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
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ASM journals
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 McGuffie, E. M.
Right arrow Articles by Olson, J. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McGuffie, E. M.
Right arrow Articles by Olson, J. C.

 Previous Article  |  Next Article 

Infection and Immunity, July 1999, p. 3494-3503, Vol. 67, No. 7
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Differential Sensitivity of Human Epithelial Cells to Pseudomonas aeruginosa Exoenzyme S

Eileen M. McGuffie,1 Jennifer E. Fraylick,2 Debra J. Hazen-Martin,2 Timothy S. Vincent,2 and Joan C. Olson2,*

Department of Experimental Oncology1 and Department of Pathology and Laboratory Medicine,2 Medical University of South Carolina, Charleston, South Carolina 29425

Received 3 February 1999/Returned for modification 15 March 1999/Accepted 12 April 1999

Exoenzyme S (ExoS) is an ADP-ribosyltransferase produced and directly translocated into eukaryotic cells by the opportunistic pathogen Pseudomonas aeruginosa. Model systems that allow bacterial translocation of ExoS have found ExoS to have multiple effects on eukaryotic cell function, affecting DNA synthesis, actin cytoskeletal structure, and cell matrix adherence. To understand mechanisms underlying differences observed in cell sensitivities to ExoS, we examined the effects of bacterially translocated ExoS on multiple human epithelial cell lines. Of the cell lines examined, confluent normal kidney (NK) epithelial cells were most resistant to ExoS, while tumor-derived cell lines were highly sensitive to ExoS. Analysis of the mechanisms of resistance indicated that cell association as well as an intrinsic resistance to morphological alterations were associated with increased resistance to ExoS. Conversely, increased sensitivity to ExoS appeared to be linked to epithelial cell growth, with tumor cells capable of undergoing non-contact-inhibited, anchorage-independent growth all being sensitive to ExoS, and NK cells becoming sensitive to ExoS when subconfluent and growing. Consistent with the possibility that growth-related, actin-based structures are involved in sensitivity to ExoS, scanning electron microscopy revealed cellular extensions from sensitive, growing cells to bacteria, which were not readily evident in resistant cells. In all studies, the severity of effects of ExoS on cell function directly correlated with the degree of Ras modification, indicating that sensitivity to ExoS in some manner related to the efficiency of ExoS translocation and its ADP-ribosylation of Ras. Our results suggest that factors expressed by growing epithelial cells are required for the bacterial contact-dependent translocation of ExoS; as normal epithelial cells differentiate into polarized confluent monolayers, expression of these factors is altered, and cells in turn become more resistant to the effects of ExoS.

* Corresponding author. Mailing address: Medical University of South Carolina, Department of Pathology and Laboratory Medicine, 165 Ashley Ave., Charleston, SC 29425. Phone: (843) 792-7761. Fax: (843) 792-4157. E-mail: olsonj{at}musc.edu.

Infection and Immunity, July 1999, p. 3494-3503, Vol. 67, No. 7
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Bridge, D. R., Novotny, M. J., Moore, E. R., Olson, J. C. (2010). Role of host cell polarity and leading edge properties in Pseudomonas type III secretion. Microbiology 156: 356-373 [Abstract] [Full Text]  
  • Cisz, M., Lee, P.-C., Rietsch, A. (2008). ExoS Controls the Cell Contact-Mediated Switch to Effector Secretion in Pseudomonas aeruginosa. J. Bacteriol. 190: 2726-2738 [Abstract] [Full Text]  
  • O'Grady, E. P., Mulcahy, H., O'Callaghan, J., Adams, C., O'Gara, F. (2006). Pseudomonas aeruginosa Infection of Airway Epithelial Cells Modulates Expression of Kruppel-Like Factors 2 and 6 via RsmA-Mediated Regulation of Type III Exoenzymes S and Y. Infect. Immun. 74: 5893-5902 [Abstract] [Full Text]  
  • Shaver, C. M., Hauser, A. R. (2006). Interactions between effector proteins of the Pseudomonas aeruginosa type III secretion system do not significantly affect several measures of disease severity in mammals. Microbiology 152: 143-152 [Abstract] [Full Text]  
  • Rucks, E. A., Olson, J. C. (2005). Characterization of an ExoS Type III Translocation-Resistant Cell Line. Infect. Immun. 73: 638-643 [Abstract] [Full Text]  
  • Shaver, C. M., Hauser, A. R. (2004). Relative Contributions of Pseudomonas aeruginosa ExoU, ExoS, and ExoT to Virulence in the Lung. Infect. Immun. 72: 6969-6977 [Abstract] [Full Text]  
  • Rucks, E. A., Fraylick, J. E., Brandt, L. M., Vincent, T. S., Olson, J. C. (2003). Cell line differences in bacterially translocated ExoS ADP-ribosyltransferase substrate specificity. Microbiology 149: 319-331 [Abstract] [Full Text]  
  • Fraylick, J. E., La Rocque, J. R., Vincent, T. S., Olson, J. C. (2001). Independent and Coordinate Effects of ADP-Ribosyltransferase and GTPase-Activating Activities of Exoenzyme S on HT-29 Epithelial Cell Function. Infect. Immun. 69: 5318-5328 [Abstract] [Full Text]  
  • Barbieri, A. M., Sha, Q., Bette-Bobillo, P., Stahl, P. D., Vidal, M. (2001). ADP-Ribosylation of Rab5 by ExoS of Pseudomonas aeruginosa Affects Endocytosis. Infect. Immun. 69: 5329-5334 [Abstract] [Full Text]  
  • Ferguson, M. W., Maxwell, J. A., Vincent, T. S., da Silva, J., Olson, J. C. (2001). Comparison of the exoS Gene and Protein Expression in Soil and Clinical Isolates of Pseudomonas aeruginosa. Infect. Immun. 69: 2198-2210 [Abstract] [Full Text]  
  • Kaufman, M. R., Jia, J., Zeng, L., Ha, U., Chow, M., Jin, S. (2000). Pseudomonas aeruginosa mediated apoptosis requires the ADP-ribosylating activity of ExoS. Microbiology 146: 2531-2541 [Abstract] [Full Text]  
  • Dacheux, D., Toussaint, B., Richard, M., Brochier, G., Croize, J., Attree, I. (2000). Pseudomonas aeruginosa Cystic Fibrosis Isolates Induce Rapid, Type III Secretion-Dependent, but ExoU-Independent, Oncosis of Macrophages and Polymorphonuclear Neutrophils. Infect. Immun. 68: 2916-2924 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»