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Infection and Immunity, March 2009, p. 977-983, Vol. 77, No. 3
0019-9567/09/$08.00+0     doi:10.1128/IAI.00920-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The H35A Mutated Alpha-Toxin Interferes with Cytotoxicity of Staphylococcal Alpha-Toxin{triangledown}

Xudong Liang, Meiying Yan, and Yinduo Ji*

Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota 55108

Received 24 July 2008/ Returned for modification 21 October 2008/ Accepted 16 December 2008

Staphylococcal alpha-toxin is an important virulence factor for Staphylococcus aureus to cause severe infections. In this study, we explored whether the toxoid of alpha-toxin may be utilized to block the toxicity of wild-type alpha-toxin. We created a series of H35A mutated alpha-toxin expression strains and revealed that the H35A mutation eliminates the activity of alpha-toxin using a human lung epithelial cell line (A549). More importantly, we found that either the pretreatment or simultaneous treatment of the epithelial cells with alpha-toxin-H35A completely disrupted the cytotoxicity of alpha-toxin. Specifically, we demonstrated that alpha-toxin-H35A can effectively interfere with the pore formation and the internalization of alpha-toxin using cytotoxicity and immunofluorescence assays. In addition, we found that the removal of either the 30-amino-acid (aa) or 99-aa C-terminal region of alpha-toxin-H35A reactivated its cytotoxicity, indicating that interactions between the alanine residue at position 35 and these C-terminal regions may be associated with interrupting the toxic activity of alpha-toxin-H35A. Taken together, these results suggest that the alpha-toxin-H35A protein may be developed as a potential alternative therapeutic agent for treating early stages of S. aureus infections.

* Corresponding author. Mailing address: Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, 1971 Commonwealth Ave., St. Paul, MN 55108. Phone: (612) 624-2757. Fax: (612) 625-5203. E-mail: jixxx002{at}umn.edu

{triangledown} Published ahead of print on 22 December 2008.

Editor: V. J. DiRita

Infection and Immunity, March 2009, p. 977-983, Vol. 77, No. 3
0019-9567/09/$08.00+0     doi:10.1128/IAI.00920-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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