We've all heard of Pavlov's dogs, the famous canines trained by Russian physiologist Ivan Pavlov to associate food with the sound of a bell. Now, scientists have found that bacteria may be capable of similar behavior--an ability never seen in such simple organisms.

Researchers already know that microbes can mount simple responses to changes in their environment, such as acidity fluctuations, by altering their internal workings. If the changes are regular enough, bacteria can respond ahead of time. But systems biologist Saeed Tavazoie of Princeton University wondered if microbes were capable of more sophisticated reasoning. Could they, for example, learn to match a signal that didn't occur regularly to a probable future event? If so, the bacterium could improve its chances of survival by turning on a preemptive response to that event.

Tavazoie and colleagues first ran a computer simulation to determine if a simple system could evolve such behavior. They created an environment inhabited by evolving virtual bugs. The organisms garnered more energy if they could "learn" that certain signals preceded the arrival of food and launch a preemptive metabolic response. Even when the signal combinations grew more complex, the population was able to evolve the correct responses, the team reports online this week in Science.

The researchers then looked for evidence of this ability in the bacterium Escherichia coli. Because E. coli gets warmer when it enters a human mouth--ferried in on some old meatloaf, perhaps--and then must soon contend with low oxygen levels as it passes into the large intestine, the team reasoned that the bacterium might use temperature as a cue to prepare for the upcoming lack of oxygen. Indeed, when the researchers turned up the heat in a dish of E. coli, the bugs dialed down activity in genes that normally operate in high-oxygen conditions. But the true test came when the team flipped the normal association, growing the bacteria in conditions in which high oxygen levels followed temperature increases. Less than 100 generations later, the bacteria stopped turning on their low-oxygen response after exposure to high temperatures, suggesting that they had evolved to break the association.

The study is the "first convincing demonstration" that bacteria can use environmental cues to anticipate events, says Michael Travisano, an evolutionary biologist at the University of Minnesota, Twin Cities. The work could open up new ways to explain puzzling behavior of microbial pathogens, which might use predictive signals to change their cell surfaces and avoid a host's impending immune attack. "If it does something you don't understand, maybe it's anticipating an environmental shift," he says.