However, a number of interesting variations have since been described in the AHL synthesis/AHL response gene layout and regulation of the QS genes. The goal of this work is to show, based on a new survey of the genomic databases, how these HTS variations correlate with the topological arrangement of the QS regulatory genes.2.?A Generalized Regulatory Framework of N-AHL-Based Quorum SensingIn general terms, N-AHL-based QS signaling is often referred to as mere autoinduction, requiring only a synthase and a sensor/regulator protein. However, in the absence of regulation of QS, autoinduction would increase signal levels without limit. A down-regulation loop (Figure 1), which turns on at higher signal concentrations is the simplest way to limit and stabilize the signal levels.
There are a variety of mechanisms that can play this role in QS systems. For example, the master regulator TraM can form a non-functional heterodimer with the TraR regulator in Agrobacterium tumefaciens Inhibitors,Modulators,Libraries [18,19]. The DNA-binding negative regulator RsaL acts as a homo-dimer by binding on the bi-directional rsaL-luxI promoter [20]. RsaM is another small regulatory protein believed to be acting in a similar way to RsaL in many Burkholderia species [21]. The crucial role of these negative regulators is highlighted by the fact that their deletion leads to signal overproduction and a less virulent bacterial phenotype. Bacterial genomes Inhibitors,Modulators,Libraries also encode enzymes that degrade AHLs in response to the stress signal ppGpp, which can also efficiently down-regulate QS signaling [22,23]. Down-regulation can also be achieved by RNA-based mechanisms.
For example, some QS systems act by activating in their ground state an RNA-binding protein that inhibits Inhibitors,Modulators,Libraries transcription of synthases, and then gradually removing the inhibition when signal concentrations are increased [24,25]. Meanwhile, another class of QS regulation system is believed to use sRNA species that considerably decrease the mRNA of the LuxR genes at low population density [26�C28]. For the sake of completeness we mention Inhibitors,Modulators,Libraries that downregulation can also be achieved by simple resource limitation where a reduction in number of QS cells would decrease of the QS signal concentration itself.Figure 1.Regulatory outline of N-AHL-based QS signaling. Pointed arrows indicate activation, and the hammerhead arrow indicates inhibition.
Regulatory circuits in which an element can both activate and inhibit another element are termed incoherent feed forward loops (IFFLs) [29,30]. In contrast to simple feed forward arrangements, IFFLs can exhibit a number of complex behavior patterns AV-951 (for a review see [31]). While simple feed forward circuits have no inherent limits on their output, IFFL networks have bounded output, selleck chemical Rucaparib which ensures robustness against fluctuations in the input signal levels.