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 Glomski, I. J.
Right arrow Articles by Portnoy, D. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Glomski, I. J.
Right arrow Articles by Portnoy, D. A.

 Previous Article  |  Next Article 

Infection and Immunity, December 2003, p. 6754-6765, Vol. 71, No. 12
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.12.6754-6765.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Listeria monocytogenes Mutants That Fail To Compartmentalize Listerolysin O Activity Are Cytotoxic, Avirulent, and Unable To Evade Host Extracellular Defenses

Ian J. Glomski,1 Amy L. Decatur,1,{dagger} and Daniel A. Portnoy1,2*

Department of Molecular and Cell Biology,1 The School of Public Health, University of California, Berkeley, California 94720-32022

Received 12 August 2003/ Accepted 4 September 2003

Listeria monocytogenes is a facultative intracellular bacterial pathogen that escapes from a phagosome and grows in the host cell cytosol. Escape of the bacterium from the phagosome to the cytosol is mediated by the bacterial pore-forming protein listeriolysin O (LLO). LLO has multiple mechanisms that optimize activity in the phagosome and minimize activity in the host cytosol. Mutants that fail to compartmentalize LLO activity are cytotoxic and have reduced virulence. We sought to determine why cytotoxic bacteria have attenuated virulence in the mouse model of listeriosis. In this study, we constructed a series of strains with mutations in LLO and with various degrees of cytotoxicity. We found that the more cytotoxic the strain in cell culture, the less virulent it was in mice. Induction of neutropenia increased the relative virulence of the cytotoxic strains 100-fold in the spleen and 10-fold in the liver. The virulence defect was partially restored in neutropenic mice by adding gentamicin, an antibiotic that kills extracellular bacteria. Additionally, L. monocytogenes grew more slowly in extracellular fluid (mouse serum) than within tissue culture cells. We concluded that L. monocytogenes controls the cytolytic activity of LLO to maintain its nutritionally rich intracellular niche and avoid extracellular defenses of the host.

* Corresponding author. Mailing address: Department of Molecular and Cell Biology, 401 Barker Hall, University of California, Berkeley, Berkeley, California 94703-3200. Phone: (510) 643-3925. Fax: (510) 643-6791. E-mail: portnoy{at}uclink4.berkeley.edu.

Editor: V. J. DiRita

{dagger} Present address: Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6076.

Infection and Immunity, December 2003, p. 6754-6765, Vol. 71, No. 12
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.12.6754-6765.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Carrero, J. A., Calderon, B., Vivanco-Cid, H., Unanue, E. R. (2009). Recombinant Listeria monocytogenes Expressing a Cell Wall-Associated Listeriolysin O Is Weakly Virulent but Immunogenic. Infect. Immun. 77: 4371-4382 [Abstract] [Full Text]  
  • Alonzo, F. III, Port, G. C., Cao, M., Freitag, N. E. (2009). The Posttranslocation Chaperone PrsA2 Contributes to Multiple Facets of Listeria monocytogenes Pathogenesis. Infect. Immun. 77: 2612-2623 [Abstract] [Full Text]  
  • Zemansky, J., Kline, B. C., Woodward, J. J., Leber, J. H., Marquis, H., Portnoy, D. A. (2009). Development of a mariner-Based Transposon and Identification of Listeria monocytogenes Determinants, Including the Peptidyl-Prolyl Isomerase PrsA2, That Contribute to Its Hemolytic Phenotype. J. Bacteriol. 191: 3950-3964 [Abstract] [Full Text]  
  • Lauer, P., Hanson, B., Lemmens, E. E., Liu, W., Luckett, W. S., Leong, M. L., Allen, H. E., Skoble, J., Bahjat, K. S., Freitag, N. E., Brockstedt, D. G., Dubensky, T. W. Jr. (2008). Constitutive Activation of the PrfA Regulon Enhances the Potency of Vaccines Based on Live-Attenuated and Killed but Metabolically Active Listeria monocytogenes Strains. Infect. Immun. 76: 3742-3753 [Abstract] [Full Text]  
  • Schnupf, P., Zhou, J., Varshavsky, A., Portnoy, D. A. (2007). Listeriolysin O Secreted by Listeria monocytogenes into the Host Cell Cytosol Is Degraded by the N-End Rule Pathway. Infect. Immun. 75: 5135-5147 [Abstract] [Full Text]  
  • Hamon, M. A., Batsche, E., Regnault, B., Tham, T. N., Seveau, S., Muchardt, C., Cossart, P. (2007). Histone modifications induced by a family of bacterial toxins. Proc. Natl. Acad. Sci. USA 104: 13467-13472 [Abstract] [Full Text]  
  • Nomura, T., Kawamura, I., Kohda, C., Baba, H., Ito, Y., Kimoto, T., Watanabe, I., Mitsuyama, M. (2007). Irreversible loss of membrane-binding activity of Listeria-derived cytolysins in non-acidic conditions: a distinct difference from allied cytolysins produced by other Gram-positive bacteria. Microbiology 153: 2250-2258 [Abstract] [Full Text]  
  • Yeung, P. S. M., Na, Y., Kreuder, A. J., Marquis, H. (2007). Compartmentalization of the Broad-Range Phospholipase C Activity to the Spreading Vacuole Is Critical for Listeria monocytogenes Virulence. Infect. Immun. 75: 44-51 [Abstract] [Full Text]  
  • Lety, M.-A., Frehel, C., Raynaud, C., Dupuis, M., Charbit, A. (2006). Exploring the role of the CTL epitope region of listeriolysin O in the pathogenesis of Listeria monocytogenes.. Microbiology 152: 1287-1296 [Abstract] [Full Text]  
  • Cerro-Vadillo, E. d., Madrazo-Toca, F., Carrasco-Marin, E., Fernandez-Prieto, L., Beck, C., Leyva-Cobian, F., Saftig, P., Alvarez-Dominguez, C. (2006). Cutting Edge: A Novel Nonoxidative Phagosomal Mechanism Exerted by Cathepsin-D Controls Listeria monocytogenes Intracellular Growth. J. Immunol. 176: 1321-1325 [Abstract] [Full Text]  
  • Yoshimura, K., Jain, A., Allen, H. E., Laird, L. S., Chia, C. Y., Ravi, S., Brockstedt, D. G., Giedlin, M. A., Bahjat, K. S., Leong, M. L., Slansky, J. E., Cook, D. N., Dubensky, T. W., Pardoll, D. M., Schulick, R. D. (2006). Selective Targeting of Antitumor Immune Responses with Engineered Live-Attenuated Listeria monocytogenes. Cancer Res. 66: 1096-1104 [Abstract] [Full Text]  
  • Wei, Z., Schnupf, P., Poussin, M. A., Zenewicz, L. A., Shen, H., Goldfine, H. (2005). Characterization of Listeria monocytogenes Expressing Anthrolysin O and Phosphatidylinositol-Specific Phospholipase C from Bacillus anthracis. Infect. Immun. 73: 6639-6646 [Abstract] [Full Text]  
  • Cheng, L. W., Viala, J. P. M., Stuurman, N., Wiedemann, U., Vale, R. D., Portnoy, D. A. (2005). Use of RNA interference in Drosophila S2 cells to identify host pathways controlling compartmentalization of an intracellular pathogen. Proc. Natl. Acad. Sci. USA 102: 13646-13651 [Abstract] [Full Text]  
  • Vance, R. E., Rietsch, A., Mekalanos, J. J. (2005). Role of the Type III Secreted Exoenzymes S, T, and Y in Systemic Spread of Pseudomonas aeruginosa PAO1 In Vivo. Infect. Immun. 73: 1706-1713 [Abstract] [Full Text]  
  • O'Brien, D. K., Melville, S. B. (2004). Effects of Clostridium perfringens Alpha-Toxin (PLC) and Perfringolysin O (PFO) on Cytotoxicity to Macrophages, on Escape from the Phagosomes of Macrophages, and on Persistence of C. perfringens in Host Tissues. Infect. Immun. 72: 5204-5215 [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»