title: The auxiliary protein complex SaePQ activates the phosphatase activity of sensor kinase SaeS in the SaeRS two-component system of Staphylococcus aureus.
abstract: In bacterial two-component regulatory systems (TCSs), dephosphorylation of phosphorylated response regulators is essential for resetting the activated systems to the pre-activation state. However, in the SaeRS TCS, a major virulence TCS of Staphylococcus aureus, the mechanism for dephosphorylation of the response regulator SaeR has not been identified. Here we report that two auxiliary proteins from the sae operon, SaeP and SaeQ, form a protein complex with the sensor kinase SaeS and activate the sensor kinase's phosphatase activity. Efficient activation of the phosphatase activity required the presence of both SaeP and SaeQ. When SaeP and SaeQ were ectopically expressed, the expression of coagulase, a sae target with low affinity for phosphorylated SaeR, was greatly reduced, while the expression of alpha-haemolysin, a sae target with high affinity for phosphorylated SaeR, was not, demonstrating a differential effect of SaePQ on sae target gene expression. When expression of SaePQ was abolished, most sae target genes were induced at an elevated level. Since the expression of SaeP and SaeQ is induced by the SaeRS TCS, these results suggest that the SaeRS TCS returns to the pre-activation state by a negative feedback mechanism.
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine-Northwest, Gary, IN 46408, USA.
authors.forename: Do-Won
authors.initials: DW
authors.lastname: Jeong
authors.forename: Hoonsik
authors.initials: H
authors.lastname: Cho
authors.forename: Marcus B
authors.initials: MB
authors.lastname: Jones
authors.forename: Kenneth
authors.initials: K
authors.lastname: Shatzkes
authors.forename: Fei
authors.initials: F
authors.lastname: Sun
authors.forename: Quanjiang
authors.initials: Q
authors.lastname: Ji
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.forename: Scott N
authors.initials: SN
authors.lastname: Peterson
authors.forename: Chuan
authors.initials: C
authors.lastname: He
authors.forename: Taeok
authors.initials: T
authors.lastname: Bae
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013211:Staphylococcus aureus / Q000201:enzymology* / Q000235:genetics; D014157:Transcription Factors
chemical_list: D001426:Bacterial Proteins; C433805:SaeR protein, Staphylococcus aureus; D014157:Transcription Factors; D011494:Protein Kinases; C527351:SaeS protein, Staphylococcus aureus; D010744:Phosphoric Monoester Hydrolases