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 VanRheenen, S. M.
Right arrow Articles by Isberg, R. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by VanRheenen, S. M.
Right arrow Articles by Isberg, R. R.

 Previous Article  |  Next Article 

Infection and Immunity, October 2004, p. 5972-5982, Vol. 72, No. 10
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.10.5972-5982.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

IcmF and DotU Are Required for Optimal Effector Translocation and Trafficking of the Legionella pneumophila Vacuole

Susan M. VanRheenen,1 Guillaume Duménil,1,{dagger} and Ralph R. Isberg1,2*

Department of Molecular Biology and Microbiology,1 Howard Hughes Medical Institute, Tufts University Medical School, Boston, Massachusetts2

Received 16 March 2004/ Returned for modification 12 April 2004/ Accepted 1 June 2004

The gram-negative bacterium Legionella pneumophila causes a severe form of pneumonia called Legionnaires' disease, characterized by bacterial replication within alveolar macrophages. Prior to intracellular replication, the vacuole harboring the bacterium must first escape trafficking to the host lysosome, a process that is dependent on the Dot/Icm type IV secretion system. To identify genes required for intracellular growth, bacterial mutants were isolated that were delayed in escape from the macrophage but which retain a minimally functional Dot/Icm machinery. The mutations were found in eight distinct genes, including three genes known to be required for optimal intracellular growth. Two of these genes, icmF and dotU, are located at one end of a cluster of genes that encode the type IV secretion system, yet both icmF and dotU lack orthologs in other type IV translocons. DotU protein is degraded in the early postexponential phase in wild-type L. pneumophila and at all growth phases in an icmF mutant. IcmF contains an extracytoplasmic domain(s) based on accessibility to a membrane-impermeant amine-reactive reagent. In the absence of either gene, L. pneumophila targets inappropriately to LAMP-1-positive compartments during macrophage infection, is defective in the formation of replicative vacuoles, and is impaired in the translocation of the effector protein SidC. Therefore, although IcmF and DotU do not appear to be part of the core type IV secretion system, these proteins are necessary for an efficiently functioning secretion apparatus.

* Corresponding author. Mailing address: Department of Molecular Biology and Microbiology and Howard Hughes Medical Institute, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA 02111. Phone: (617) 636-1392. Fax: (617) 636-0337. E-mail: Ralph.Isberg{at}tufts.edu.

Editor: J. T. Barbieri

{dagger} Present address: INSERM U570, Faculté de Médecine Necker-Enfants Malades, 75015 Paris, France.

Infection and Immunity, October 2004, p. 5972-5982, Vol. 72, No. 10
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.10.5972-5982.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Filloux, A., Hachani, A., Bleves, S. (2008). The bacterial type VI secretion machine: yet another player for protein transport across membranes. Microbiology 154: 1570-1583 [Abstract] [Full Text]  
  • Shalom, G., Shaw, J. G., Thomas, M. S. (2007). In vivo expression technology identifies a type VI secretion system locus in Burkholderia pseudomallei that is induced upon invasion of macrophages. Microbiology 153: 2689-2699 [Abstract] [Full Text]  
  • Liu, Y., Luo, Z.-Q. (2007). The Legionella pneumophila Effector SidJ Is Required for Efficient Recruitment of Endoplasmic Reticulum Proteins to the Bacterial Phagosome. Infect. Immun. 75: 592-603 [Abstract] [Full Text]  
  • Brotcke, A., Weiss, D. S., Kim, C. C., Chain, P., Malfatti, S., Garcia, E., Monack, D. M. (2006). Identification of MglA-Regulated Genes Reveals Novel Virulence Factors in Francisella tularensis. Infect. Immun. 74: 6642-6655 [Abstract] [Full Text]  
  • Mougous, J. D., Cuff, M. E., Raunser, S., Shen, A., Zhou, M., Gifford, C. A., Goodman, A. L., Joachimiak, G., Ordonez, C. L., Lory, S., Walz, T., Joachimiak, A., Mekalanos, J. J. (2006). A virulence locus of Pseudomonas aeruginosa encodes a protein secretion apparatus.. Science 312: 1526-1530 [Abstract] [Full Text]  
  • VanRheenen, S. M., Luo, Z.-Q., O'Connor, T., Isberg, R. R. (2006). Members of a Legionella pneumophila Family of Proteins with ExoU (Phospholipase A) Active Sites Are Translocated to Target Cells.. Infect. Immun. 74: 3597-3606 [Abstract] [Full Text]  
  • Pukatzki, S., Ma, A. T., Sturtevant, D., Krastins, B., Sarracino, D., Nelson, W. C., Heidelberg, J. F., Mekalanos, J. J. (2006). Identification of a conserved bacterial protein secretion system in Vibrio cholerae using the Dictyostelium host model system. Proc. Natl. Acad. Sci. USA 103: 1528-1533 [Abstract] [Full Text]  
  • Miyake, M., Watanabe, T., Koike, H., Molmeret, M., Imai, Y., Abu Kwaik, Y. (2005). Characterization of Legionella pneumophila pmiA, a Gene Essential for Infectivity of Protozoa and Macrophages. Infect. Immun. 73: 6272-6282 [Abstract] [Full Text]  
  • Parsons, D. A., Heffron, F. (2005). sciS, an icmF Homolog in Salmonella enterica Serovar Typhimurium, Limits Intracellular Replication and Decreases Virulence. Infect. Immun. 73: 4338-4345 [Abstract] [Full Text]  
  • Buscher, B. A., Conover, G. M., Miller, J. L., Vogel, S. A., Meyers, S. N., Isberg, R. R., Vogel, J. P. (2005). The DotL Protein, a Member of the TraG-Coupling Protein Family, Is Essential for Viability of Legionella pneumophila Strain Lp02. J. Bacteriol. 187: 2927-2938 [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»