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

Lori L Burrows1, Margareta Stark, Celine Chan

  • 1Infection, Immunity, Injury and Repair, Hospital for Sick Children Research Institute, Toronto, ON, Canada. burrowl@mcmaster.ca

Abstract

Insights

New synthetic cationic antimicrobial peptides (CAPs) show broad-spectrum activity against eight Candida species, including drug-resistant strains. These CAPs effectively kill yeast and biofilms with minimal toxicity to human cells, offering potential for novel antifungal therapies.

Area of Science:

  • Antimicrobial peptide research
  • Medical mycology
  • Drug discovery

Background:

  • Candida species are opportunistic pathogens causing hospital-acquired infections, often linked to medical devices.
  • Limited antifungal drug options exist, compounded by intrinsic resistance in species like Candida lusitaniae, Candida glabrata, and Candida krusei.
  • Synthetic, non-amphipathic cationic antimicrobial peptides (CAPs) were developed based on integral membrane protein domains.

Purpose of the Study:

  • To evaluate the antifungal activity of novel synthetic CAPs and their variants against eight Candida species.
  • To assess the efficacy of CAPs against both susceptible and resistant Candida strains.
  • To determine the safety profile of CAPs concerning mammalian cell toxicity.

Main Methods:

  • Minimum Inhibitory Concentration (MIC) assays
  • Haemolysis assays
  • Time-kill assays
  • Biofilm killing assays

Main Results:

  • CAPs demonstrated potent activity in the micromolar range against eight Candida species.
  • Synthetic peptides effectively killed fluconazole-susceptible and fluconazole-resistant strains of Candida albicans, Candida tropicalis, and Candida glabrata within 3 hours (≥4 log reduction).
  • CAPs exhibited low toxicity to mammalian cells and eradicated pre-formed yeast biofilms on plastic surfaces.

Conclusions:

  • The synthetic CAPs show significant promise as a foundation for developing new broad-spectrum antimicrobial agents.
  • These findings suggest a potential new therapeutic avenue for combating challenging Candida infections.

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