Figure 1.

Schematic representation of the synthesis of QSSMs and their relationship with RND efflux activity in P. aeruginosa. Previous studies have shown that MexAB-OprM, MexCD-OprJ, and MexEF-OprN are efflux system able to extrude QS-related compounds, a feature that produces an impaired QS response and virulence factors production. Therefore, the overexpression of MexAB-OprM has been associated with an impaired production (not extrusion) of one of the immediate precursors of HHQ, octanoic acid, rather than with a nonphysiological extrusion of 3-oxo-C12-HSL as was initially stated [24,48]. In our work, we suggested that this lower availability of octanoic acid is probably due to the efflux of some of the intermediates in fatty acid metabolism that function as precursors of octanoate synthesis. With respect to MexCD-OprJ and MexEF-OprN, both of them are able to efflux HHQ and the AQs precursor kynurenine [23,25,49], but with different efficiency, being the extrusion of either HHQ or kynurenine most relevant in mutants that overexpress MexCD-OprJ or MexEF-OprN, respectively. Some other studies have also associated the activity of the MexGHI-OpmD efflux system with the QS network at two different levels: (i) extruding anthranilate, which is the other one immediate precursor of HHQ [26], and (ii) extruding 5-Me-PCA, the immediate precursor of pyocyanin, a QS-controlled virulence factor that in turns drives the expression of some other QS-related genes [50]. Altogether, these results support that RND efflux systems are a key element in the modulation of the QS response at different levels [19,20].