Quorum Sensing and Virulence
Following on the heels of my recent post on Bacterial Biofilms, I wanted to write about quorum sensing next. This is a fascinating topic, and understanding how it works helps explain how a bacterium can go from being harmless to pathogenic. To that effect, here is an Open Access review paper on the topic, published in the journal Microbiology.
• Quorum sensing is a mechanism through which bacteria can communicate with one another, by producing and responding to small diffusible signaling molecules. Quorum sensing is used to coordinate gene expression in a bacterial colony, or a biofilm, according to the population density; quorum sensing does not occur if the population of bacteria is too sparse.
• The signaling molecules secreted by the bacteria are known as autoinducers, and they are produced at a basal level; as the bacterial population increases, so does the concentration of the autoinducers. Once the concentration of the autoinducers in the environment reaches a critical concentration, they can bind to and activate receptors inside the cell. Activated receptors can then change gene expression to activate behaviors that are beneficial to the bacterial cell population.
• Quorum sensing was first identified in the marine bioluminescent bacteria Vibrio fischeri where it controls light production. Recently it was discovered that quorum sensing is also involved in controlling bacterial virulence. Given how many human diseases are linked to bacterial pathogens, it is particularly important to gain a deeper understanding of how quorum sensing works.
• It sounds simple but it can be incredibly complex. For example, in Staphylococcus aureus, the autoinducer is a molecule known as AIP which is secreted by the membrane protein AgrB. Once levels of AIP in the environment reach critical mass, it binds to and activates the membrane receptor AgrC, which then proceeds to activate many more genes further along, to make even more AIP, toxin molecules, proteases and so on.
• This system regulates over 70 genes, 23 of which are known virulence factors (virulence factors are molecules that are secreted by bacteria that enable their pathogenesis). These virulence factors can be divided into two groups; the first group aids in attachment to host and immune evasion while the second group is associated with invasion and toxin production. Therefore, the activation of this system switches the bacterium from an adhesive colonizing ‘harmless’ bacteria to an invasive and aggressive pathogen.
• As a counter-measure to quorum sensing, many eukaryotic cells have evolved what is known as quorum quenching. As the name implies, it is the process of preventing quorum sensing by disrupting the signaling. This can be done by degrading the signaling autoinducer molecule; indeed quorum quenching is an extremely attractive method for developing anti-microbial therapies. For more information on quorum quenching, see this Open Access paper.
• Quorum sensing can also be found in other social insects, and can be used as a basis for coordinating the behavior of autonomous robot swarms! Essentially, quorum sensing can function as a decision-making process in any decentralized system.
Here is a great summary video explaining how quorum sensing works: