In this blog post, we’ll explore the principles by which microorganisms recognize their neighbors and initiate collective behavior through quorum sensing, as well as the characteristics and potential applications of the resulting microbial biofilms.
Have you ever noticed that the surface of a bathtub becomes slippery if it isn’t cleaned for a long time? This occurs because microorganisms proliferate on the surface of the bathtub and aggregate to form a biofilm. A microbial film, or biofilm, can be beneficial or harmful depending on the characteristics of the microorganisms that form it. In order to utilize biofilms created by beneficial microorganisms—or to prevent harmful microorganisms from forming biofilms—we need to consider the characteristics of how microorganisms form biofilms. Microorganisms can exhibit different behaviors depending on whether they exist in small numbers (such as one or two) or in densities above a certain threshold; under specific conditions, they collectively form biofilms once a certain cell density is reached. One of the fundamental principles behind this phenomenon—where microorganisms act collectively to form biofilms—is quorum sensing.
The key to quorum sensing is that microorganisms recognize one another and exchange information. They detect the presence of conspecifics in their vicinity and begin to exchange signals. Although they do not use complex languages like animals or plants, microorganisms also communicate with one another using chemical signaling molecules. This method of communication varies depending on the type of microorganism and the signaling system. To explain this, bacteria can be broadly divided into Gram-positive (+) and Gram-negative (-) bacteria based on the results of the Gram stain. Gram-positive bacteria stain deep blue or purple in a Gram stain, while Gram-negative bacteria stain red or pink. This difference stems from variations in the structure of the cell envelope: Gram-positive bacteria have a thick peptidoglycan cell wall, whereas Gram-negative bacteria have a thin layer of peptidoglycan surrounded by an outer membrane. First, let’s consider the communication system of Gram-positive bacteria. Many species of Gram-positive bacteria produce signaling molecules in the form of small peptides. When these signaling molecules are released outside the cell, nearby microorganisms detect them and receive the signal through receptor proteins located on their cell membranes. The signal is then transmitted to the cell’s internal signaling network, where it regulates the expression of specific genes, potentially triggering collective behavior. In this process, the signaling molecule and the receptor protein recognize each other selectively, much like a lock and key. In other words, only microorganisms with a detection system capable of recognizing a specific signaling molecule will respond to that signal. The basic principle is largely the same for Gram-negative bacteria. However, many Gram-negative bacteria use a class of signaling molecules called AHL (acyl-homoserine lactone). There are several types of AHL, and the signaling molecules used, as well as the systems that recognize them, vary depending on the type of microorganism. This enables selective collective behavior among microorganisms of the same species or within a specific population. In other words, they use a signaling system that functions like their own unique code, and microorganisms capable of recognizing that signal respond to it. However, quorum sensing cannot be explained solely by the distinction between Gram-positive and Gram-negative bacteria. There are also signaling systems, such as AI-2, that are utilized by both Gram-positive and Gram-negative bacteria. Regardless of the type of microorganism or signaling system, a common characteristic is that when a signal molecule they can recognize accumulates in their surroundings above a certain threshold, they detect that signal, interpret it as an increase in the density of neighboring microorganisms, and regulate the expression of genes related to collective behavior. The outcomes of collective behavior vary; microorganisms may emit light, form protective biofilms, or release substances that affect their environment. Through collective behavior, they can perform functions more effectively than when acting individually. Therefore, they initiate collective behavior once a certain cell density or concentration of signaling molecules is reached. These thresholds and signaling systems vary among microorganisms. Since microorganisms are extremely diverse and each has different physiological characteristics and environments, it is difficult to set uniform thresholds for the initiation of collective behavior across all microorganisms.
Given the diversity of microorganisms, their effects on humans can be either beneficial or harmful, depending on the species. For example, while some microorganisms in the human gut influence various physiological functions, including digestion, others cause diseases such as enteritis or stomach upset. These diseases can arise when specific pathogenic microorganisms proliferate or interact with the host; in some cases, the expression of pathogenic factors or the formation of biofilms—which are regulated by microbial collective behavior and quorum sensing—can influence the onset and progression of the disease. As such, microbial collective behavior also poses challenges in the application of microorganisms in science and technology. Consider the formation of a microbial biofilm on a water filter designed to purify water. If a biofilm forms on the surface or inside the filter, it can obstruct water flow or degrade the filter’s performance. This microbial biofilm can also form as a result of microorganisms producing and accumulating extracellular macromolecules through collective behavior. Therefore, it is possible to address these issues by applying or disrupting quorum sensing mechanisms. If biofilm formation is regulated by quorum sensing, the signaling system associated with quorum sensing can be disrupted by interfering with the process by which microorganisms detect each other’s presence or by degrading signaling molecules. In fact, this approach is called “quorum quenching,” and research is underway to degrade or modify signaling molecules so that microorganisms cannot normally detect each other’s signals. As suggested in the original text, a method that uses other microorganisms or enzymes to remove the chemicals that microorganisms use to detect each other’s presence can also be considered an example of this approach. Since the substances and signaling systems used vary depending on the type of microorganism, applying this method requires first identifying which signaling molecules are used and how those signals are detected.
In conclusion, quorum sensing plays a role similar to microbial communication. To transcend the limitations of individual behavior and engage in collective action, microorganisms detect the presence and density of their neighbors, exchange signaling molecules, and confirm the status of their group. The results of this collective behavior can be utilized in very important ways in science and technology. However, because there are so many different types of microorganisms, the outcomes of their collective behavior and the signaling molecules that regulate it are also diverse. Consequently, research is currently underway on the various chemical signaling molecules and signaling pathways that microorganisms use in the quorum sensing process. Additionally, research is being conducted on methods to disrupt quorum sensing by degrading microbial signaling molecules or interfering with the signaling process. If we gain a deeper understanding of quorum sensing through these efforts, we will be able to use this knowledge to induce microorganisms to form biofilms or, conversely, prevent them from doing so; we will also be able to regulate their collective behavior, such as inducing or inhibiting the production of specific substances. We look forward to active research in this area deepening our understanding of microbial collective behavior and enabling its beneficial application across various fields of science and technology.
