The impact of serine/threonine phosphorylation in Staphylococcus aureus.
In prokaryotes and eukaryotes, phosphotransfer represents a common mechanism to regulate cellular functions. Recent work revealed that modulation of cellular processes by eukaryote-like serine/threonine kinases (STKs) and phosphatases (STPs) are widespread in bacteria. During the last two years, first evidence on the role of Ser/Thr phosphorylation/dephosphorylation in Staphylococcus aureus has emerged leading to the identification of a functional STK and corresponding STP. Due to homology to known STKs/STPs in other bacterial species the kinase was designated PknB or alternatively Stk/Stk1, and the phosphatase Stp. The role of these enzymes in S. aureus has been examined by use of knock-out mutants and a kinase-overexpressing strain. These studies uncovered PknB/Stk and Stp as modulators of cell wall structure and susceptibility to cell wall-acting antibiotics such as certain beta-lactams and tunicamycin. By utilizing transcriptional profile analysis a strong regulatory impact of PknB/Stk on the expression of genes encoding proteins which are involved in purine and pyrimidine biosynthesis, cell wall metabolism, autolysis, and glutamine synthesis could be identified. Moreover, PknB/Stk is able to phosphorylate MgrA, thereby regulating activity of the efflux pump NorA. In a mouse pyelonephritis model PknB/Stk has been shown to play a role in virulence. Overall, Ser/Thr phosphorylation/dephosphorylation is a common theme in regulation of cellular functions determining metabolic activity and virulence also in the major human pathogen S. aureus.
Ohlsen
Knut
K
Institute for Molecular Infection Biology, University of Würzburg, Röntgenring 11, D-97070 Würzburg, Germany. knut.ohlsen@mail.uni-wuerzburg.de
Donat
Stefanie
S
D000818:Animals; D002473:Cell Wall / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D006801:Humans; D053858:Metabolic Networks and Pathways; D051379:Mice; D010749:Phosphoprotein Phosphatases / Q000502:physiology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D013203:Staphylococcal Infections / Q000378:metabolism / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000201:enzymology* / Q000472:pathogenicity; D014774:Virulence; D037521:Virulence Factors / Q000502:physiology*
D037521:Virulence Factors; D017346:Protein Serine-Threonine Kinases; C546823:Stk1 protein, Staphylococcus aureus; D010749:Phosphoprotein Phosphatases