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Infect. Immun. doi:10.1128/IAI.00591-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Expression of Pseudomonas aeruginosa Toxin ExoS Effectively Induces Apoptosis in Host Cells

Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL 32610; Tianjin Key Laboratory of Food Nutrition and Safety, Tianjin University of Science and Technology, Tianjin, 300222, China

^* To whom correspondence should be addressed. Email: sjin{at}mgm.ufl.edu.

	Abstract

Pseudomonas aeruginosa is an opportunistic bacterial pathogen which primarily infects immunocompromised individuals and patients with cystic fibrosis. Invasive strains of P. aeruginosa is known to induce apoptosis at high frequency in HeLa and many other cell lines, a process that is dependent on the ADP-ribosylation (ADPRT) activity of a type III secreted protein ExoS. In our previous report, it was proposed that P. aeruginosa secreting ExoS, upon infection, shuts down host cell survival signal pathways by inhibiting ERK1/2 and p38 activation, and it activates pro-apoptotic pathways through activation of JNK1/2 leading ultimately to cytochrome c release and activation of caspases. In this study, we demonstrate that expression of ExoS in HeLa cells by eukaryotic expression vector effectively caused apoptosis in an ADPRT activity dependent manner, indicating that ExoS alone is sufficient to trigger apoptotic death of host cells independent of any other bacterial factors. By expressing an EGFP-ExoS fusion protein, we were able to directly correlate the death of HeLa cells with the presence of intracellular ExoS, and further proved the dependence of this process on both JNK activation and mitochondrial pro-apoptotic event. The cellular pathway responsible for the ExoS induced cytotoxicity appears to be well conserved, as expression of the ADPRT competent ExoS also induced rapid cell death in the Drosophila S2 cell lines. The presented study not only highlights the ability of ADPRT of ExoS to modulate host cell signaling, eventually leading to apoptosis, but also establishes ExoS as a valuable tool, in principle, for the elucidation of apoptosis mechanisms.

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