JAC Advance Access originally published online on March 8, 2006
Journal of Antimicrobial Chemotherapy 2006 57(5):899-907; doi:10.1093/jac/dkl056
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Activity of novel non-amphipathic cationic antimicrobial peptides against Candida species
1 Infection, Immunity, Injury and Repair, Hospital for Sick Children Research Institute, Toronto, ON, Canada; 2 Department of Surgery, University of Toronto, Toronto, ON, Canada; 3 Structural Biology and Biochemistry Programs, Hospital for Sick Children Research Institute, Toronto, ON, Canada; 4 Department of Biochemistry, University of Toronto, Toronto, ON, Canada
Received 9 November 2005; returned 2 December 2005; revised 7 February 2006; accepted 10 February 2006
* Correspondence address. Department of Biochemistry, Room 4H18, Health Sciences Centre, McMaster University, 1200 Main Street West Hamilton, ON L8S 4L8, Canada. Tel: +1-905-525-9140 ext. 22029; Fax: +1-905-522-9033; E-mail: burrowl{at}mcmaster.ca
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