An integrated analysis of the effects of Esculentin 1–21 on Saccharomyces cerevisiae

Abstract

The antimicrobial peptide esculentin 1-21 (Esc 1-21) is a shorter synthetic version of the 46-residue peptide occurring in the Rana esculenta skin secretion. Here we propose an integrated proteomic and transcriptomic approach to interpret the biological effects of this peptide on Saccharomyces cerevisiae. We further investigated the response to this peptide by correlating the results of the transcriptome and proteome analysis with phenotypic effects. The results show that S. cerevisiae adapts to Esc 1-21 using the High Osmolarity Glycerol (HOG) pathway involved in osmotic tolerance and cell wall maintenance. Comparative proteomics reveals that Esc 1-21 causes downregulation of enzymes of the lower glycolytic pathway and in genes involved in spindle body formation and remodelling of cell-wall synthesis. Moreover the peptide induces downexpression of protein actin within 45 min and cells pre-treated with peptide show less sensitivity to osmotic stress and increased sensitivity to heat shock stress. The results obtained with the two different methodologies are in agreement at the cellular process levels. A combined approach may help elucidate the main aspects related to the effects of this peptide on the eukaryotic cell. The employment of different technologies may reveal the potential and limitations of each adapted approach in a prospective application for drug screening.

Esculentin‐1b(1–18) – a membrane‐active antimicrobial peptide that synergizes with antibiotics and modifies the expression level of a limited number of proteins in Escherichia coli

“…Note that only a few studies on the effect(s) of antimicrobial peptides on the proteomes of microorganisms have been performed to date. Interestingly, proteomic and transcriptomic analysis of the yeast Saccharomyces cerevisiae, following exposure to a similar antimicrobial peptide [esculentin-1a(1-21)], had shown downregulation of enzymes of the lower glycolytic pathway as well as a decrease in actin level, resulting in dramatic changes in cell physiology [57]. It is worthy of remark that both fragments of esculentin peptide were found to affect the integrity of the microbial plasma membrane and the synthesis of the microbial cell wall.…”

d-Amino acids incorporation in the frog skin-derived peptide esculentin-1a(1-21)NH2 is beneficial for its multiple functions

“…Recent studies demonstrated that esculentin-1a(1-21) NH 2 [Esc(1-21)] derived from the N-terminal region of the 46 residues frog skin AMP esculentin-1a (Gamberi et al 2007;Islas-Rodriguez et al 2009) is endowed with antimicrobial activity at high ionic concentrations, which is a crucial aspect due to the high-salt environment existing at the apical side of CF epithelial cells. In addition, in vivo experiments revealed that Esc(1-21) prolongs survival of murine models of P. aeruginosa-induced sepsis or lung infection, upon intravenous or intra-tracheal administration, respectively .…”

A genomic approach highlights common and diverse effects and determinants of susceptibility on the yeast Saccharomyces cerevisiae exposed to distinct antimicrobial peptides

“…Moreover, expression profiling is considered as a fingerprint to find common and distinct responses that could aid in the design of combined therapies of unrelated compounds, to which AMP might contribute. However, this type of studies are still scarce in the case of AMP, with only a few examples in bacteria [26-29] and fungi, mostly yeast [30-33]. Transcriptome profiling has been used to characterize the response of the model yeast Saccharomyces cerevisiae to distinct antifungals [34-39], including selected AMP [30,33].…”