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.
By Steve Silberman
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 François 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.
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