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Journal of Bacteriology, April 2008, p. 2814-2821, Vol. 190, No. 8
0021-9193/08/$08.00+0     doi:10.1128/JB.01567-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The Type III Toxins of Pseudomonas aeruginosa Disrupt Epithelial Barrier Function{triangledown}

Grace Soong, Dane Parker, Mariah Magargee, and Alice S. Prince*

Department of Pediatrics and Pharmacology, College of Physicians & Surgeons, Columbia University, New York, New York 10032

Received 28 September 2007/ Accepted 20 December 2007

The type III secreted toxins of Pseudomonas aeruginosa are important virulence factors associated with clinically important infection. However, their effects on bacterial invasion across mucosal surfaces have not been well characterized. One of the most commonly expressed toxins, ExoS, has two domains that are predicted to affect cytoskeletal integrity, including a GTPase-activating protein (GAP) domain, which targets Rho, a major regulator of actin polymerization; and an ADP-ribosylating domain that affects the ERM proteins, which link the plasma membrane to the actin cytoskeleton. The activities of these toxins, and ExoS specifically, on the permeability properties of polarized airway epithelial cells with intact tight junctions were examined. Strains expressing type III toxins altered the distribution of the tight junction proteins ZO-1 and occludin and were able to transmigrate across polarized airway epithelial monolayers, in contrast to {Delta}STY mutants. These effects on epithelial permeability were associated with the ADP-ribosylating domain of ExoS, as bacteria expressing plasmids lacking expression of the ExoS GAP activity nonetheless increased the permeation of fluorescent dextrans, as well as bacteria, across polarized airway epithelial cells. Treatment of epithelial cells with cytochalasin D depolymerized actin filaments and increased permeation across the monolayers but did not eliminate the differential effects of wild-type and toxin-negative mutants on the epithelial cells, suggesting that additional epithelial targets are involved. Confocal imaging studies demonstrated that ZO-1, occludin, and ezrin undergo substantial redistribution in human airway cells intoxicated by ExoS, -T, and -Y. These studies support the hypothesis that type III toxins enhance P. aeruginosa's invasive capabilities by interacting with multiple eukaryotic cytoskeletal components.

* Corresponding author. Mailing address: Columbia University, 650 West 168th Street, BB4-416, New York, NY 10032. Phone: (212) 305-4193. Fax: (212) 342-5728. E-mail: asp7{at}columbia.edu

{triangledown} Published ahead of print on 28 December 2007.

Journal of Bacteriology, April 2008, p. 2814-2821, Vol. 190, No. 8
0021-9193/08/$08.00+0     doi:10.1128/JB.01567-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Goldberg, J. B., Hancock, R. E. W., Parales, R. E., Loper, J., Cornelis, P. (2008). Pseudomonas 2007. J. Bacteriol. 190: 2649-2662 [Full Text]  


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