This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kennedy, C. L. Articles by Rood, J. I. Search for Related Content PubMed PubMed Citation Articles by Kennedy, C. L. Articles by Rood, J. I.

 Previous Article  |  Next Article 

Infection and Immunity, March 2009, p. 943-951, Vol. 77, No. 3
0019-9567/09/$08.00+0     doi:10.1128/IAI.01267-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Pore-Forming Activity of Alpha-Toxin Is Essential for Clostridium septicum-Mediated Myonecrosis

Catherine L. Kennedy,^1, Dena Lyras,¹ Leanne M. Cordner,¹ Jody Melton-Witt,^2, John J. Emmins,³ Rodney K. Tweten,² and Julian I. Rood^1*

Australian Bacterial Pathogenesis Program, Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia,¹ Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190,² Department of Immunology, Monash University, Prahran, Victoria 3004, Australia³

Received 16 October 2008/ Returned for modification 26 November 2008/ Accepted 2 January 2009

Clostridium septicum alpha-toxin is a β-barrel pore-forming cytolysin that is functionally similar to aerolysin. Residues important in receptor binding, oligomerization, and pore formation have been identified; however, little is known about the activity of the toxin in an infection, although it is essential for disease. We have now shown that deletion of a small portion of the transmembrane domain, so that the toxin is no longer able to form pores, completely abrogates its ability to contribute to disease, as does replacement of the sole cysteine residue with leucine. However, although previous biochemical and cytotoxicity assays clearly indicated that mutations in residues important in oligomerization, binding, and prepore conversion greatly reduced activity or rendered the toxin inactive, once the mutated toxins were overexpressed by the natural host in the context of an infection it was found they were able to cause disease in a mouse model of myonecrosis. These results highlight the importance of testing the activity of virulence determinants in the normal host background and in an infectious disease context and provide unequivocal evidence that it is the ability of alpha-toxin to form a pore that confers its toxicity in vivo.

---

* Corresponding author. Mailing address: Australian Bacterial Pathogenesis Program, Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia. Phone: 61-399029157. Fax: 61-399029222. E-mail: julian.rood{at}med.monash.edu.au

Published ahead of print on 12 January 2009.

Editor: J. B. Bliska

Present address: Monash Institute for Medical Research, Monash University, Clayton 3800, Australia.

Present address: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720.

---

Infection and Immunity, March 2009, p. 943-951, Vol. 77, No. 3
0019-9567/09/$08.00+0     doi:10.1128/IAI.01267-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Uzal, F. A., Saputo, J., Sayeed, S., Vidal, J. E., Fisher, D. J., Poon, R., Adams, V., Fernandez-Miyakawa, M. E., Rood, J. I., McClane, B. A. (2009). Development and Application of New Mouse Models To Study the Pathogenesis of Clostridium perfringens Type C Enterotoxemias. Infect. Immun. 77: 5291-5299 [Abstract] [Full Text]  
• Odani, J. S., Blanchard, P. C., Adaska, J. M., Moeller, R. B., Uzal, F. A. (2009). Malignant edema in postpartum dairy cattle. jvdi 21: 920-924 [Abstract] [Full Text]