December 13, 2011

New Communication Code Discovered In Disease-Causing Bacteria

Single-celled bacteria communicate with each other using coded messages to coordinate attacks on their targets. Until now, the diversity of codes employed by these invading bacteria was thought to be extremely limited. However, a new report published Dec. 12 in PLoS ONE reveals bacterial communication by a novel, previously undescribed signal type — and, as is often the case in evolutionary stories, some plants have evolved a complementary cypher-breaking detection system that intercepts this bacterial code and uses the information to trigger a robust immune response, preventing disease.

Over the last 20 years, researchers have shown that bacteria employ specific signals to communicate. These signaling molecules, called "bacterial Esperanto" by Professor Bonnie Bassler, an early pioneer in studies of bacterial communication, accumulate in the external environment as the cells grow, and when the concentration reaches a certain threshold level, the bacteria mobilize concerted, group actions.

Until now, it was thought that the two major groups of bacteria (Gram-positive and Gram-negative) use distinctly different types of communication codes. However, the newly discovered signal, called Ax21 and found in a rice-infecting bacteria, doesn't fall into either class. While the previously characterized signals in the bacterial coding repertoire were all relatively small molecules, Ax21 is a small protein, which makes it much larger.

Perception of Ax21 by other bacteria triggers a massive change in their genetic program, altering the expression of nearly 500 genes, or approximately 10% of the bacteria's genome. These changes allow the bacteria to assemble into elaborate protective bunkers, called biofilms, which render the bacteria resistant to dessication and antibiotic treatment. Thus, by virtue of communication and communal living, bacteria increase their chances of survival and proliferation. Ax21 perception also regulates the production of a virulent arsenal, including "effectors" that are shot directly into the host to disrupt its defenses and that initiate motility, allowing the bacteria to colonize new sites for infection.

Most rice plants are virtually defenseless against this Ax21-mediated bacterial attack — except for those plants that carry a particular immune receptor, called XA21, which detects Ax21. This early detection gives the plant time to mobilize its defenses and mount an early and potent defense response. The discovery of a signaling protein from a Gram-negative bacterium with a dual role in bacterial communication and in triggering the host innate immune response has not previously been demonstrated.

The XA21 receptor belongs to a large and important class of immune receptors; the discovery of this class in flies and mice earned Professors Bruce Beutler and Jules Hoffman the 2011 Nobel Prize in Physiology and Medicine. Today's report is the first to show that these receptors can recognize bacterial signaling molecules.

The authors, led by Professor Pamela Ronald at University of California, Davis, have also shown that Ax21 is present not only in important plant pathogens, but also in a human pathogen that infects some hospital patients. This conservation in both plant and animal pathogens suggests that Ax21 also serves as a signal in these related microbes. Furthermore, exploration of bacterial genomes predicts the presence of an abundance of small secreted proteins similar to Ax21 in many other bacterial species, suggesting the intriguing possibility that other species of bacteria also use small proteins to communicate and coordinate infection.

Control of Gram-negative bacterial infections in plants and animals remains a major challenge for the medical profession and for farmers, because conventional approaches are often not sufficient to eradicate these infections.

One major reason for persistence seems to be the capability of most bacteria to grow within biofilms that protect them from adverse environmental factors and antibiotics. The knowledge that bacteria use Ax21 to communicate is expected to lead to new methods for controlling bacterial diseases.


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