D-118. A Staphylococcal Eukaryotic-Like Serine/Threonine Kinase and Phosphatase Are Implicated in Antimicrobial Resistance and Adhesion

A. M. Beltramini, V. Pancholi;
The Ohio State Univ., Columbus, OH.

Reversible phosphorylation carried out by serine/threonine kinases (STKs) and phosphatases (STPs) is a key mechanism by which eukaryotes regulate their cellular functions. Although the mechanisms by which eukaryotic-type STKs and STPs regulate certain functions in prokaryotes is not yet well established, many studies have recently indicated that these enzymes are not only present in prokaryotes but also play a crucial role in bacterial morphology and pathogenesis. So far, the role of these enzymes in the pathogenesis of Staphylococcus aureus is not known. We hypothesize, based on the role of STKs and STPs in other Gram-positive organisms, that STKs and STPs are required for proper execution of resistance and adhesion mechanisms in S. aureus. In this study, we have identified a major eukaryotic-like serine/threonine kinase (sauSTK) and phosphatase (sauSTP) in S. aureus and investigated their involvement in antimicrobial resistance, and biofilm formation. By utilizing gene knock out strategies, we created two S. aureus mutant strains lacking either STK alone or both STK and STP. S. aureus mutants lacking both STK and STP displayed significantly increased susceptibility to third generation cephalosporins and ertapenem as well as a reduced ability to adhere to polystyrene, as compared to wild type. Similarly, mutants lacking STK alone displayed moderately increased susceptibility to third generation cephalosporins and ertapenem but, in contrast to mutants lacking both STK and STP, displayed enhanced adhesion to polystyrene and resistance to lysostaphin as compared to wild type. These results conclude that sauSTK and sauSTP play an important role in staphylococcal pathogenesis by directly or indirectly regulating these cellular processes. Staphylococcal sauSTK and sauSTP may thus serve as important antibiotic targets for multidrug-resistant S. aureus.