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 Vallon-Eberhard, A.
Right arrow Articles by Shai, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vallon-Eberhard, A.
Right arrow Articles by Shai, Y.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, September 2008, p. 3118-3126, Vol. 52, No. 9
0066-4804/08/$08.00+0     doi:10.1128/AAC.00526-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Efficient Clearance of Aspergillus fumigatus in Murine Lungs by an Ultrashort Antimicrobial Lipopeptide, Palmitoyl-Lys-Ala-DAla-Lys {triangledown}

Alexandra Vallon-Eberhard,1,{dagger} Arik Makovitzki,2,{dagger} Anne Beauvais,3 Jean-Paul Latgé,3 Steffen Jung,1 and Yechiel Shai2*

Department of Immunology,1 Department of Biological Chemistry, Weizmann Institute of Science, 76100 Rehovot, Israel,2 Unité des Aspergillus, Institut Pasteur, Paris, France3

Received 23 April 2008/ Returned for modification 28 May 2008/ Accepted 29 June 2008

Aspergillus fumigatus is an opportunistic fungal pathogen responsible for invasive aspergillosis in immunocompromised individuals. The inefficiency of antifungal agents and high mortality rate resulting from invasive aspergillosis remain major clinical concerns. Recently, we reported on a new family of ultrashort cationic lipopeptides active in vitro against fungi. Mode of action studies supported a membranolytic or a detergent-like effect. Here, we screened several lipopeptides in vitro for their anti-A. fumigatus activity. To investigate the therapeutic properties of the selected peptides in vivo, we challenged immunosuppressed C57BL/6 wild-type mice intranasally with DsRed-labeled A. fumigatus conidia and subsequently treated the animals locally with the lipopeptides. Confocal microscopic analysis revealed the degradation of DsRed-labeled hyphal forms and residual conidia in the lungs of the mice. The most efficient peptide was tested further using a survival assay and was found to significantly prolong the life of the treated animals, whereas no mice survived with the current standard antifungal treatment with amphotericin B. Moreover, as opposed to the drug-treated lungs, the peptide-treated lungs did not display any toxicity of the peptide. Our results highlight the potential of this family of lipopeptides for the treatment of pulmonary invasive aspergillosis.

* Corresponding author. Mailing address: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel. Phone: 972-8-9342711. Fax: 972-8-9344112. E-mail: Yechiel.Shai{at}weizmann.ac.il

{triangledown} Published ahead of print on 7 July 2008.

{dagger} These authors contributed equally to the study.

Antimicrobial Agents and Chemotherapy, September 2008, p. 3118-3126, Vol. 52, No. 9
0066-4804/08/$08.00+0     doi:10.1128/AAC.00526-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Choi, S., Isaacs, A., Clements, D., Liu, D., Kim, H., Scott, R. W., Winkler, J. D., DeGrado, W. F. (2009). De novo design and in vivo activity of conformationally restrained antimicrobial arylamide foldamers. Proc. Natl. Acad. Sci. USA 106: 6968-6973 [Abstract] [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»