Bacteria have more to say than previously thought

Bacteria are the oldest living organisms, dating back 4 billion years. So it is only logical that they have evolved ways to communicate.

Yet scientists are just starting to explore the secret languages of these primitive single-cell organisms, whose abundant numbers form most of the Earth’s biomass, and who — depending on species — can both cause and prevent disease in plants, animals, and humans.

One of the pioneer scientific explorers of cell-to-cell bacterial communication is Princeton University microbiologist Bonnie Bassler. The one-time MacArthur Fellow brought an overview of her work to Harvard this week (Feb. 23) in a fast-paced lecture she called “Tiny Conspiracies.”

The title is based on the idea that bacteria talk to one another in order to act in concert — unfolding tiny (cellular) conspiracies that can cause big harm.

A standing-room-only crowd jammed into the Biological Laboratories Lecture Hall for the presentation, part of the Lecture in the Sciences Series sponsored by the Radcliffe Institute for Advanced Study.

“I’m in love with bacteria,” said Bassler toward the end of her fact-packed lecture and slide show, intended for a lay audience.

Part of that attraction has to do with sheer numbers. There are 1 trillion cells in the human body, living alongside 10 trillion bacteria. These teeming masses of unicellular workers make vitamins, power the digestive tract, and bolster the immune system.

Most do “good things for you,” and a few “do bad things to you,” said Bassler. “These are not passive riders.”

For years, bacteria were regarded as unsophisticated, asocial organisms that acted without knowledge of each other. But now we know “bacteria talk to each other,’ she said, “and their language is chemical.”

Bassler illustrated bacterial communication starting with Vibrio fischeri, marine bacteria whose communications are manifest as a bright blue luminescence.

They live symbiotically with bobtail squid in shallow waters off the coast of Hawaii, where moonlight awakens bacterial action in time for the nocturnal squid to go hunting. Lighting the squid’s way are two lobes that fill at the right moment with bioluminescent bacteria.

Alone, the sea-scattered bacteria can’t make much light. But they swarm by the trillions at just the right time to light up the squid, proving a clue to bacterial communication.

In effect, the bacteria are counting each other, said Bessler. They’re waiting for their massed numbers to get high enough to trigger bioluminescence. (She credited J. Woodland “Woody” Hastings for his early work on V. fischeri. He is Harvard’s Paul C. Mangelsdorf Professor of Natural Sciences.)

This chemical counting process is called “quorum sensing” and allows bacteria to synchronize their behavior. The bacteria make a hormonelike molecule, which in high concentrations triggers concerted action.

There are now hundreds of examples of these chemical circuits, which allow bacteria to talk to members of the same species with “exquisite specificity,” said Bassler. They first ask, “How many of me [are] in the environment?”

Understanding the “private language” of a bacterial species is important, she said, since quorum sensing controls pathogenesis. Bacteria need siblings in order to act in concert, mustering enough power to cause harm.

A bacteria’s private language depends on a lock-and-key system in which a hormonelike molecule fits into a receptor in the bacterial cell.

But bacteria can also talk to other species — are “multilingual,” said Bassler. To explore this parallel communication skill, her research team used V. harveyi, a biolumniscent marine bacteria. Unlike V. fischeri, it is forced to live at large in the sea, where understanding the language of other bacteria species is important.

Bassler uncovered a second, parallel, quorum-sensing system — a shared language that she called “the trade language of bacteria, the bacterial Esperanto.” It allows bacteria to poll its alien neighbors who don’t fit the spheres, rods, or spirals of its native species. Bacteria get to ask a second question: “How many of me, how many of them?”

Scientists now think a lot of bacteria have this double-language facility. One lets them count siblings; the other lets them count other species.

Breaking the code of bacterial languages may one day yield an alternative to traditional antibiotics, said Bassler. If a successful infection requires masses of bacteria acting in concert, finding a novel way to impede this “quorum sensing” can interrupt infections before they get dangerous.

She found that a wide range of “clinically relevant pathogens,” including anthrax and staphyloccus, share what she calls the LuxS gene necessary for virulence.

The decreasing effectiveness of traditional antibiotics is “a globally important problem,” said Bassler. An alternative, based on bacterial behavior modification, would be welcome.

She’s looking for molecules that would disable a bacteria’s ability to see or hear, in effect. Her lab has isolated two candidate molecules that seem to have a therapeutic effect, blocking pathogenesis in worms and mice. Human applications are not yet on the horizon.

Beyond applications for infection, Bassler said learning bacterial languages can also lead to treatments for contact lenses, water tanks, meat packaging, and other places bacterial might gather and do harm.

Knowing more about bacterial communication could also lead to ways to strengthen protective bacteria.

“We have all these commensal bacteria that are keeping us healthy,” said Bassler. “Can we make [their conversations] better?”