Drs. Bonnie Bassler, Michael Silverman, and E. Peter Greenberg were awarded the 2023 Canada Gairdner International Award for their discoveries of how bacteria communicate with each other and surrounding non-bacterial cells, providing new insights on how microbes behave and opening up exciting directions for developing new drugs against infectious diseases.

Glowing Bacteria Reveal an Ancient Language

Our story begins with a tiny glowing bacterium. In the 1970s, Ken Nealson and Woody Hastings found that a bioluminescent marine bacterium called Vibrio fischeri made light only when many bacteria of the same species were close together [1]. These scientists also noticed that, when a large enough group of V. fischeri were present, they all started making light at the same time. The scientists hypothesized that the bacteria were producing a chemical called an autoinducer, and when there were enough bacteria close to each other, the concentration of the autoinducer got high enough to switch the light on. This was a radical new idea because it meant that bacteria were communicating with each other—these organisms were previously thought to be simplistic “loners” that had no way of communicating.

Then, the three of us (Peter, Mike, and Bonnie) worked for a few decades to uncover the secrets behind this bacterial communication and proved that Ken Nealson and Woody Hastings were right (Box 1). Bacteria constantly communicate and share surprisingly complex information about themselves and their environments—not only with one another, but also with other cells and organisms.

Quorum Sensing—The World’s Earliest Communication

Bacteria are the oldest organisms living on Earth. They have about 5,000 genes, and up to 600 of those genes are controlled by quorum sensing. This means that up to one fourth of the bacterial genome is like an orchestra that is conducted by quorum sensing. In an orchestra, the conductor does not want all the instruments to play at once—at a certain moment, she might want the violins to start playing, and at another moment she might want to add the brass instruments. In the bacterial orchestra, the same thing applies: certain gene “instruments” are activated at different autoinducer concentrations. At other times, when autoinducer concentrations are different, some genes might “stop playing” and be switched off.

Quorum sensing was the first communication method to develop on Earth. It is also the earliest social behavior seen on Earth. Bacteria are so tiny that they cannot do much by themselves. But when they use quorum sensing to send and receive information about how many bacteria are around them and about how related they are to each other, they are acting more like a multicellular organism.

We now know that there are at least four types of autoinducers, or “chemical words,” in the quorum sensing language (Figure 2). One type is unique in every species of bacteria, and it allows bacteria to communicate with members of their own species. Using this autoinducer, one bacterium can tell another, “you are my twin.” Another type of autoinducer is made only by genetically close (but not identical) bacteria, and it says, “you are my relative.” A third type is made by many types of bacteria, and basically says, “I am a bacterium.” This autoinducer is used to communicate with other species of bacteria. We think that bacteria count the total number of bacteria that are present in their environment. They can even use this third type of autoinducer along with the first type to compute whether their species is the majority or minority in the environment, by dividing the number of “twin” autoinducer molecules by the number of “bacteria” autoinducer molecules. The most recent type of autoinducer discovered is made of two molecules that say, “you are a eukaryote” and “you are a virus.” Using these four different “words,” bacteria can recognize others of their own species, know when there are other species of bacteria around, and identify other types of organisms.

New Antibiotics?

Quorum sensing can play an important role in human health, as it is used by harmful, disease-causing bacteria. Disease-causing bacteria have specific genes that make them virulent, and these genes are controlled by quorum sensing. For example, some bacterial genes help bacteria create hard-to-kill communities called biofilms, and others help them release their toxins at the right time, to most effectively attack their host. Normally, bacterial infections are treated with antibiotics designed to kill the bacteria or stop them from multiplying. But there are always a few bacteria that are not affected by the antibiotic, and these antibiotic resistance bacteria remain alive and keep multiplying within the body (to read more about antibiotic resistance, see this Frontiers for Young Minds article). Might there be another way to neutralize harmful bacteria? Maybe there is a way to disrupt their communication so that they become less harmful?

Scientists are currently working on new antibiotics that prevent bacteria from detecting or producing autoinducers, thereby blocking their communication (Figure 3). When quorum sensing is blocked, bacteria are much less harmful because they can no longer coordinate their harming activities. Unlike “regular” antibiotics, drugs that disrupt quorum sensing do not interfere with bacterial growth and do not kill bacteria, so scientists hope that it will take bacteria much longer to become resistant to antibiotics that target quorum sensing.

What Else Can We Do With Quorum Sensing?

Quorum sensing research is developing rapidly, and we keep finding new quorum sensing molecules with very different properties. These molecules may contain more complex information than we initially thought! One fascinating area to study is the communication between bacteria within the human microbiome, which is the entire collection of bacteria and other microorganisms in the human body [6]. The human microbiome can communicate with the body, and it is so crucial to the body’s healthy functioning that it is now thought of as another organ—even though it is made of non-human cells. For example, the gut microbiome interacts with the immune system and other bodily systems and may even influence mental health. We would like to be able to “eavesdrop” on the interactions between bacteria, and between bacteria and other microbes in the gut microbiome—like investigators listening in on suspects’ phone calls. Mapping the communications between organisms in the microbiome might lead to important insights about human health.

We also want to use quorum sensing to study how communities of bacteria cooperate with each other and how they deal with “cheaters” that do not play by the “rules.” These cheaters do not help produce necessary substances which the whole community uses, but they still consume them. This makes cheaters more fit than cooperators, because they enjoy these necessary substances without having to invest energy into their production. If being a cheater is so profitable, why do the cheaters not take over the population? It turns out that cheaters do not activate the genes controlled by quorum sensing—which makes them not produce necessary substances, but also makes them vulnerable to a toxin that is released in the population. Cooperators that do activate quorum sensing genes activate a gene that makes them more resistant to this toxin, so they are significantly less affected by it. This is how populations of bacteria maintain cooperation, and we think we can use this molecular-level knowledge to understand other types of cooperation seen in nature.

Loving Nature

The three of us share a great love for nature, and we chose to express this love through science—but there are many other ways to study or work with nature that are also very fulfilling and gratifying. Some of you might want to be doctors; others might enjoy traveling into the jungle and watching exotic animals. Whichever choice connects you with the beauty and wonder of nature is a great path to follow.

If you choose the scientific path, you can view it like a treasure hunt. The “treasures,” or big eureka moments that we experience and scientific discoveries that we make, are extremely important and exciting, but they may not happen very often. To find them, we usually work for long periods of time with no positive results. During these times, we must find ways to stay curious and enthusiastic as we “hunt” for the next treasure. Even after we find a treasure, it often takes time for other scientists—or even the scientists who made the discovery—to appreciate what was found. This certainly happened with quorum sensing, and it is frequently the case with any brand new science—it takes time for enough data to accumulate to make an impact. Luckily, we had great colleagues and students that love nature as much as we do, and this made our entire journey fun.

Young people often think that they can never be as successful as we are. The truth is that we were just like you when we were students a few decades ago! It takes time to become a good scientist. We think that any student can become like us, if they stay dedicated to their work for as long as we have been. While it can be useful to have scientific idols that you want to become like 1 day, we also think that, at each stage in your career, you should also choose role models who are closer to where you currently are—these people could serve as steppingstones toward your end goal.

Glossary

Bioluminescent: ↑ A word that describes a living organism that produces and emits light.

Autoinducer: ↑ A chemical that is used in bacterial communication that helps bacteria count other bacteria and other organisms in the environment.

Virulence: ↑ The ability of bacteria (and other microorganisms) to damage the organisms they infect.

Quorum Sensing: ↑ A type of bacterial communication using chemicals called autoinducers. Quorum sensing is responsible for group behaviors of bacteria, such as bioluminescence and virulence.

Biofilms: ↑ Groups of bacteria that stick to each other and to various surfaces, such as the insides of the intestines.

Antibiotic Resistance: ↑ The trait of bacteria that are insensitive to certain antibiotics and can still multiply in the presence of those drugs.

Microbiome: ↑ All the microorganisms that are living in a particular environment, such as the human gut.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Additional Materials

1. How Bacteria “Talk”—Bonnie Bassler (TED)
2. Canada Gairdner International Award Laureates: Drs. Bassler, Greenberg and Silverman

Acknowledgments

We wish to thank Noa Segev for conducting the interviews which served as the basis for this paper and for co-authoring the paper, and Iris Gat for providing the figures.