Antifungal Activity of 14-Helical β-Peptides against Planktonic Cells and Biofilms of Candida Species

Abstract

Candida albicans is the most prevalent cause of fungal infections and treatment is further complicated by the formation of drug resistant biofilms, often on the surfaces of implanted medical devices. In recent years, the incidence of fungal infections by other pathogenic Candida species such as C. glabrata, C. parapsilosis and C. tropicalis has increased. Amphiphilic, helical β-peptide structural mimetics of natural antimicrobial α-peptides have been shown to exhibit specific planktonic antifungal and anti-biofilm formation activity against C. albicans in vitro. Here, we demonstrate that β-peptides are also active against clinically isolated and drug resistant strains of C. albicans and against other opportunistic Candida spp. Different Candida species were susceptible to β-peptides to varying degrees, with C. tropicalis being the most and C. glabrata being the least susceptible. β-peptide hydrophobicity directly correlated with antifungal activity against all the Candida clinical strains and species tested. While β-peptides were largely ineffective at disrupting existing Candida biofilms, hydrophobic β-peptides were able to prevent the formation of C. albicans, C. glabrata, C. parapsilosis and C. tropicalis biofilms. The broad-spectrum antifungal activity of β-peptides against planktonic cells and in preventing biofilm formation suggests the promise of this class of molecules as therapeutics.

Antifungal Properties of Cationic Phenylene Ethynylenes and Their Impact on β-Glucan Exposure

“…and are thought to work by disrupting fungal plasma membrane integrity (53). C. glabrata is noted for its resistance to killing by cationic antimicrobial peptides in comparison to C. albicans and other pathogenic Candida species (54)(55)(56). Furthermore, the decreased ability of EO-OPE-DABCO to kill C. glabrata resembles the results of a previous study, in which a 10-g/ml concentration of the compound failed to kill 99% of S. cerevisiae yeast cells, even after an hour in the light (23).…”

Eradication Effect of Javanese Turmeric (Curcuma Xanthorrhiza. Roxb.) Extract on the Early Phase of Candida Albicans Biofilm

“…In the intermediate phase, the yeast cells undergo a morphological change from yeast cells to filamentous cells, which indicate the changes from a commensal microorganism to a pathogen. As filamentous cells, C. albicans might penetrate the epithelial tissue and increase its resistance to the function of the host immune system [7,8]. The last phase of biofilm formation is maturation, which occurs by extracellular matrix accumulation and increased resistance to antifungal agents [7].…”

“…As filamentous cells, C. albicans might penetrate the epithelial tissue and increase its resistance to the function of the host immune system [7,8]. The last phase of biofilm formation is maturation, which occurs by extracellular matrix accumulation and increased resistance to antifungal agents [7]. Compared to its planctonic form, the biofilm form of the microorganism has increased stability and resistance to threatening environments, such as the limited availability of nutrition and the presence of antimicroorganism agents [9].…”

“…The adhesion of yeast cells on the surface of host tissues, which is the first stage of biofilm formation, occurs in 1-2 h. At 3 h, the yeast starts to proliferate and form colonies. At 6-11 h, C. albicans develops a complex structure with hyphal formation [7]. The common clinical procedure in the treatment of oral candidiasis is to apply a topical antifungal agent such as nystatin.…”

Incorporation of β-Amino Acids Enhances the Antifungal Activity and Selectivity of the Helical Antimicrobial Peptide Aurein 1.2

“…7 However, these peptidomimetic AMPs exhibit structural folding patterns that are distinct from those of natural AMPs, preventing conservation of side-chain presentation and often adversely influencing AMP interactions with target cell membranes. In prior work, we generated antifungal β-peptides that were structurally inspired by cationic, amphiphilic AMPs 9, 10 . While these β-peptides exhibit the global amphiphilicity of AMPs, the side chain organization around the 14-helix periphery differs from that of native antimicrobial α-peptides.…”