CH391L/S13/QuorumSensing: Difference between revisions

Quorum sensing is a system used by bacteria to detect population density and respond.  This communication is carried out by molecular signals produced and released by the bacteria. The signals disperse to nearby individuals and eventually lead to a pathway that causes induction of more signal production in those neighbors, in addition to other desired genes . The more dense the population, the higher concentration the signal is. This circuit creates a positive feedback loop that causes the population to work in sync. In nature, bacteria can use quorum sensing for functions such as bioluminescence , virulence , and biofilm formation . Because quorum sensing is such an important aspect of biofilm formation, it is a valuable topic of research for disease prevention and treatment. In addition, QS has various applications in synthetic biology since QS systems can be engineered to accomplish useful tasks.

''V. fischeri'' is a classic example of gram negative bacterial quorum sensing . The system uses two regulator proteins that have analogies in other QS systems, LuxI and LuxR. LuxI is a protein that synthesizes the signal, N-(3-oxohexanoyl)-homoserinelactone (HSL), called the autoinducer. The autoinducer then diffuses out of the original sender and into neighboring cells. If ''V. fischeri'' density is low, there is a low HSL concentration. Similarly, at high densities, there is high HSL concentration. At a particular threshold concentration, HSL will bind to and activate LuxR, a protein which activates transcription of a set of genes that include bioluminescence and ''luxI''. ''luxI'' transcription leads to further production of LuxI, creating a positive feedback loop that creates rapid light generation. However, since LuxR negatively regulates ''luxR'', light production is eventually stopped.

''P. aeruginosa'' uses a system similar to LuxI/LuxR . ''lasI'' encodes LasI, which catalyzes formation of a HSL autoinducer(3-oxo-C12-HSL) . 3-oxo-C12-HSL binds to LasR, which regulates a set of genes that include a second QS system, RhlI and RhlR . Because RhlI and RhlR production results from LasR stimulation, it is thought that the two systems are sequential. In addition, 2-heptyl-3-hydroxy-4-quinolone (PQS) is thought to connect the two systems . Both Las and Rhl system regulate various virulence genes important for infection.

Gram positive quorum sensing systems differ from gram negative systems in their autoinducer molecules and how signals are received. Instead of HSL based signals, a peptide is used (called an autoinducing peptide, AIP). These signals cannot diffuse freely like HSL can and are instead transported through ATP-binding protein exporters . In addition, the signal does not directly bind with a transcriptional activator. Instead, it binds to a receptor on the surface of the receiver’s membrane that uses a phosphorylation based relay system to eventually regulate gene expression. Quorum sensing in ''S. pneumonia'' is typical of gram positive bacteria. ''comAB'' encodes for AIP export genes, ''comC'' encodes for the AIP, ''comD'' encodes for response receptor, and ''comE'' encodes for the transcriptional regulator.

Many bacteria have multiple QS systems, as seen with ''P. aeruginosa''. Although autoinducer are usually specific to their receptor, there is sometimes nonspecific signaling or cross-talk between these systems. For example, there is interaction in cystic fibrosis patients between ''P. aeruginosa'' and ''B. cepacia'' . ''B. cepacia'' can recognize the HSL signals produced by P. aeruginosa to activate its ''cep'' QS system, but ''P. aeruginosa'' cannot recognize any of ''B. cepacia’s'' signals. This is important for understanding cystic fibrosis development since ''B. cepacia'' colonizes only after ''P. aeruginosa'' is already established. This suggests that quorum sensing is vital for the development of multispecies communities. Multispecies communication can also be specific. ''luxS'', used to synthesize autoinducer-2 (AI-2), has been found in over 55 species of bacteria and has been found to regulate biofilm development.

It is not necessary for QS systems to function independently. As seen with ''P. aeruginosa'', the Las and Rhl systems are temporally related. Another example is in ''V. harveyi'', in which 3 different signals are used to optimally allow the bacteria to respond depending on the environment. The 3 pathways initially function in parallel, but eventually converge to activate the same result, luminescence .

While quorum sensing is a robust system in the highly variable cellular environment, it is limited by the rate of diffusion and thus is a slow process that constrains the physical size of the system. Communication can also be achieved through gas phase signals, which are relatively faster than diffusion through liquid media, but also are weaker and short lived. Prindle et al. have combined these two signaling methods in order to create "biopixels", a large scale, yet robust quorum sensing system .

==iGEM Connection: MercuroColi==