It doesn’t take brains to have some smarts. New research shows that even bacteria can evolve to predict upcoming events based on clues, like a dog salivating at the sound of the dinner bell.

“It’s really the first evidence that single-celled organisms — bacteria — also have this ability for associative learning,” says Saeed Tavazoie, a molecular biologist at Princeton University who led the research on E. coli bacteria.

The discovery reveals a kind of predictive intelligence in how microbes interpret sensory cues from their environments. Understanding how this predictive ability affects bacteria's behavior could help scientists control microbes better, benefitting industry and the treatment of infectious diseases.

When E. coli enters a person’s body, its environment immediately becomes warmer. Later, as the microbe moves into the person’s gut, oxygen becomes scarce. Tavazoie and his colleagues found that warm temperatures alone triggered the microbes to switch to a less efficient, low-oxygen mode. The bacteria anticipated the coming lack of oxygen and were preparing for it, the researchers reported online May 8 in Science.

This proactive behavior challenges the view that microbes can only react after-the-fact to changes that occur in their environments.

“Sometimes people fall into this trap of sort of thinking that neurons are the only game in town for learning adaptive behavior,” comments Dave Ackley, an artificial life researcher at the University of New Mexico in Albuquerque.

Bacteria obviously have no brains or nervous systems. Instead, the microbes learn through evolutionary changes in their complex networks of interacting genes and proteins. Over hundreds of generations, the “intelligence” needed to predict a coming event based on present clues becomes encoded in these networks.

An individual bacterium can’t learn this way; later generations gain this embedded intelligence over evolutionary time. “Of course microbes can’t tell the future, but they can make educated guesses about the future based on how natural selection and past experiences have shaped their gene regulatory networks,” comments Richard Losick, a microbial geneticist at Harvard University.

Tavazoie’s team also showed that, over many generations, the bacteria can “unlearn” the link between rising temperatures and dropping oxygen. When the scientists grew the microbes in controlled conditions that divorced the rise in temperature from a change in oxygen levels, the microbes stopped anticipating lower oxygen levels after a few hundred generations.

“This new way of thinking about bacteria behavior is important not just in the industrial setting where we want them to do things, make things, but also for infectious diseases where we want to control their growth,” Tavazoie says. Outside of a person, many infectious bacteria become semi-dormant, conserving energy because environmental cues indicate that rough times are ahead. Understanding how the microbes’ gene networks process these environmental signals could lead to ways to trick the bacteria into remaining in a slow-growth mode inside of people as well.

“There’s some hope that we could engineer some changes in environment for them, by the way we design our flu vaccines for example, to sort of fake them out,” Ackley says.

Slowing the microbes down instead of killing them with antibiotics could prevent the spread of antibiotic-resistant strains of diseases, Tavazoie says.

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