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Background  Serine/threonine kinases are involved in gene regulation and signal transduction in prokaryotes and eukaryotes. Here, we investigated the role of the serine/threonine kinase Stk in the opportunistic pathogen  Staphylococcus epidermidis .    Methodology/Principal Findings  We constructed an isogenic  stk  mutant of a biofilm-forming clinical  S. epidermidis  isolate. Presence of  stk  was important for biofilm formation  in vitro  and virulence in a murine subcutaneous foreign body infection model. Furthermore, the  stk  mutant exhibited phenotypes indicating an impact of  stk  on metabolic pathways. Using different constructs for the genetic complementation of the  stk  mutant strain with full-length Stk or specific Stk domains, we determined that the Stk intracellular kinase domain is important for biofilm formation and regulation of purine metabolism. Site-specific inactivation of the Stk kinase domain led to defective biofilm formation, in further support of the notion that the kinase activity of Stk regulates biofilm formation of  S. epidermidis . According to immunological detection of the biofilm exopolysaccharide PIA and real-time PCR of the PIA biosynthesis genes, the impact of  stk  on biofilm formation is mediated, at least in part, by a strong influence on PIA expression.    Conclusions  Our study identifies Stk as an important regulator of biofilm formation and virulence of  S. epidermidis , with additional involvement in purine metabolism and the bacterial stress response.

The Eukaryotic-Type Serine/Threonine Protein Kinase Stk Is Required for Biofilm Formation and Virulence in Staphylococcus epidermidis