This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Rolando, M.
Right arrow Articles by Lemichez, E.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rolando, M.
Right arrow Articles by Lemichez, E.

 Previous Article  |  Next Article 

Infection and Immunity, September 2009, p. 3596-3601, Vol. 77, No. 9
0019-9567/09/$08.00+0     doi:10.1128/IAI.00186-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Injection of Staphylococcus aureus EDIN by the Bacillus anthracis Protective Antigen Machinery Induces Vascular Permeability{triangledown} ,{dagger}

Monica Rolando,1,2 Patrick Munro,1,2 Caroline Stefani,1,2 Patrick Auberger,1,2,3 Gilles Flatau,1,2 and Emmanuel Lemichez1,2,4*

INSERM, U895, Equipe 6, C3M, Microbial Toxins in Host Pathogen Interactions, Nice F-06204, France,1 Université de Nice-Sophia-Antipolis, UFR Médecine, IFR50, Nice F-06204, France,2 INSERM, U895, Equipe 2, C3M, Mort cellulaire, differentiation et cancer, Nice F-06107, France,3 Centre Hospitalier Universitaire de Nice, Hôpital l'Archet, Laboratoire de Bactériologie, Nice F-06204, France4

Received 18 February 2009/ Returned for modification 8 April 2009/ Accepted 28 May 2009

Systemic injection of Bacillus anthracis lethal toxin (LT) produces vascular leakage and animal death. Recent studies suggest that LT triggers direct endothelial cell cytotoxicity that is responsible for the vascular leakage. LT is composed of heptamers of protective antigen (PA), which drives the endocytosis and translocation into host cells of the lethal factor (LF), a mitogen-activated protein kinase kinase protease. Here we investigated the consequences of injection of an endothelium-permeabilizing factor using LT as a "molecular syringe." To this end, we generated the chimeric factor LE, corresponding to the PA-binding domain of LF (LF1-254) fused to EDIN exoenzyme. EDIN ADP ribosylates RhoA, leading to actin cable disruption and formation of transcellular tunnels in endothelial cells. We report that systemic injection of LET (LE plus PA) triggers a PA-dependent increase in the pulmonary endothelium permeability. We also report that native LT induces a progressive loss of endothelium barrier function. We established that there is a direct correlation between the extent of endothelium permeability induced by LT and the cytotoxic activity of LT. This suggests new ways to design therapeutic drugs against anthrax directed toward vascular permeability.

* Corresponding author. Mailing address: Bâtiment Universitaire Archimed, INSERM, U895, Equipe 6, C3M, 151 Route de Saint Antoine de Ginestière, BP 2 3194, F-06204 Nice Cedex 3, France. Phone: 00 33 (0)4 89 06 42 63. Fax: 00 33 (0)4 89 06 42 60. E-mail: lemichez{at}unice.fr

{triangledown} Published ahead of print on 22 June 2009.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: S. R. Blanke

Infection and Immunity, September 2009, p. 3596-3601, Vol. 77, No. 9
0019-9567/09/$08.00+0     doi:10.1128/IAI.00186-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»