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Journal of Bacteriology, July 2009, p. 4070-4081, Vol. 191, No. 13
0021-9193/09/$08.00+0     doi:10.1128/JB.01813-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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

Michel Débarbouillé,1,2,§ Shaynoor Dramsi,1,2,§ Olivier Dussurget,3,4,5 Marie-Anne Nahori,3,4,5 Elisabeth Vaganay,6 Grégory Jouvion,7 Alain Cozzone,6 Tarek Msadek,1,2* and Bertrand Duclos6

Institut Pasteur, Unité de Biologie des Bactéries Pathogènes à Gram Positif,1 CNRS URA 2172, 25 rue du Docteur Roux—75724 Paris Cedex 15, France,2 Institut Pasteur, Unité des Interactions Bactéries-Cellules,3 Inserm U604,4 INRA USC2020, 25 rue du Docteur Roux—75724 Paris Cedex 15, France,5 Unité Mixte de Recherche 5086—CNRS/Université de Lyon, Institut de Biologie et Chimie des Protéines, Lyon, France,6 Institut Pasteur, Unité de Recherche et d'Expertise Histotechnologie et Pathologie, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France7

Received 23 December 2008/ Accepted 6 April 2009

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

* Corresponding author. Mailing address: Institut Pasteur, Unité de Biologie des Bactéries Pathogènes à Gram Positif, 25 rue du Docteur Roux—75724 Paris Cedex 15, France. Phone: (33) 1 45 68 88 09. Fax: (33) 1 45 68 89 38. E-mail: tmsadek{at}pasteur.fr

{triangledown} Published ahead of print on 24 April 2009.

§ M.D. and S.D. contributed equally to this work.

Journal of Bacteriology, July 2009, p. 4070-4081, Vol. 191, No. 13
0021-9193/09/$08.00+0     doi:10.1128/JB.01813-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Donat, S., Streker, K., Schirmeister, T., Rakette, S., Stehle, T., Liebeke, M., Lalk, M., Ohlsen, K. (2009). Transcriptome and Functional Analysis of the Eukaryotic-Type Serine/Threonine Kinase PknB in Staphylococcus aureus. J. Bacteriol. 191: 4056-4069 [Abstract] [Full Text]  


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