Staphylococcus aureus Trigger Factor Is Involved in Biofilm Formation and Cooperates with the Chaperone PpiB.

Peptidyl-prolyl isomerases (PPIases) are enzymes that assist in protein folding around proline-peptide bonds, and they often possess chaperone activity. encodes three PPIases, i.e., PrsA, PpiB, and trigger factor (TF). Previous work by our group demonstrated a role for both PrsA and PpiB in ; however, TF remains largely unstudied. Here, we identify a role for TF in biofilm formation and demonstrate cooperation between TF and the cytoplasmic PPIase PpiB. Mutation of the gene (encoding TF) led to reduced biofilm development but no significant attenuation of virulence in a mouse model of infection. To investigate whether TF possesses chaperone activity, we analyzed the ability of a mutant to survive acid and base stress. While there was no significant decrease for a mutant, a double mutant exhibited significant decreases in cell viability after acid and base challenges. We then demonstrated that a double mutant had exacerbated phenotypes and , compared to either single mutant. Finally, immunoprecipitation of epitope-tagged PpiB revealed that PpiB interacted with 4 times the number of proteins when TF was absent from the cell, suggesting that it may be compensating for the loss of TF. Interestingly, the only proteins found to interact with TF were TF itself, fibronectin-binding protein B (FnBPB), and the chaperone protein ClpB. Collectively, these results support the first phenotype for TF and demonstrate a greater network of cooperation between chaperone proteins in encodes a large number of virulence factors that aid the bacterium in survival and pathogenesis. These virulence factors have a wide variety of functions; however, they must all be properly secreted in order to be functional. Bacterial chaperone proteins often assist in secretion by trafficking proteins to secretion machinery or assisting in proper protein folding. Here, we report that the chaperone TF contributes to biofilm formation and cooperates with the chaperone PpiB to regulate virulence processes. These data highlight the first known role for TF in and suggest that chaperone proteins may be involved in a greater regulatory network in the cell.