacteria use an analogous integrated communications system to sense, retrieve and process the chemical signals they depend on to find nutrients or flee from danger.

The new finding, reported today, Jan. 3, in the journal Nature, may help scientists unravel the secrets of how cells communicate with one another, a development that could, among other things, spur new vaccine strategies or the creation of surfaces that naturally repel pathogenic microbes.

Bacteria – and other types of cells – use receptors on their surface to sense their environment and, like a human nose, pick up chemical cues from a distance, says Laura L. Kiessling, a professor of chemistry and biochemistry and senior author of the paper.

“The receptors act like a sensory organ and help the cell integrate and respond to many different signals,” says Kiessling, who conducted the study with UW–Madison graduate student Jason E. Gestwicki.

Scientists have long known that the membrane-spanning receptors on cells are conduits of chemical information. What they did not know, according to Kiessling, is that clusters of receptors on the cell surface act in concert to “amplify and integrate sensory information.”

In their Nature paper, Kiessling and Gestwicki use a new type of signal, a synthetic multivalent attractant that can interact with several chemoreceptors, to control bacterial responses. They found that the four major types of surface chemoreceptors – each responsible for sensing particular compounds – work as a system to sense their environment and let the cell know whether to move toward or away from the source of a chemical signal.

“They have to collaborate,” says Kiessling. “The whole array of receptors acts to sense a compound.”

The bacterium Escherichia coli, the microbe that is the basis of the UW–Madison study, responds differently to different chemical cues. Sensing a nutrient, the bacteria tend to swim toward the source in hopes of a meal; sensing a potentially damaging chemical, they tend to tumble away from the source.

Kiessling notes that cell chemoreceptors are known to be extremely sensitive, able to detect changes in concentration as low as 5 percent.

The discovery of a collaborative mode of information exchange provides critical insight into how cells in general, not just bacterial cells, can be so highly sensitive to their environments, Kiessling says.

While the study was conducted with E. coli bacteria, similar communication models have been proposed, but not demonstrated, for the key cells in the human immune system.

“The immune system has to respond very sensitively to foreign invaders,” she says, “and if similar signal amplification is in play in humans, it will give us a better understanding of how cell receptors work together” to put the human immune system to work to fight off an infection.

Also, Kiessling notes, a new understanding of the cell communication infrastructure, could lead to general strategies to aid the never-ending battle against pathogenic microbes. For example, it might now be possible to interfere with the signaling processes that make bacteria and other microbes pathogenic, virulent and able to make biofilms.

Interfering with biofilm formation could recast the problem of antibiotic resistance because biofilms harbor antibiotic-resistant bacteria. For example, a bacterial film in the lung causes cystic fibrosis. Short-circuiting the bacterium’s tendency to collect in a film — by hindering its ability to communicate — could underpin new strategies for treating what is now an intractable disease.

The discovery that synthetic compounds can alter bacterial communication could also lead to the development of germ-resistant surfaces for homes, schools and hospitals.

The Wisconsin study was supported by a grant from the National Institutes of Health, and patents for the discovery have been applied for through the Wisconsin Alumni Research Foundation.