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Science 3 March 2000:
Vol. 287. no. 5458, pp. 1655 - 1658
DOI: 10.1126/science.287.5458.1655
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Reports

Salmonella Pathogenicity Island 2-Dependent Evasion of the Phagocyte NADPH Oxidase

Andrés Vazquez-Torres, 1 Yisheng Xu, 1 Jessica Jones-Carson, 1 David W. Holden, 2 Scott M. Lucia, 1 Mary C. Dinauer, 3 Pietro Mastroeni, 4* Ferric C. Fang 1dagger

A type III protein secretion system encoded by Salmonella pathogenicity island 2 (SPI2) has been found to be required for virulence and survival within macrophages. Here, SPI2 was shown to allow Salmonella typhimurium to avoid NADPH oxidase-dependent killing by macrophages. The ability of SPI2-mutant bacteria to survive in macrophages and to cause lethal infection in mice was restored by abrogation of the NADPH oxidase-dependent respiratory burst. Ultrastructural and immunofluorescence microscopy demonstrated efficient localization of the NADPH oxidase in the proximity of vacuoles containing SPI2-mutant but not wild-type bacteria, suggesting that SPI2 interferes with trafficking of oxidase-containing vesicles to the phagosome.

1 Departments of Medicine, Pathology, and Microbiology, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
2 Department of Infectious Diseases, Imperial College School of Medicine, London W12 ONN, UK.
3 Indiana University School of Medicine, Indianapolis, IN 46202, USA.
4 Department of Biochemistry, Imperial College of Medicine and Technology, London SW7 2BZ, UK.
*   Present address: Centre for Veterinary Science, University of Cambridge, Cambridge CB3 0ES, UK.

dagger    To whom correspondence should be addressed. E-mail: ferric.fang{at}uchsc.edu

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M. Lu, X. Tang, and J.-M. Zhou (2001)
PLANT CELL 13, 437-447
   Abstract »    Full Text »
Salmonella Pathogenicity Island 2 Influences Both Systemic Salmonellosis and Salmonella-Induced Enteritis in Calves.
J. Bispham, B. N. Tripathi, P. R. Watson, and T. S. Wallis (2001)
Infect. Immun. 69, 367-377
   Abstract »    Full Text »    PDF »
Human Granulocytic Ehrlichiosis Agent Inhibits Superoxide Anion Generation by Human Neutrophils.
J. Mott and Y. Rikihisa (2000)
Infect. Immun. 68, 6697-6703
   Abstract »    Full Text »    PDF »
Characterization of Escherichia coli DNA Lesions Generated within J774 Macrophages.
E. Schlosser-Silverman, M. Elgrably-Weiss, I. Rosenshine, R. Kohen, and S. Altuvia (2000)
J. Bacteriol. 182, 5225-5230
   Abstract »    Full Text »
Inherited Neutrophil Disorders: Molecular Basis and New Therapies.
M. C. Dinauer, J. A. Lekstrom-Himes, and D. C. Dale (2000)
Hematology 2000, 303-318
   Abstract »    Full Text »    PDF »
Defective localization of the NADPH phagocyte oxidase to Salmonella-containing phagosomes in tumor necrosis factor p55 receptor-deficient macrophages.
A. Vazquez-Torres, G. Fantuzzi, C. K. Edwards III, C. A. Dinarello, and F. C. Fang (2001)
PNAS 98, 2561-2565
   Abstract »    Full Text »    PDF »
Salmonella Pathogenicity Island 2 Mediates Protection of Intracellular Salmonella from Reactive Nitrogen Intermediates.
D. Chakravortty, I. Hansen-Wester, and M. Hensel (2002)
J. Exp. Med. 195, 1155-1166
   Abstract »    Full Text »    PDF »


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