ABSTRACT
Aim: An IsCT analogue peptide (PepM3) was designed based on structural studies of wasp mastoparans and tested against Candida albicans. Its effects on fungal cell membranes and toxicity were evaluated. Materials & methods: Antifungal activity was analyzed using a microdilution susceptibility test. Toxicity was assessed using human skin keratinocytes (HaCaT) and zebrafish embryos. Results: PepM3 demonstrated activity against C. albicans and a synergistic effect with amphotericin B. The peptide presented fungicidal action with damage to the fungal cell membrane, low toxicity in HaCat cells and was nonteratogenic in zebrafish embryos. Conclusion: Evaluating structural modifications is essential for the development of new agents with potential activity against fungal pathogens and for the reduction of toxic and teratogenic effects.
Subject(s)
Candida albicans , Zebrafish , Animals , Humans , Antifungal Agents/toxicity , Antifungal Agents/chemistry , Amphotericin B/pharmacology , Peptides/toxicity , Microbial Sensitivity TestsABSTRACT
Aim: In this work, mastoparan analog peptides from wasp venom were tested against Candida albicans and safety assays were performed using cell culture and model zebrafish. Materials & methods: Minimal inhibitory concentration was determined and toxicity was performed using human skin keratinocyte and embryo zebrafish. Also, permeation of peptides through embryo chorion was performed. Results: The peptides demonstrated anti-C. albicans activity, with low cytotoxicity and nonteratogenicity in Danio rerio. The compounds had different permeation through chorion, suggesting that this occurs due to modifications in their amino acid sequence. Conclusion: The results showed that the studied peptides can be used as structural study models for novel potential antifungal agents.
Subject(s)
Antifungal Agents/pharmacology , Candida albicans/drug effects , Intercellular Signaling Peptides and Proteins/pharmacology , Peptides/pharmacology , Wasp Venoms/pharmacology , Animals , Antifungal Agents/administration & dosage , Antifungal Agents/adverse effects , Antifungal Agents/toxicity , Cell Survival/drug effects , Cells, Cultured , Drug-Related Side Effects and Adverse Reactions/pathology , Humans , Intercellular Signaling Peptides and Proteins/administration & dosage , Intercellular Signaling Peptides and Proteins/adverse effects , Intercellular Signaling Peptides and Proteins/toxicity , Keratinocytes/drug effects , Microbial Sensitivity Tests , Peptides/administration & dosage , Peptides/adverse effects , Peptides/toxicity , Wasp Venoms/administration & dosage , Wasp Venoms/adverse effects , Wasp Venoms/toxicity , ZebrafishABSTRACT
Biofilm formation is an important virulence factor for pathogenic fungi. Both yeasts and filamentous fungi can adhere to biotic and abiotic surfaces, developing into highly organized communities that are resistant to antimicrobials and environmental conditions. In recent years, new genera of fungi have been correlated with biofilm formation. However, Candida biofilms remain the most widely studied from the morphological and molecular perspectives. Biofilms formed by yeast and filamentous fungi present differences, and studies of polymicrobial communities have become increasingly important. A key feature of resistance is the extracellular matrix, which covers and protects biofilm cells from the surrounding environment. Furthermore, to achieve cell-cell communication, microorganisms secrete quorum-sensing molecules that control their biological activities and behaviors and play a role in fungal resistance and pathogenicity. Several in vitro techniques have been developed to study fungal biofilms, from colorimetric methods to omics approaches that aim to identify new therapeutic strategies by developing new compounds to combat these microbial communities as well as new diagnostic tools to identify these complex formations in vivo. In this review, recent advances related to pathogenic fungal biofilms are addressed.