Such analyses might also highlight novel targets for antimicrobials. 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 AZD9291 mouse profiling has been used to characterize the response of the model yeast Saccharomyces cerevisiae to distinct antifungals [34–39], including selected AMP [30, 33]. In this study we aim to compare at a genomic scale the effects onto S. cerevisiae of two AMP with distinctive properties. Melittin is an α-helical membrane active peptide identified from honeybee venom that is recognized as a model pore-forming peptide for the study of peptide interaction with lipid bilayers and cell permeating properties [40]. On the other hand, PAF26 is a short de novo-designed hexapeptide [41], which shares sequence similarity with other AMP from natural [42] or synthetic origin

[43, 44]. It has activity against plant pathogenic fungi as well as several microorganisms of clinical relevance, including the yeast Candida and several dermatophytic fungi [45]. PAF26 at low micromolar (sub-inhibitory) concentrations has been recently shown to have cell penetrating properties in MLN2238 in vitro the mycelium and conidia of the filamentous plant pathogen Penicillium digitatum [46] and the model fungus Neurospora crassa (A. Muñoz and N. Read, unpublished observations). Contrary to melittin, PAF26 is less active against

bacteria and is not haemolytic under assay conditions in which other peptides including melittin are [45]. We combined global analyses of transcriptomic changes upon exposure of S. cerevisiae to sub-lethal concentrations of either PAF26 or melittin with sensitivity PLEK2 tests of strains lacking genes identified by the transcriptomic data. Our results both reinforce and extend similar studies undertaken previously with two unrelated α-helical AMP [33], and reveal that PAF26 and melittin have common but also distinctive effects on yeast. Results Antimicrobial activity of peptides PAF26 and melittin against S. cerevisiae PAF26 and the pore-forming peptide melittin inhibited yeast growth [41], as was confirmed herein with strain FY1679 (Figure 1A and Additional File 1) in experiments that show a slight 2-fold higher potency of melittin. Dose-response experiments with additional strains of yeast with distinct genetic backgrounds and at two temperatures of incubation confirmed the activity of both peptides and also indicated a differential sensitivity of strains (Additional File 1).