Sulfane Sulfur Regulates LasR-Mediated Quorum Sensing and Virulence in Pseudomonas aeruginosa PAO1

Sulfane sulfur, such as inorganic and organic polysulfide (HS(n)(−) and RS(n)(−), n > 2), is a common cellular component, produced either from hydrogen sulfide oxidation or cysteine metabolism. In Pseudomonas aeruginosa PAO1, LasR is a quorum sensing master regulator. After binding its autoinducer, LasR binds to its target DNA to activate the transcription of a suite of genes, including virulence factors. Herein, we report that the production of hydrogen sulfide and sulfane sulfur were positively correlated in P. aeruginosa PAO1, and sulfane sulfur was able to modify LasR, which generated Cys(188) persulfide and trisulfide and produced a pentasulfur link between Cys(201) and Cys(203). The modifications did not affect LasR binding to its target DNA site, but made it several-fold more effective than unmodified LasR in activating transcription in both in vitro and in vivo assays. On the contrary, H(2)O(2) inactivates LasR via producing a disulfide bond between Cys(201) and Cys(203). P. aeruginosa PAO1 had a high cellular sulfane sulfur and high LasR activity in the mid log phase and early stationary phase, but a low sulfane sulfur and low LasR activity in the declination phase. Thus, sulfane sulfur is a new signaling factor in the bacterium, adding another level of control over LasR-mediated quorum sensing and turning down the activity in old cells.