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

 Previous Article  |  Next Article 

Infection and Immunity, August 2004, p. 4512-4520, Vol. 72, No. 8
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.8.4512-4520.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Cytotoxicity of Hydrogen Peroxide Produced by Enterococcus faecium

Terence I. Moy,1 Eleftherios Mylonakis,2 Stephen B. Calderwood,2,3 and Frederick M. Ausubel1*

Department of Genetics, Harvard Medical School, and Department of Molecular Biology, Massachusetts General Hospital,1 Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts 02114,2 Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 021153

Received 5 March 2004/ Returned for modification 29 April 2004/ Accepted 6 May 2004

Although the opportunistic bacterial pathogen Enterococcus faecium is a leading source of nosocomial infections, it appears to lack many of the overt virulence factors produced by other bacterial pathogens, and the underlying mechanism of pathogenesis is not clear. Using E. faecium-mediated killing of the nematode worm Caenorhabditis elegans as an indicator of toxicity, we determined that E. faecium produces hydrogen peroxide at levels that cause cellular damage. We identified E. faecium transposon insertion mutants with altered C. elegans killing activity, and these mutants were altered in hydrogen peroxide production. Mutation of an NADH oxidase-encoding gene eliminated nearly all NADH oxidase activity and reduced hydrogen peroxide production. Mutation of an NADH peroxidase-encoding gene resulted in the enhanced accumulation of hydrogen peroxide. E. faecium is able to produce hydrogen peroxide by using glycerol-3-phosphate oxidase, and addition of glycerol to the culture medium enhanced the killing of C. elegans. Conversely, addition of glucose, which leads to the down-regulation of glycerol metabolism, prevented both C. elegans killing and hydrogen peroxide production. Lastly, detoxification of hydrogen peroxide either by exogenously added catalase or by a C. elegans transgenic strain overproducing catalase prevented E. faecium-mediated killing. These results suggest that hydrogen peroxide produced by E. faecium has cytotoxic effects and highlight the utility of C. elegans pathogenicity models for identifying bacterial virulence factors.

* Corresponding author. Mailing address: Department of Molecular Biology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114. Phone: (617) 726-5950. Fax: (617) 726-5949. E-mail: ausubel{at}molbio.mgh.harvard.edu.

Editor: J. T. Barbieri

Infection and Immunity, August 2004, p. 4512-4520, Vol. 72, No. 8
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.8.4512-4520.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Jain, C., Yun, M., Politz, S. M., Rao, R. P. (2009). A Pathogenesis Assay Using Saccharomyces cerevisiae and Caenorhabditis elegans Reveals Novel Roles for Yeast AP-1, Yap1, and Host Dual Oxidase BLI-3 in Fungal Pathogenesis. Eukaryot Cell 8: 1218-1227 [Abstract] [Full Text]  
  • Chavez, V., Mohri-Shiomi, A., Maadani, A., Vega, L. A., Garsin, D. A. (2007). Oxidative Stress Enzymes Are Required for DAF-16-Mediated Immunity Due to Generation of Reactive Oxygen Species by Caenorhabditis elegans. Genetics 176: 1567-1577 [Abstract] [Full Text]  
  • Moy, T. I., Ball, A. R., Anklesaria, Z., Casadei, G., Lewis, K., Ausubel, F. M. (2006). From the Cover: Identification of novel antimicrobials using a live-animal infection model. Proc. Natl. Acad. Sci. USA 103: 10414-10419 [Abstract] [Full Text]  
  • van den Berg, M. C. W., Woerlee, J. Z., Ma, H., May, R. C. (2006). Sex-Dependent Resistance to the Pathogenic Fungus Cryptococcus neoformans. Genetics 173: 677-683 [Abstract] [Full Text]  
  • Tang, R. J., Breger, J., Idnurm, A., Gerik, K. J., Lodge, J. K., Heitman, J., Calderwood, S. B., Mylonakis, E. (2005). Cryptococcus neoformans Gene Involved in Mammalian Pathogenesis Identified by a Caenorhabditis elegans Progeny-Based Approach. Infect. Immun. 73: 8219-8225 [Abstract] [Full Text]  
  • Mylonakis, E., Aballay, A. (2005). Worms and Flies as Genetically Tractable Animal Models To Study Host-Pathogen Interactions. Infect. Immun. 73: 3833-3841 [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»