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JAC Advance Access published online on March 8, 2006
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl056
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Received November 9, 2005
Revised February 7, 2006
Accepted February 10, 2006

Original article

Activity of novel non-amphipathic cationic antimicrobial peptides against Candida species

Lori L. Burrows 1 *, Margareta Stark 2, Celine Chan 2, Evgenia Glukhov 2, Selva Sinnadurai 3, and Charles M. Deber 4

1 Infection, Immunity, Injury and Repair, Hospital for Sick Children Research Institute, Toronto, ON, Canada; Department of Surgery, University of Toronto, Toronto, ON, Canada
2 Structural Biology and Biochemistry Programs, Hospital for Sick Children Research Institute, Toronto, ON, Canada
3 Infection, Immunity, Injury and Repair, Hospital for Sick Children Research Institute, Toronto, ON, Canada
4 Structural Biology and Biochemistry Programs, Hospital for Sick Children Research Institute, Toronto, ON, Canada; Department of Biochemistry, University of Toronto, Toronto, ON, Canada

* To whom correspondence should be addressed.
Lori L. Burrows, E-mail: burrowl{at}mcmaster.ca


  Abstract

Background and objectives: Candida species are problematic opportunistic pathogens in the hospital setting, where they are frequently associated with opportunistic infections of indwelling medical devices. There are only a few effective classes of antifungal agents currently available, and some species, such as Candida lusitaniae, Candida glabrata and Candida krusei, are intrinsically resistant to some of these drugs, further reducing existing therapeutic options. We have recently developed synthetic, non-amphipathic cationic antimicrobial peptides (CAPs) based on the structure of native hydrophobic membrane-spanning domains of integral membrane proteins. In this article, we report on the activity of these CAPs and new variants thereof against eight Candida species.

Methods and results: Using a combination of MIC, haemolysis, time-kill and biofilm killing assays, we demonstrate activity of CAPs in the micromolar range against eight Candida species, with little toxicity to mammalian cells. The synthetic peptides killed both the fluconazole-susceptible and fluconazole-resistant strains of Candida albicans, Candida tropicalis and C. glabrata by 4 logs or more within 3 h, and also killed pre-formed yeast biofilms on plastic surfaces.

Conclusions: These peptides show promise as a basis for development of novel, broad-spectrum antimicrobial agents.

Keywords: biofilms; fungi; CAPs; kaxins.
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