Author: Ella Chen
Editors: Sophia Chen, Miriam Heikal
Artist: Chiara Chen
Ever wonder how such tiny molecules like bacteria can carry out such large processes? Unbeknownst to many, bacteria in our bodies communicate with each other through their own “language,” known as quorum sensing. Quorum sensing involves various signaling molecules and occurs throughout the entire body. With the help of quorum sensing, bacteria can coordinate and carry out functions involving whole colonies of bacteria.
Quorum sensing involves the production, detection, and response to autoinducers, which are extracellular signaling molecules that help bacteria respond to changes in population density. As the bacteria reproduce, the concentration of autoinducers in the cell also increases. At low cell density (LCD), the concentration of autoinducers is still relatively low, so nothing happens. However, at high cell density (HCD), which is when the concentration of autoinducers reaches a certain threshold, quorum sensing is triggered. Subsequently, a sequence of chemical reactions, known as a cell signaling cascade, is initiated. The critical threshold at which quorum sensing is triggered varies between each species of bacteria, but the general range is between 106 to 107 cells per milliliter of the surrounding environment. When the autoinducers bind to their respective receptors, the cell signaling cascade causes gene expression, the process by which genetic information is used to create proteins, to be altered. The action of multiple autoinducers making changes in genes allows for certain group-level behaviors to be performed. These behaviors include bioluminescence, biofilm formation, antibiotic production, and sporulation. Furthermore, quorum sensing also initiates a negative feedback loop to regulate the production of autoinducers, ensuring that autoinducer production does not spiral out of control.
Two common bacteria involved in quorum sensing are gram-negative bacteria and gram-positive bacteria. Each type has their own bacterial signaling systems. Gram-negative bacteria have a thinner cell wall, so small molecules can passively diffuse out of their cell wall for quorum sensing. A commonly seen autoinducer molecule in gram-negative bacteria is the acyl-homoserine lactone. On the other hand, gram-positive bacteria have thicker cell walls, which make it harder for molecules to diffuse through. Thus, autoinducers such as autoinducing peptides have to be actively transported through the cell wall through the ATP-binding cassette transporter system. Although the method by which gram-negative and gram-positive bacteria secrete their autoinducers is different, the cell signaling process that they trigger ultimately produces similar functions.
As mentioned previously, quorum sensing can lead to various outcomes, one of which is biofilm formation. Biofilms form when microorganisms or bacteria attach to a surface and essentially create a barrier. Biofilms can trigger the onset of infections such as gum disease, which can result from dental plaque, a biofilm formed on teeth. A notable example of biofilms and quorum sensing is the gram-negative bacteria Vibrio cholerae, which contributes to the secretion of cholera toxin, one of the key factors in cholera disease. After V. cholerae enters a person’s small intestine, it begins to reproduce, which also induces the production of autoinducers. When the cell is at low cell density, meaning that it has a relatively low population in relation to the cell’s volume, autoinducer receptors transfer phosphate to LuxO, or LuxO-P. LuxO is a crucial factor in the creation of biofilms; it promotes the expression of proteins associated with building biofilms. Therefore, when autoinducer levels have not reached the threshold, the bacteria builds its biofilm, preventing antibodies and phagocytes from reaching the harmful bacteria to clear the infection. The infection worsens when the concentration of autoinducers reaches the threshold. However, although the production of the biofilm slows down, the system has activated a signaling cascade that results in the production of cholera toxin, leading to dehydration and severe diarrhea, common symptoms of cholera.
Although quorum sensing is not beneficial to the human body in this case, understanding the role of this process in infections has helped researchers study ways to counteract the negative effects of quorum sensing in pathogenic bacteria like V. cholerae. A study demonstrated that overloading V. cholerae with autoinducers can prevent the process of biofilm formation completely, which then delays the initiation of the process that causes the secretion of cholera toxin enough for a person’s immune system to respond to the presence of harmful bacteria in their system. The results of this study demonstrate the potential for other anti-virulence strategies that target the quorum-sensing process in pathogenic bacteria. Another notable example of an anti-virulence strategy is the one that occurs in Pseudomonas aeruginosa. Ps. aeruginosa is a pathogen that is associated with infections that occur due to cystic fibrosis, a genetic disease that affects the cells that produce mucus. Cystic fibrosis patients produce thicker mucus than normal, which affects the functioning of many organisms. The gene expressions associated with cystic fibrosis virulence are activated by acyl-homoserine lactones (AHLs). A study has shown that furanone, a natural organic compound, can prevent AHLs from activating gene expression during quorum sensing by binding to the quorum sensing receptors and inhibiting the expression of genes that produce virulence factors that cause cystic fibrosis.
The discovery of quorum sensing is still relatively recent and there haven’t been as many studies done on it as on other phenomena, but understanding its role in human health and the onset of diseases is crucial to developing innovative treatments that combat bacterial infections. In particular, disrupting quorum sensing in bacteria provides a promising window of opportunity in responding to antibiotic resistance in bacterial species, an issue that continues to arise as the effectiveness of traditional antibiotics lessens.
Citations:
Mb, Miller, and Bassler Bl. “Quorum Sensing in Bacteria.” Annual Review of Microbiology,
Rutherford, S. T., and B. L. Bassler. “Bacterial Quorum Sensing: Its Role in Virulence and
Possibilities for Its Control.” Cold Spring Harbor Perspectives in Medicine, vol. 2, no. 11, 1 Nov. 2012, pp. a012427–a012427, www.ncbi.nlm.nih.gov/pmc/articles/PMC3543102/,
Windsor, Jon. “How Quorum Sensing Works.” American Society for Microbiology, 12 June
Comments