by Molly Sargen
figures by Molly Sargen and Aparna Nathan

Despite the apprehension one may feel about working in groups, it’s hard to deny that groups are able to do some things individuals cannot. Hundreds of studies have found that working in groups has many benefits, including increased creativity and productivity. Many other studies have aimed to determine optimal conditions for group work. Importantly, most agree that good communication is key to successfully working in a group. 

It appears microbes discovered the benefits and utilized effective strategies of working together long before humans realized the merits of teamwork. Many microorganisms use a form of molecular communication called quorum sensing to coordinate group behavior to achieve tasks that would be impossible for a single organism. 

Discovery of quorum sensing

Quorum sensing was first observed in bioluminescent bacteria. Scientists working with Aliivibrio fischeri (also known as as Vibrio fischeri) realized the bacteria emitted light only during distinct phases of growth. In a freshly inoculated culture, when there were few bacteria, the bacteria did not emit light. As the bacteria multiplied, the density of the culture increased and the bacteria began to emit light.  Researchers determined that the bacteria produced the enzyme responsible for bioluminescence, luciferase, only when the number of A. fischeri in the culture reached a threshold density. They called this density-dependent behavior autoinduction (“self”-induction) because the bacteria stimulated peers of the same species to produce luciferase. 

Figure 1: Bacteria produce bioluminescence only when the density of bacteria in the culture reaches a certain level. A) At inoculation there are few cells in the culture. B) As cells divide, the density of cells increases. C) At high density, the bacteria produce an enzyme responsible for bioluminescence.

Later, other scientists discovered the genes and signaling molecules responsible for autoinduction. The signaling molecules became known as autoinducers because the bacteria respond to the same molecules they release. Each bacterium releases signaling molecules to say, “Hey, I’m here!” to other members of their species. Nearby, kin bacteria receive the signal and also send out their own copies of the same molecule. When more bacteria are present, there are more autoinducers in the environment and each bacterium receives more copies of the signal.  When the bacteria have received enough signals, they know when enough of their peers are nearby and they can start working together. At this time, each bacterium changes its gene expression to contribute to the group effort. As a result, the population is able to perform tasks that are impossible for single cells. For A. fischeri, this means producing luciferase to provide light in its natural environment. 

This process was likened to a committee needing a quorum, or a certain number of members present, to make a decision. Autoinduction therefore became popularly known as quorum sensing. 

Figure 2: Bacteria send and receive signals to communicate cell density. A) A bacterium sends a signal to say, “Hey, I’m here.” When cell density is low, neighboring cells receive only a few signals and recognize that there aren’t enough bacteria to complete a group function. B) When the cell density is high, each cell receives many signals and knows the population is large enough to perform group functions.

Quorum sensing in nature

Subsequent work has discovered dozens of quorum sensing molecules and their unique receptors, revealing the multitude of bacteria that use quorum sensing for diverse purposes. In nature, A. fischeri, the bacterium mentioned above, lives mutualistically in the light organ of the Hawaiian bobtail squid and other light-dependent marine animals. The squid uses the bioluminescence from the bacteria as a light source in dark marine environments. In turn, the bacteria receive nutrients from the squid. 

Other bacteria use quorum sensing during infections. Vibrio cholerae, the bacterium responsible for cholera, uses quorum sensing to control a cycle of infection. Depending on the number of bacteria present, V. cholerae produces toxins to combat attacks from immune cells or cause the diarrhea associated with cholera. In this way, V. cholerae can establish an infection in one host and escape the infected individual to infect new hosts.

In a different strategy, the opportunistic pathogen Pseudomonas aeruginosa uses quorum sensing to form biofilms. Biofilms are resilient structures composed of bacterial cells and a strong matrix. For example, dental plaque includes biofilms made by oral bacteria. Pseudomonas infections are often deadly for patients with cystic fibrosis or burn wounds because the matrix of the biofilm protects the bacteria from immune cells and antibiotics. 

Figure 3: A) Bioluminescent bacteria growing on a petri dish. B) A microscopic view of a biofilm shows bacteria surrounded by a protective matrix.

Although group behaviors are ultimately beneficial for the population, they require an immense amount of energy input from each individual. Consequently, it is important for bacteria to attempt these feats only when enough bacteria are present to accomplish the task. Consider that if a single bacterium hypothetically emitted light, you would not notice. However, when a whole culture of bacteria produces bioluminescence, it’s striking. 

The molecules of quorum sensing

The specificity of quorum sensing molecules and receptors is important for carefully controlling the group behaviors mentioned above. Most environments are complex communities that contain many species of microbes. In these communities, signaling molecules from all the microbial members create a lot of molecular noise–akin to a room full of people speaking different languages. Although many quorum sensing molecules are very similar, each bacterium’s receptors detect only specific molecules. This allows each bacterium to clearly communicate with its peers through the cacophony of surrounding molecular noise.

Figure 4: Many quorum sensing molecules share very similar structures. Small differences (highlighted in red) enable bacteria to distinguish each molecule.

Interestingly, scientists have recently discovered quorum sensing molecules shared between multiple species of bacteria. While the full implications of this shared molecular dialect remain unclear, it has been speculated that this might allow bacteria to understand the composition of other bacteria in their community. This crosstalk might help multiple species work together for tasks such as building a multispecies biofilm. In other words, a common signaling molecule may unify bacteria with the capability to contribute to the same group activity. Thus, rather than identifying only peers of the same species, each bacterium recognizes the presence of any bacteria that might cooperate.

Furthermore, scientists are also learning that other organisms can intercept bacterial quorum sensing signals. For example, viruses that infect bacteria monitor bacterial autoinducers when choosing between actively killing the bacteria or passively hanging out inside the bacteria. Because the virus needs a bacterium to survive, it’s better for the virus to initiate active infection at a higher density of bacteria where new hosts are available. Likewise, plants may produce antibacterial chemicals to protect themselves after detecting certain bacterial quorum sensing molecules.  

Outlook

Quorum sensing remains a fascinating area of research. Bacteria are the most well-characterized example of quorum sensing. However, some higher organisms, such as yeast, also use quorum sensing systems. Controversially, some groups have applied the term quorum sensing to population-dependent responses in multicellular organisms as well.

Some work suggests targeting quorum sensing might be a way to manipulate bacterial systems. For example, if we block the bacteria’s ability to send or receive their quorum sensing signals, they won’t be able to perform group functions. This is called quorum-quenching and could be used to treat or prevent infections. A promising application of quorum-quenching is the use of synthetic molecules such as 5-fluorouracil (5-FU) to prevent the formation of biofilms on medical devices where they might infect patients. Alternatively, there are times when we might want bacteria to work together. For example, quorum sensing in Rhizobacteria could improve soil quality and promote the growth of plants. Whether or not we learn enough to safely manipulate it, communication between single-celled organisms is an outstanding example of the power of teamwork.


Molly Sargen is a first-year student in the Biological and Biomedical Sciences (BBS) Ph.D. Program at Harvard Medical School.

Aparna Nathan is a third-year Ph.D. student in the Bioinformatics and Integrative Genomics Ph.D. program at Harvard University. You can find her on Twitter as @aparnanathan.

Figure Sources: 

Figure 1 and 2: Created with Biorender.com by Molly Sargen

Figure 3A: “IMG_0196” by Cambridge iGEM is licensed under CC BY-NC-SA 2.0

Figure 3B: “Biofilm” by AJC1,  licensed under CC BY-NC-SA 2.0 

Figure 4: Created by Aparna Nathan 

Cover Image:  “Cholera bacteria (Vibrio cholerae)” by Sanofi Pasteur is licensed under CC BY-NC-ND 2.0 

For More Information:

  • I highly recommend Bonnie Bassler’s TED Talk, “How bacteria ‘talk’”  for an entertaining description of quorum sensing. 
  • Watch Woody Hasting’s talk for iBiology to learn about how his lab discovered quorum sensing. 
  • Read about the role of quorum sensing in soil health here
  • Read about how scientists are trying to manipulate quorum sensing in animals’ microbiome here
  • Read about how viruses intercept quorum sensing signals here
  • For more detailed information about the molecular aspect of quorum sensing see the associated page from Biology LibreTexts. 

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