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Infection and Immunity, December 2002, p. 7054-7062, Vol. 70, No. 12
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.12.7054-7062.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The Bacterial Redox Protein Azurin Induces Apoptosis in J774 Macrophages through Complex Formation and Stabilization of the Tumor Suppressor Protein p53

Tohru Yamada,1 Masatoshi Goto,1 Vasu Punj,1 Olga Zaborina,1,{dagger} Kazuhide Kimbara,1,{ddagger} T. K. Das Gupta,2 and A. M. Chakrabarty1*

Department of Microbiology & Immunology,1 Department of Surgical Oncology, University of Illinois College of Medicine, Chicago, Illinois 606122

Received 23 May 2002/ Returned for modification 29 August 2002/ Accepted 6 September 2002

Two redox proteins, azurin and cytochrome c551 elaborated by Pseudomonas aeruginosa, demonstrate significant cytotoxic activity towards macrophages. Azurin can enter macrophages, localize in the cytosol and nuclear fractions, and induce apoptosis. Two redox-negative mutants of azurin have less cytotoxicity than does wild-type (wt) azurin. Azurin has been shown to form a complex with the tumor suppressor protein p53, a known inducer of apoptosis, thereby stabilizing it and enhancing its intracellular level. A higher level of reactive oxygen species (ROS), generated during treatment of macrophages with wt azurin, correlates with its cytotoxicity. Treatment with some ROS-removing antioxidants greatly reduces azurin-mediated cytotoxicity, thus demonstrating a novel virulence property of this bacterial redox protein.

* Corresponding author. Mailing address: Department of Microbiology & Immunology, University of Illinois College of Medicine, 835 S. Wolcott Ave., Chicago, IL 60612. Phone: (312) 996-4586. Fax: (312) 996-6415. E-mail: pseudomo{at}uic.edu.

Editor: J. T. Barbieri

{dagger} Present address: Department of Surgery, University of Chicago, Chicago, Ill.

{ddagger} Present address: Environmental Biotechnology Laboratory, Railway Technical Research Institute, Tokyo 185-8540, Japan.

Infection and Immunity, December 2002, p. 7054-7062, Vol. 70, No. 12
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.12.7054-7062.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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