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

Abstract

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.

Pseudomonas aeruginosa Directly Shunts β-Oxidation Degradation Intermediates into De Novo Fatty Acid Biosynthesis

“…Fatty acid metabolism in especially complex in pseudomonads, with an unusually large genetic allocation to both the catabolism and anabolism of fatty acids (32,50,51). To further confirm the two activities of PA3286 observed in P. aeruginosa PAO1, to probe the substrate specificity and to determine whether PA3286 requires partner proteins for intercepting ␤-oxidation cycle intermediates, we introduced the PA3286 gene into the model E. coli strain BW25113.…”

“…syringae B728a (black); PFLU, P. fluorescens SBW25 (black); Avin, Azotobacter vinelandii DJ (purple); b, E. coli (green). tion of iron acquisition by blocking siderophore production (53), and QS inhibition in particular (50), have garnered substantial interest as strategies for treating P. aeruginosa infections. The three dominant QS signal molecules from the las, rhl, and PQS systems, all of which contain fatty acid moieties, together form a complex, cell density-dependent regulatory circuit controlling the expression of a suite of virulence factors (87,89).…”

The quorum-quenching N -acyl homoserine lactone acylase PvdQ is an Ntn-hydrolase with an unusual substrate-binding pocket

“…Furthermore, it has been shown that the interruption of bacterial communication by quorum quenching can prevent pathogens from displaying virulent behavior (7). Therefore, quorum quenching could be used in the development of new antimicrobial strategies because many pathogens depend on quorum sensing in regulating virulence (6,8).…”

Anti-quorum sensing and antimicrobial activities of some traditional Chinese medicinal plants commonly used in South-East Asia

“…It appears there may be that more than one compound present in the ginseng extract, one of which is an agonist of swarming, with others that may affect a different signalling pathway in Pseudomonas aeruginosa PAO1, stimulating pyocyanin synthesis. Indeed, major pathogens such as P. aeruginosa, have evolved with numerous QS circuits, which modulate the production of various toxins and regulate parallel QS systems (Martin et al, 2008). Swarming motility in itself is a complex phenotype that involves several other traits (Overhage et …”