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Infection and Immunity, October 2003, p. 6035-6044, Vol. 71, No. 10
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.10.6035-6044.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Effector ExoU from the Type III Secretion System Is an Important Modulator of Gene Expression in Lung Epithelial Cells in Response to Pseudomonas aeruginosa Infection

Institute for Molecular Bioscience,¹ Cooperative Research Centre for Inflammatory Diseases, University of Queensland, Brisbane, St. Lucia 4072, Queensland 4072, Australia,² Departments of Medicine, Microbiology, and Immunology and the Cardiovascular Research Institute, University of California at San Francisco, San Francisco, California 94143³

Received 27 November 2002/ Returned for modification 10 March 2003/ Accepted 30 May 2003

Pseudomonas aeruginosa is an important pathogen in immunocompromised patients and secretes a diverse set of virulence factors that aid colonization and influence host cell defenses. An important early step in the establishment of infection is the production of type III-secreted effectors translocated into host cells by the bacteria. We used cDNA microarrays to compare the transcriptomic response of lung epithelial cells to P. aeruginosa mutants defective in type IV pili, the type III secretion apparatus, or in the production of specific type III-secreted effectors. Of the 18,000 cDNA clones analyzed, 55 were induced or repressed after 4 h of infection and could be classified into four different expression patterns. These include (i) host genes that are induced or repressed in a type III secretion-independent manner (32 clones), (ii) host genes induced specifically by ExoU (20 clones), and (iii) host genes induced in an ExoU-independent but type III secretion dependent manner (3 clones). In particular, ExoU was essential for the expression of immediate-early response genes, including the transcription factor c-Fos. ExoU-dependent gene expression was mediated in part by early and transient activation of the AP1 transcription factor complex. In conclusion, the present study provides a detailed insight into the response of epithelial cells to infection and indicates the significant role played by the type III virulence mechanism in the initial host response.

Editor: V. J. DiRita

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