Therapeutic frontiers: preventing and treating infectious diseases by inhibiting bacterial quorum sensing

Density-dependent cell-cell communication, or quorum sensing (QS), has been demonstrated in numerous species of bacteria. The basic function of QS is likely to confer a nutritional advantage, particularly in a highly populated, mixed-species environment. QS also has ramifications on the production of colonization and virulence factors. Pheromone-like substances secreted into the extracellular milieu appear to govern many of the transcription products in these bacteria. At a high cell density, the QS systems are triggered, and the transcription of the colonization factors are suppressed and replaced by the expression of virulence factors. Major pathogens, such as Pseudomonas aeruginosa and Staphylococcus aureus, have evolved with numerous QS circuits, which modulate the production of various toxins and regulate parallel QS systems. Several QS-modulating therapies, such as macrolide antibiotics, QS vaccines, and competitive QS inhibitors, have been investigated and may prove to be helpful in diminishing the translation of QS-directed toxins or by prematurely activating the QS response to alert the immune system to bacteria hiding in a low cell density. QS represents a recently discovered method of bacterial communication and population control, which may prove to be a unique mechanism to prevent, suppress, and/or treat infectious diseases.