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

Abstract

Sulfane sulfur, such as inorganic and organic polysulfide (HSn− and RSn−, 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 Cys188 persulfide and trisulfide and produced a pentasulfur link between Cys201 and Cys203. 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, H2O2 inactivates LasR via producing a disulfide bond between Cys201 and Cys203. 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.

Quorum Sensing Promotes Phage Infection in Pseudomonas aeruginosa PAO1

“…Our findings represent an example of evolutionary trade-offs. P. aeruginosa relies on QS to regulate several functions, including the expression of virulence factors and biofilm development ( 11 , 39 ). The virulence factor LPS acts as a phage receptor that is conducive to phage infection, and its synthesis pathway is positively regulated by QS ( Fig.…”

Optimization of a Method for Detecting Intracellular Sulfane Sulfur Levels and Evaluation of Reagents That Affect the Levels in Escherichia coli

“…The iSS level in Pseudomonas aeruginosa is high in the late log phase and early stationary phase of growth, and it activates MexR to turn on the expression of a multiple drug efflux pump MexAB when cells enter the stationary phase [ 10 ]. The high levels of iSS in the late log phase and early stationary phase of growth also significantly enhance the activity of the master quorum-sensing activator LasR in P. aeruginosa [ 11 ]. The multidrug repressor MarR is inactivated by increased iSS in the early stationary phase of growth of E. coli [ 12 ].…”

Lipoic Acid Does Not Affect The Growth of Mycoplasma hominis Cells In Vitro

“…It is known that in bacteria, the concentration of sulfane sulfur can be higher than 100 μM ( Ran et al 2019 ). It has recently been demonstrated that sulfane sulfur increases the virulence in Pseudomonas aeruginosa PAO1 by targeting its quorum sensing (QS) systems ( Xuan et al 2021 ). However, we recall the long known antimicrobial activity of garlic, for which, as we know today, diallyl sulfides are responsible, which are the source of sulfane sulfur.…”