The Bacteria Whisperer
Bonnie Bassler discovered a secret about microbes that the science world has missed for centuries. The bugs are talking to each other. And plotting against us.
Trim and hyperkinetic at 40, Bonnie Bassler is often mistaken for a graduate student at conferences. Five mornings a week at dawn, she walks a mile to the local YMCA to lead a popular aerobics class. When a representative from the MacArthur Foundation phoned last fall, the caller played coy at first, asking Bassler if she knew anyone who might be worthy of one of the foundation's fellowships, popularly known as genius grants. "I'm sorry," Bassler apologized, "I don't hang out with that caliber of people."
The point of the call, of course, was that Bassler - an associate professor of molecular biology at Princeton - is now officially a genius herself. More than a decade ago, she began studying a phenomenon that even fellow biologists considered to be of questionable significance: bacterial communication. Now she finds herself at the forefront of a major shift in mainstream science.
The notion that microbes have anything to say to each other is surprisingly new. For more than a century, bacterial cells were regarded as single-minded opportunists, little more than efficient machines for self-replication. Flourishing in plant and animal tissue, in volcanic vents and polar ice, thriving on gasoline additives and radiation, they were supremely adaptive, but their lives seemed, well, boring. The "sole ambition" of a bacterium, wrote geneticist Fran�ois Jacob in 1973, is "to produce two bacteria."
New research suggests, however, that microbial life is much richer: highly social, intricately networked, and teeming with interactions. Bassler and other researchers have determined that bacteria communicate using molecules comparable to pheromones. By tapping into this cell-to-cell network, microbes are able to collectively track changes in their environment, conspire with their own species, build mutually beneficial alliances with other types of bacteria, gain advantages over competitors, and communicate with their hosts - the sort of collective strategizing typically ascribed to bees, ants, and people, not to bacteria.
Last year, Bassler and her colleagues unlocked the structure of a molecular language shared by many of nature's most fearsome particles of mass destruction, including those responsible for cholera, tuberculosis, pneumonia, septicemia, ulcers, Lyme disease, stomach cancer, and bubonic plague. Now even Big Pharma, faced with a soaring number of microbes resistant to existing drugs, is taking notice of her work.
What Bassler and other pioneers in her field have given us, however, is more than a set of potential drug targets. Their discoveries suggest that the ability to create intricate social networks for mutual benefit was not one of the crowning flourishes in the invention of life. It was the first.
The bobtail squid lives in the knee-deep coastal shallows in Hawaii, burying itself in the sand during the day and emerging to hunt after dark. On moonlit nights, the squid's shadow on the sand should make it visible to predators, but it possesses a "light organ" that shines with a blue glow, perfectly matching the amount of light shining down through the water.
The secret of the squid's ability to simulate moonlight is a densely packed community of luminescent bacteria called Vibrio fischeri. Minutes after birth, a squid begins circulating seawater through a hollow chamber in its body. The water contains millions of species of microbes, but cilia in the squid's light organ expel all but the V. fischeri cells. Fed with oxygen and amino acids, they multiply and begin to emit light. Sensors on the squid's upper surface detect the amount of illumination in the night sky, and the squid adjusts an irislike opening in its body until its shadow on the sand disappears. Each morning, the squid flushes out most of its cache of glowing vibrios, leaving enough cells to start the cycle anew.
In the early '60s, Woody Hastings, a microbiologist at the University of Illinois, noticed a curious thing about the V. fischeri grown in his lab. The bacterial population would double every 20 minutes, but the amount of the cells' light-producing enzyme, called luciferase, would stay the same for four or five hours, dispersed among more and more cells. Only when the bacterial population had vastly increased would the flask begin to glow brightly.
From the perspective of a single V. fischeri cell, delaying light production makes sense. The emission of photons is metabolically expensive, as biologists say, and the puny glow of a lone organism is apt to be overlooked in the vastness of the ocean. So how do the cells know when they have reached critical mass? One of Hastings' students, Ken Nealson, theorized that they were secreting a chemical that accumulates in their environment until the group reaches some threshold density. He christened this unknown molecule an "autoinducer." Nealson's hunch turned out to be correct, and the chemical process by which V. fischeri keep track of their own numbers - determining, like a group of senators, that enough members are present to take a vote - was eventually dubbed "quorum sensing."
More recently, scientists have begun to understand that the importance of cell-to-cell communication goes far beyond mere head counting. Many things that bacteria do, it turns out, are orchestrated by cascades of molecular signals. One such behavior is the formation of spores that make bacteria more resistant to antibiotics. Another is the unleashing of virulence. For disease-causing pathogens like Staphylococcus aureus, waiting for a quorum to assemble before getting down to business has distinct benefits. A few microbes dribbling out toxins in a 200-pound host will succeed only in calling down the furies of the immune system. En masse, they can do serious damage. The first "sleeper cells" were bacterial cells.
Hastings, who is now at Harvard, admits that he underestimated the significance of what he saw in his lab. He assumed that quorum sensing was limited to the marine microbes he was studying. "I accepted the view that these bacteria were in a very specific situation," he says, with a burr of regret. "It doesn't take much reflection to think this must occur elsewhere."
The conclusion that only highly evolved organisms have the ability to act collectively proved to be a stubborn prejudice, however. On several occasions, Nealson tried to publish a diagram in microbiology journals illustrating cell-to-cell signaling in V. fischeri, but peer reviewers rejected it. Bacteria just don't do this, the critics told him.
Facebook
Twitter