A few decades ago, scientists believed that bacteria were very basic creatures that did not communicate with each other and were only good at multiplying. Recently, we have realized that this is far from the truth! Bacteria communicate with one another using a language called quorum sensing. You can think of bacterial quorum sensing as the first-ever social network! In this article, we will tell you about the discovery of quorum sensing and how it radically changed our understanding of the microbial world. We will also tell you how our new knowledge of quorum sensing might help doctors to treat dangerous bacterial infections in humans. Join us in this journey exploring the fascinating language of bacteria and how it could benefit human health.
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 . 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.
Box 1 - Our main discoveries on bacterial communication.
In the early 1980s, Mike et al. found the genes that were responsible for bioluminescence in Vibrio fischeri (Figure 1A) . They showed that when the genes were inserted into other types of bacteria, those bacteria become bioluminescent as well! Later on, Peter took the genes that Mike et al. found and inserted them into a type of bacteria commonly used in research, called Escherichia coli, to study the process of bacterial communication . He then showed that other types of bacteria communicate the same way. He also showed that bacterial communication is responsible for virulence in a bacterium called Pseudomonas aeruginosa, which causes dangerous lung infections in people with diseases like cystic fibrosis (Figure 1B). In 1994, Peter et al. coined the term quorum sensing to describe bacterial communication via chemical signals, inspired by the legal term quorum, which means the minimal number of people required to attend certain important meetings. Bonnie, who joined Mike’s lab in 1990, studied another bioluminescent bacterium called Vibrio harveyi and found that it used one autoinducer to communicate with other V. harveyi bacteria, and a second autoinducer that turned out to be a “universal” language, shared by many kinds of bacteria [4, 5] (Figure 1C). Bonnie later discovered more types of autoinducers, and that bacteria use these substances to communicate not only with other bacteria but with other organisms, including viruses . She then showed that interfering with quorum sensing could treat certain bacterial infections in animals .
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.
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 . 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.
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.
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.
- How Bacteria “Talk”—Bonnie Bassler (TED)
- Canada Gairdner International Award Laureates: Drs. Bassler, Greenberg and Silverman
 ↑ Nealson, K. H., Platt, T., and Hastings, J. W. 1970. Cellular control of the synthesis and activity of the bacterial luminescent system. J. Bacteriol. 104:313–22. doi: 10.1128/jb.104.1.313-322.1970
 ↑ Engebrecht, J., Nealson, K., and Silverman, M. 1983. Bacterial bioluminescence: isolation and genetic analysis of functions from Vibrio fischeri. Cell. 32:773–81. doi: 10.1016/0092-8674(83)90063-6
 ↑ Fuqua, W. C., Winans, S. C., and Greenberg, E. P. 1994. Quorum sensing in bacteria: the LuxR-LuxI family of cell density-responsive transcriptional regulators. J. Bacteriol. 176:269–75. doi: 10.1128/jb.176.2.269-275.1994
 ↑ Bassler, B. L., Wright, M., Showalter, R. E., and Silverman, M. R. 1993. Intercellular signalling in Vibrio harveyi: sequence and function of genes regulating expression of luminescence. Mol. Microbiol. 9:773–86. doi: 10.1111/j.1365-2958.1993.tb01737.x
 ↑ Chen, X., Schauder, S., Potier, N., Van Dorsselaer, A., Pelczer, I., Bassler, B. L., et al. 2002. Structural identification of a bacterial quorum-sensing signal containing boron. Nature. 415:545–9. doi: 10.1038/415545a
 ↑ Duddy, O. P., and Bassler, B. L. 2021. Quorum sensing across bacterial and viral domains. PLoS Pathog. 17:e1009074. doi: 10.1371/journal.ppat.1009074
 ↑ Papenfort, K., and Bassler, B. L. 2016. Quorum sensing signal–response systems in Gram-negative bacteria. Nat. Rev. Microbiol. 14:576–88. doi: 10.1038/nrmicro.2016.89