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Originally published In Press as doi:10.1074/jbc.M606249200 on August 11, 2006

J. Biol. Chem., Vol. 281, Issue 42, 31812-31822, October 20, 2006
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Control of Listeria Superoxide Dismutase by Phosphorylation*Formula

Cristel Archambaud1, Marie-Anne Nahori, Javier Pizarro-Cerda, Pascale Cossart2, and Olivier Dussurget3

From the Institut Pasteur, Unité des Interactions Bactéries-Cellules, Inserm, U604, INRA, USC2020, F-75015 Paris, France

Superoxide dismutases (SODs) are enzymes that protect organisms against superoxides and reactive oxygen species (ROS) produced during their active metabolism. ROS are major mediators of phagocytes microbicidal activity. Here we show that the cytoplasmic Listeria monocytogenes MnSOD is phosphorylated on serine and threonine residues and less active when bacteria reach the stationary phase. We also provide evidence that the most active nonphosphorylated form of MnSOD can be secreted via the SecA2 pathway in culture supernatants and in infected cells, where it becomes phosphorylated. A {Delta}sod deletion mutant is impaired in survival within macrophages and is dramatically attenuated in mice. Together, our results demonstrate that the capacity to counteract ROS is an essential component of L. monocytogenes virulence. This is the first example of a bacterial SOD post-translationally controlled by phosphorylation, suggesting a possible new host innate mechanism to counteract a virulence factor.


Received for publication, June 29, 2006 , and in revised form, July 27, 2006.

* This work was supported in part from Institut Pasteur (GPH N°9); INRA, INSERM, and the French Ministry of Research (Programme de Microbiologie Fondamentale et Appliquée, Maladies Infectieuses, Environment et Bioterrorisme ACI N° MIC 0312). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Formula The on-line version of this article (available at http://www.jbc.org) contains two supplemental experimental procedures, one supplemental Table S1, and four supplemental Figs. S1-S4.

1 Supported by fellowships from the Ministère de la Recherche, the Pasteur-Weizmann Foundation, EuroPathoGenomics (NoE, Contract N° LSHB-CT-2005-512061) and the Howard Hughes Medical Institute.

2 An International Research Scholar of the Howard Hughes Medical Institute. To whom correspondence may be addressed. Tel.: 33-1-40-61-30-32; Fax: 33-1-45-68-87-06; E-mail: pcossart{at}pasteur.fr.

3 To whom correspondence may be addressed: Unité des Interactions Bactéries-Cellules, Institut Pasteur, 25 rue du Dr. Roux, 75015 Paris, France. E-mail: odussur{at}pasteur.fr.


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