Spx is a global effector impacting stress tolerance and biofilm formation in Staphylococcus aureus

In Bacillus subtilis, Spx was recently characterized as a novel type of global regulator whose activity is regulated by the redox status of the cells. In the present study, we demonstrate that inactivation of Spx in the important pathogen Staphylococcus aureus renders the cells hypersensitive to a wide range of stress conditions including high and low temperature, high osmolarity, and hydrogen peroxide. Moreover, growth was restricted under nonstress conditions. Two-dimensional gel electrophoresis revealed that the proteome of the spx mutant differs substantially from the proteome of wild-type cells, supporting the finding that Spx is also a global regulator in S. aureus. More specifically, we demonstrated that Spx is required for transcription of trxB, encoding thioredoxin reductase, under all growth conditions examined. As trxB is essential in S. aureus, we speculate that the severely reduced trxB transcription could account for some of the growth defects of the spx mutant. Inactivation of spx also enhanced biofilm formation. S. aureus biofillm formation is associated with the production of the polysaccharide intercellular adhesin encoded by the ica operon. Interestingly, our data indicate that the augmented capacity of the spx mutant to form biofilms is due to Spx modulating the expression of icaR, encoding a repressor of the structural ica genes (icaABCD). In summary, we conclude that Spx fulfills an important role for growth, general stress protection, and biofilm formation in S. aureus.