Quorum Sensing Blocking - the solution
Quorum sensing (QS) is the ability of bacteria to communicate and coordinate behavior via chemical signaling molecules. The purpose of QS is to coordinate certain behavior or actions between bacteria, based on the local density of bacteria. Bacteria that use QS produce and secrete certain signaling molecules (also called autoinducers or quormones). These bacteria also have a receptor that can specifically detect the signaling molecules (QS receptor). When the molecule binds to the receptor, it activates transcription of various genes, including those for signaling molecule synthesis.
Figure 2: Quorum sensing
When the density of bacteria reaches a sufficient level, the concentration of the autoinducer passes a threshold, initiating a positive feedback as more signaling molecule is synthesized, and the receptor becomes fully activated. It induces also the up regulation of other specific genes, for example, various virulence genes like proteases and toxins or the formation of biofilms (Figure 2). Thus in an opportunistic bacterium such as Pseudomonas aeruginosa, QS-related processes include biofilm development, exopolysaccharide production, and cell aggregation. P. aeruginosa can grow within a host without harming it, until they reach a certain population density when they become aggressive, their numbers sufficient to overcome the host's immune system and form a biofilm, leading to disease.
Blocking quorum sensing signalling - “smart microbial control”
While antibiotics and biocides target essential bacterial processes, QuoNova's smart microbial control strategy does not kill organisms but influences their lifestyle.
QuoNova's lead QSB molecules were identified by in silico screening, including flexible alignment on natural signaling molecules, and have since been chemically optimized for different applications. Although they are structurally different from natural QS ligands, data indicate that they interact with the transcriptional receptor with high affinity, resulting in inactivation of the QS blocker-receptor complex.
Disrupting the QS signaling mechanism with QuoNova compounds (Fig 3) keeps bacteria in the planktonic form, even if cell density is high, and renders them harmless (i.e. they do not produce virulence factors) so that they can be removed or controlled more easily by protective mechanisms. QuoNova's QSBs have been demonstrated to have this effect on relevant pathogenic Gram-negative as well as some Gram-positive bacteria.
Figure 3: Quorum Sensing Blocking
Interference with QS affords the great benefit of controlling infectious bacteria without interfering with growth, thus avoiding the type of selection pressure that frequently results in development and selection of bacterial strains resistant to antibiotics. The QuoNova QSBs have also been shown to synergize with antibiotics, potentially permitting the use of much lower doses of antibiotics in the treatment of a broad range of infections, further reducing the selection pressure towards the development of drug resistance.