Cracking the code of bacterial communications

Michael R. Silverman, PhD, Emeritus Investigator, The Agouron Institute; Emeritus Adjunct Professor, Scripps Institution of Oceanography

Bonnie L. Bassler, PhD, Squibb Professor and Chair, Department of Molecular Biology, Princeton University; Howard Hughes Medical Institute Investigator

E Peter Greenberg, PhD, Eugene and Martha Nester Endowed Professor of Microbiology, Department of Microbiology and Molecular & Cellular Biology Program, University of Washington School of Medicine

For their combined body of work, Bonnie L. Bassler, Everett Peter Greenberg, and Michael R. Silverman have each been awarded a 2023 Canada Gairdner International Award, which honors outstanding biomedical scientists who have made original contributions to medicine resulting in an increased understanding of human biology and disease.

Bassler, Greenberg, and Silverman were each instrumental in the genesis of an unexpected new field of microbiology: the study of “quorum sensing,” or the means by which bacteria communicate with one another. These researchers have both independently and collaboratively worked to revolutionize the way we think about bacteria, showing that microbes can coordinate with one another to accomplish more than any one bacterium could alone. By overturning the paradigm that microbes only act independently of each other, quorum sensing has allowed new insights into bacterial diseases and the microbiome and its influence on human health.

The first hints of bacterial coordination came out of marine biology research in the 1970s when J. Woodland Hastings and his student Ken Nealson discovered that the marine bacterium Vibrio fischeri produced bioluminescence only when the cells reached a particular population density. That evidence of chemical signaling between bacterial cells went virtually unnoticed until the ‘80s when Silverman and his graduate student JoAnne Engebrecht harnessed the new recombinant DNA technologies to clone and express the genes and proteins involved in the sensory control of bioluminescence. Silverman’s studies revealed the basic regulatory mechanisms controlling collective luminescence and, more broadly, provided the impetus for the discovery of thousands of related systems that underlie group behaviors in diverse bacteria.

Greenberg, who had studied under Hastings and, in 1978, founded his own lab to explore cell communication, says Silverman’s findings provided just what his team had been looking for. “We were off to the races,” he says. He worked to further characterize the genes involved and served as senior author on a 1994 paper that coined the term quorum sensing. He not only showed that this communication existed in other types of bacteria, but he also discovered nearly all major steps in its mechanism.

Bassler—first as a postdoc in Silverman’s lab, and then as the head of her own research group—demonstrated that chemical communication is universal among bacteria, that many different communication molecules are involved, which enable bacteria to distinguish self from others and friend from foe, and in fact, chemical communication transcends the bacterial kingdom boundary. She showed that viruses and higher organisms, including human hosts, participate in these chemical conversations as well. Human gut cells, for example, use quorum sensing to communicate with the bacteria that make up the gut microbiome. Communication enables the microbiome to defend the body against invading pathogens, thereby reducing the severity of bacterial diseases. Bassler also discovered that viruses that infect bacteria can eavesdrop on quorum-sensing signals, which allows them to kill their bacterial hosts when cell density is high—a strategy that maximizes viral transmission to other cells.

“We believe that continuing to study bacterial quorum sensing will lead to wholly new ways to combat infectious diseases,” Bassler says. “We especially want to thwart antibiotic-resistant infections. Because the anti-quorum-sensing compounds my team has invented target behavior, not growth, our hope is that our therapies will be much less vulnerable to the development of resistance compared to traditional antibiotics.”

Silverman, Bassler, and Greenberg all express surprise and delight at the news of their recognition by Gairdner.

“I am almost 80 years old, and I have been retired from lab work for many years, so it is quite jarring to get such unexpected praise,” Silverman says.

Greenberg adds that, while he doesn’t tend to pay much attention to prizes, he knows the prestigious Gairdner banner represents the validation of the burgeoning field of quorum sensing—and will hopefully remind up-and-coming scholars that taking risks can pay off.

“This could have turned out to be a whole lot of nothing,” he says of the early work on bacterial communication. “It speaks to the importance of having an open mind and setting to work on something that just seems really interesting. The Gairdner will bring more attention to the field in general, which will recruit more bright young minds to the issues at hand.”

That inspiration could be the key to unlocking insights we haven’t even imagined yet.

“We have created a new field of research, with hundreds of researchers worldwide now working on quorum sensing,” he says. “And all this since the mid-80s, when there were just two labs working on this. I am amazed at how the field has grown. In all honesty, what excites me about the next decade, after which I will be 84, is to see what all the bright young scientists working in the field discover. You might say that the field now has achieved a quorum, and discoveries will come in left and right.”