Novel Antifungal Peptaibols Emericellipsins A-E with Anticancer and Antibiofilm Potential from an alkalophilic fungus Emericellopsis alkalina

A novel complex of antimicrobial peptides with antifungal and cytotoxic activity was derived from the alkalophilic fungus Emericellopsis alkalina VKPM F-1428 isolated from soda soil. Novel peptides were assigned “Emericellipsins”, so-called because of their source fungus. The complete primary structure and detailed biological activity were determined for the five of them.

The dominant peptaibol - emericellipsin A (EmiA) showed strong antifungal, cytotoxic properties. The inhibitory activity of the major compound, EmiA against azole-resistant pathogenic Aspergillus spp., Candida spp. and Cryptococcus spp. was similar to amphotericin B. In addition, EmiA demonstrated low cytotoxic activity to the normal cell line (human postnatal fibroblasts, HPF) but possessed cancer selectivity to human myelogenous leukaemia (K-562) and human colon cancer (НСТ-116) cell lines. Emericellipsin A revealed negligible hemolytic activity at concentrations of 0–20 μM, making it a low-toxicity compound regarding normal human cells, but with a potentially high therapeutic index. The inhibited effect of EmiA on biofilm formation of clinical pathogens Staphylococcus aureus and Candida albicans was determined. The results obtained suggest EmiA as a natural compound with a prospect for using it to develop a promising antifungal agent for invasive mycoses therapy, especially for treatment multi-drug resistant aspergillosis and cryptococcosis