Learning the language of bacteria

Bacteria are among the simplest organisms in nature, but many of them can still talk to each other, using a chemical "language" that is critical to the process of infection. Sending and receiving chemical signals allows bacteria to mind their own business when they are scarce and vulnerable, and then mount an attack after they become numerous enough to overwhelm the host's immune system.

This system, called "quorum sensing," is an interesting example of sophistication among microbes, says Helen Blackwell, an associate professor of chemistry at the University of Wisconsin-Madison. In practical terms, she adds, quorum sensing may provide an alternative therapeutic target as bacteria continue to evolve resistance to antibiotics.

Theoretically, blocking quorum sensing would prevent the bacteria from turning pathogenic and producing the toxins that are an immediate cause of disease in bacterial infections.

Bacteria use simple chemical signals to control quorum sensing, and Blackwell is interested in how these compounds work and in developing new ways to intercept them. In a study just published online in the journal ChemBioChem, Blackwell and colleagues Andrew Palmer, Evan Streng and Kelsea Jewell showed that several species of bacteria can respond to identical signals, suggesting that one drug could battle quorum sensing in several types of bacteria. Many bacteria use a class of molecules called lactones for quorum sensing, and Blackwell's lab has synthesized many non-native lactones, and then tested them in two species of bacteria that use identical native lactone signals. Overall, the organisms responded similarly to the same synthetic molecules, despite the dramatic differences between the species. These results suggest that the same basic chemical sensing mechanism could be common among microbes, Blackwell says. "That tells us that we can use these classes of chemicals to study — and perhaps eventually fight — a much broader range of bacteria."

Finding a broad-spectrum activity for the synthetic lactones is good news, Blackwell adds. "Bacteria come in countless varieties, and the ability to target multiple organisms with one compound could streamline the search for drugs. At the same time, we also have found differences in signal selectivity that may allow us to target some bacteria while ignoring others." That could provide the best of both worlds, Blackwell says. One drug might halt multiple infections, but related drugs might affect only one microbe in a mixture. "The data indicate that it should be possible to design and use compounds that are either selective or broad-spectrum."

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