Antimicrobial Activity of Peptide-Mimetics Against Biofilm Cultures of Candida albicans

Objectives: Antimicrobial peptides (AMPs) such as magainins and defensins exhibit broad-spectrum antimicrobial activity against a wide range of pathogens including those leading to oral infections. However, as therapeutic agents they suffer from weaknesses, including difficulty in large-scale production, protease sensitivity, and immunomodulatory activities. To circumvent these issues, small-molecule mimetics have been designed to exhibit the amphipathic and cationic nature of AMPs without the protease sensitivity. We recently demonstrated the activity of one such mimetic against planktonic cultures of Streptococcus mutans with an MIC of less than 1μg/ml, that also exhibited dramatic synergy with chlorhexidine. This compound also killed biofilm cultures of S. mutans at concentrations below 50μg/ml. We were interested in examining other mimetic structures for their ability to kill cultures of Candida albicans and other Candida spp. in planktonic and biofilm forms. Methods: Standard MIC assays were performed to demonstrate the activity of the mimetic PMX30016 against planktonic cultures of C. albicans and a number of non-albicans Candida (NAC) species. Biofilms of C. albicans were developed on denture material, and fungicidal activity was measured using an XTT assay. Results: PMX30016 exhibited potent antifungal activity against azole-resistant and –sensitive strains of C. albicans, and against NAC, in the microgram/ml range. Furthermore, PMX30016 significantly reduced viable biofilm cultures of C. albicans at concentrations from 10-25μg/ml. Conclusions: Peptide-mimetics can form the basis for the development of novel therapies against Candidal infections. Supported by Polymedix, Inc., and NIH R01 DE14897.