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


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.
Burrows
Lori L
LL
Infection, Immunity, Injury and Repair, Hospital for Sick Children Research Institute, Toronto, ON, Canada. burrowl@mcmaster.ca
Stark
Margareta
M
Chan
Celine
C
Glukhov
Evgenia
E
Sinnadurai
Selva
S
Deber
Charles M
CM
D000935:Antifungal Agents / Q000009:adverse effects / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000009:adverse effects / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002175:Candida / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D004912:Erythrocytes / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D013045:Species Specificity; D013997:Time Factors
D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides