Abstract
BackgroundBacteria release a wide variety of small molecules including cell-to-cell signaling compounds. Gram-negative bacteria use a variety of self-produced autoinducers such as acylated homoserine lactones (acyl-HSLs) as signal compounds for quorum sensing (QS) within and between bacterial species. QS plays a significant role in the pathogenesis of infectious diseases and in beneficial symbiosis by responding to acyl-HSLs in Pseudomonas aeruginosa. It is considered that the selection of bacterial languages is necessary to regulate gene expression and thus it leads to the regulation of virulence and provides a growth advantage in several environments. In this study, we hypothesized that RND-type efflux pump system MexAB-OprM of P. aeruginosa might function in the selection of acyl-HSLs, and we provide evidence to support this hypothesis.ResultsLoss of MexAB-OprM due to deletion of mexB caused increases in QS responses, as shown by the expression of gfp located downstream of the lasB promoter and LasB elastase activity, which is regulated by a LasR-3-oxo-C12-HSL complex. Either complementation with a plasmid containing wild-type mexB or the addition of a LasR-specific inhibitor, patulin, repressed these high responses to 3-oxo-acyl-HSLs. Furthermore, it was shown that the acyl-HSLs-dependent response of P. aeruginosa was affected by the inhibition of MexB transport activity and the mexB mutant. The P. aeruginosa MexAB-OprM deletion mutant showed a strong QS response to 3-oxo-C10-HSL produced by Vibrio anguillarum in a bacterial cross-talk experiment.ConclusionThis work demonstrated that MexAB-OprM does not control the binding of LasR to 3-oxo-Cn-HSLs but rather accessibility of non-cognate acyl-HSLs to LasR in P. aeruginosa. MexAB-OprM not only influences multidrug resistance, but also selects acyl-HSLs and regulates QS in P. aeruginosa. The results demonstrate a new QS regulation mechanism via the efflux system MexAB-OprM in P. aeruginosa.
Highlights
Bacteria release a wide variety of small molecules including cell-to-cell signaling compounds
The results demonstrate a new quorum sensing (QS) regulation mechanism via the efflux system MexAB-OprM in P. aeruginosa
MexAB-OprM selects acyl-HSLs and regulates quorum sensing To determine whether or not the expression of the QS regulatory pathway in P. aeruginosa is influenced by exogenous acyl-HSLs substituted with 3-oxo-acyl groups with carbon numbers of 6 to 14, lasB transcription was measured by using a lasB promoter-gfp reporter system
Summary
Bacteria release a wide variety of small molecules including cell-to-cell signaling compounds. Gramnegative bacteria use a variety of self-produced autoinducers such as acylated homoserine lactones (acyl-HSLs) as signal compounds for quorum sensing (QS) within and between bacterial species. It is considered that the selection of bacterial languages is necessary to regulate gene expression and it leads to the regulation of virulence and provides a growth advantage in several environments. Gram-negative bacteria use a variety of self-produced autoinducers such as acylated homoserine lactones as a language for quorum sensing (QS) within and between bacterial species. It. The opportunistic bacterium P. aeruginosa is widespread in various environments and utilizes two acyl-HSL signaling molecules, N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12-HSL), and N-butanoyl-L-homoserine lactone (C4-HSL), and two receptor proteins, LasR and RhlR, respectively [3]. A specific response to an autoinducer is important to determine the virulence of P. aeruginosa
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