Genetic Screening of a Saccharomyces Cerevisiae Strain Provides Insight Into the Cellular Molecular Response Towards Artificial Synthetic Peptides

The development of new drugs to treat fungal infections has become an urgent necessity due to the increasing resistant strains of fungi and bacteria, the currently limited selection of treatment and its adverse side effects along with the increasing numbers of immunocompromised patients. A possible solution to this problem is the development of β-peptides. These foldamers, are short nanorods made from artificial amino acids, that have been designed to mimic natural antimicrobial peptides known as host-defense peptides (HDPs). HDPs are made by most living organisms as a way to counteract a broad spectrum of microbial attacks, which include bacteria and fungi. Some advantages of using β-peptides compared to natural HDPs are: their conformational stability, predictable folding behavior, resistance to proteases and activity at physiological salt concentrations. From previous studies, the selected β-peptide sequence, (ACHC-β³V-β³K)₃ nicknamed as (ACHC-V-K)₃, because of its decent antifungal potency compared to amphotericin B properties and its low toxicity against erythrocytes. The mechanism of action of β-peptides still remains unknown and in order to find possible routes of action we hypothesized that, using a genetic molecular approach, we can identify genes that are actively involved in the phenotypic response the genetic model S. cerevisiae. Using this approach, 15 genes have been identified, three of which are being discussed in this work (HSP33, FEN2, SRN2).