Characterization of a Serine/Threonine Kinase Involved in Virulence of Staphylococcus aureus

• DOI: 10.1128/jb.01813-08
• Publication Date: 2009-04-25T00:46:55Z
• Authors: Michel Débarboui...; Shaynoor Dramsi; Olivier Dussurget; Marie-Anne Nahori; Elisabeth Vaganay; Grégory Jouvion; Alain Cozzone; Tarek Msadek; Bertrand Duclos
• Keywords: 0301 basic medicine; [SDV]Life Sciences [q-bio]; MESH: Virulence; [SHS]Humanities and Social Sciences; MESH: Protein Structure, Tertiary; Mice; MESH: Fosfomycin; MESH: Staphylococcus aureus; Site-Directed; MESH: Animals; MESH: Bacterial Proteins; MESH: Mutagenesis; MESH: Genetic Complementation Test; MESH: Immunoblotting; Virulence; Staphylococcal Infections; 3. Good health; [SDV] Life Sciences [q-bio]; MESH: Mutagenesis, Site-Directed; [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology; Female; [SHS] Humanities and Social Sciences; MESH: Operon; Staphylococcus aureus; MESH: Mutation; 572; Octoxynol; Immunoblotting; MESH: Staphylococcal Infections; MESH: Manganese; Protein Serine-Threonine Kinases; MESH: Protein-Serine-Threonine Kinases; 03 medical and health sciences; Bacterial Proteins; Fosfomycin; MESH: Octoxynol; Operon; Animals; MESH: Mice; [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology; Manganese; Cell Membrane; Genetic Complementation Test; Protein Structure, Tertiary; MESH: Protein Structure; Mutation; Mutagenesis, Site-Directed; MESH: Female; Tertiary; MESH: Cell Membrane

Staphylococcus aureus is a common human cutaneous and nasal commensal major life-threatening pathogen. Adaptation to the different environments encountered inside outside host crucial requirement for survival colonization. We identified characterized eukaryotic-like serine/threonine kinase with three predicted extracellular PASTA domains (SA1063, or Stk1) its associated phosphatase (SA1062, Stp1) in S. aureus. Biochemical analyses revealed that Stk1 displays autokinase activity on threonine serine residues localized membrane. Stp1 cytoplasmic protein manganese-dependent toward phosphorylated Stk1. In-frame deletions of stk1 stp1 genes were constructed strain 8325-4. Phenotypic mutants reduced growth mutant RPMI 1640 defined medium was restored when adenine added medium. Furthermore, displayed increased resistance Triton X-100 fosfomycin, suggesting modifications cell wall metabolism. The tested virulence mouse pyelonephritis model found be strongly kidneys (approximately 2-log-unit decrease) compared parental strain. Renal histopathological showed severe inflammatory lesions mice infected SH1000 strain, whereas Deltastk1 led only minimal renal lesions. These results confirm important role full expression pathogenesis suggest phosphorylation levels controlled by are essential controlling bacterial within host.