This Article
Right arrow Full Text
Right arrow Full Text (PDF)
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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lührmann, A.
Right arrow Articles by Haas, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lührmann, A.
Right arrow Articles by Haas, A.

 Previous Article  |  Next Article 

Infection and Immunity, February 2004, p. 853-862, Vol. 72, No. 2
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.2.853-862.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Necrotic Death of Rhodococcus equi-Infected Macrophages Is Regulated by Virulence-Associated Plasmids{dagger}

Anja Lührmann,1,2 Norman Mauder,2 Tobias Sydor,1 Eugenia Fernandez-Mora,1,2 Jan Schulze-Luehrmann,1 Shinji Takai,3 and Albert Haas1,2*

Institute for Cell Biology and Bonner Forum Biomedizin, University of Bonn, Bonn,1 Department of Microbiology, Biocenter of the University, Am Hubland, Würzburg, Germany,2 Animal Hygiene, School of Veterinary Medicine and Animal Sciences, Kitasato University, Towada, Aomori, Japan3

Received 14 April 2003/ Returned for modification 2 July 2003/ Accepted 15 October 2003

Rhodococcus equi is a gram-positive intracellular pathogen that can cause severe bronchopneumonia in foals and AIDS patients. It has been reported that advanced infection of foals is characterized by tissue necrosis, coinciding with the presence of degenerate bacteria-laden macrophages. Here, we report that the possession of the VapA-expressing plasmid, which has been previously correlated with a high level of virulence for foals and mice, strongly increases cytotoxicity of R. equi for murine macrophage-like (J774E) cells. Isolates containing different, VapB-expressing plasmids are less virulent and also have a lower cytotoxic potential. Isogenic strains lacking either plasmid are avirulent and have a very low cytotoxic potential. We show, using fluorescence-activated cell sorter analysis (annexin V/7-amino-actinomycin D and sub-G1-analysis), Western blotting [poly(ADP-ribose) polymerase processing analysis], and electron microscopy (macrophage and nucleus morphologies) that the deaths of murine macrophages are the result of necrotic rather than apoptotic events. We demonstrate that the bacteria must be alive in order to act cytotoxic. Therefore, one effect of the virulence-associated plasmids during infection with R. equi is the promotion of necrotic damage to the host.

* Corresponding author. Mailing address: Institute for Cell Biology, University of Bonn, Ulrich-Haberland-Str. 61a, 53121 Bonn, Germany. Phone: 49 228 73 63 40. Fax: 49 228 73 63 04. E-mail: albert.haas{at}uni-bonn.de.

{dagger} A.L., N.M., and T.S. contributed equally to this study.

Editor: S. H. E. Kaufmann

Infection and Immunity, February 2004, p. 853-862, Vol. 72, No. 2
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.2.853-862.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Letek, M., Ocampo-Sosa, A. A., Sanders, M., Fogarty, U., Buckley, T., Leadon, D. P., Gonzalez, P., Scortti, M., Meijer, W. G., Parkhill, J., Bentley, S., Vazquez-Boland, J. A. (2008). Evolution of the Rhodococcus equi vap Pathogenicity Island Seen through Comparison of Host-Associated vapA and vapB Virulence Plasmids. J. Bacteriol. 190: 5797-5805 [Abstract] [Full Text]  
  • Miranda-CasoLuengo, R., Prescott, J. F., Vazquez-Boland, J. A., Meijer, W. G. (2008). The Intracellular Pathogen Rhodococcus equi Produces a Catecholate Siderophore Required for Saprophytic Growth. J. Bacteriol. 190: 1631-1637 [Abstract] [Full Text]  
  • Byrne, G. A., Russell, D. A., Chen, X., Meijer, W. G. (2007). Transcriptional Regulation of the virR Operon of the Intracellular Pathogen Rhodococcus equi. J. Bacteriol. 189: 5082-5089 [Abstract] [Full Text]  
  • Toyooka, K., Takai, S., Kirikae, T. (2005). Rhodococcus equi can survive a phagolysosomal environment in macrophages by suppressing acidification of the phagolysosome. J Med Microbiol 54: 1007-1015 [Abstract] [Full Text]  
  • Wall, D. M., Duffy, P. S., DuPont, C., Prescott, J. F., Meijer, W. G. (2005). Isocitrate Lyase Activity Is Required for Virulence of the Intracellular Pathogen Rhodococcus equi. Infect. Immun. 73: 6736-6741 [Abstract] [Full Text]  


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