Journal article
Interruption of Multiple Cellular Processes in HT-29 Epithelial Cells by Pseudomonas aeruginosa Exoenzyme S
Infection and immunity, Vol.67(6), pp.2847-2854
06/1999
DOI: 10.1128/IAI.67.6.2847-2854.1999
PMCID: PMC96591
PMID: 10338490
Abstract
Exoenzyme S (ExoS), an ADP-ribosylating enzyme produced by the opportunistic pathogen
Pseudomonas aeruginosa
, is directly translocated into eukaryotic cells by bacterial contact. Within the cell, ExoS ADP-ribosylates the cell signaling protein Ras and causes inhibition of DNA synthesis and alterations in cytoskeletal structure. To further understand the interrelationship of the different cellular effects of ExoS, functional analyses were performed on HT-29 epithelial cells after exposure to ExoS-producing
P. aeruginosa
388 and the non-ExoS-producing strain 388ΔS. Two different mechanisms of morphological alteration were identified: (i) a more-transient and less-severe cell rounding caused by the non-ExoS-producing strain 388ΔS and (ii) a more-severe, long-term cell rounding caused by ExoS-producing strain 388. Long-term effects of ExoS on cell morphology occurred in conjunction with ExoS-mediated inhibition of DNA synthesis and the ADP-ribosylation of Ras. ExoS was also found to cause alterations in HT-29 cell function, leading to the loss of cell adhesion and microvillus effacement. Nonadherent ExoS-treated cells remained viable but had a high proportion of modified Ras. While microvillus effacement was detected in both 388- and 388ΔS-treated cells, effacement was more prevalent and rapid in cells exposed to strain 388. We conclude from these studies that ExoS can have multiple effects on epithelial cell function, with more severe cellular alterations associated with the enzymatic modification of Ras. The finding that ExoS had greater effects on cell growth and adherence than on cell viability suggests that ExoS may contribute to the
P. aeruginosa
infectious process by rendering cells nonfunctional.
Details
- Title: Subtitle
- Interruption of Multiple Cellular Processes in HT-29 Epithelial Cells by Pseudomonas aeruginosa Exoenzyme S
- Creators
- Joan C Olson - ; and Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226Jennifer E Fraylick - ; and Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226Eileen M McGuffie - ; and Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226Katherine M Dolan - ; and Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226Timothy L Yahr - ; and Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226Dara W Frank - ; and Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226Timothy S Vincent - ; and Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226
- Resource Type
- Journal article
- Publication Details
- Infection and immunity, Vol.67(6), pp.2847-2854
- Publisher
- American Society for Microbiology
- DOI
- 10.1128/IAI.67.6.2847-2854.1999
- PMID
- 10338490
- PMCID
- PMC96591
- ISSN
- 0019-9567
- eISSN
- 1098-5522
- Language
- English
- Date published
- 06/1999
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984002375302771
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