From the wealth of available data (see Additional Files 2, 3, 4, 5), we highlight in this report the most relevant conclusions. First, our study reinforces the idea that cell permeation is not the only mechanism required to fully describe the effect of, and response to, AMP in microorganisms [8–12]. We have also shown that PAF26 and melittin have common but also differential effects on yeast. Finally, a previously overlooked observation is that a significant part of the response relies on genes of unknown function, or with poorly informative GO terms associated to them. A remarkable example
of uncharacterized genes uncovered in our study is YLR162W, the only gene not related to ribosome biogenesis among the seven induced by melittin and repressed by PAF26 (Figure 2). It is a predicted gene this website of unknown function that codes for a small protein with potential transmembrane domains . An independent study has shown that over expression of YLR162W confers resistance to the plant antimicrobial peptide MiAMP1 in a susceptible yeast strain . Strikingly, our study indicates (in a different yeast genotype) that YLR162W reacts distinctly to different AMP, and thus highlights the
interest of studying its function since it might have an important and Ipatasertib nmr distinctive role in the response to AMP. BLAST searches do not show any homolog of this gene in known fungal sequences (data not shown). The role of the fungal cell wall in susceptibility to AMP The most obvious shared response is related to reinforcement of the cell wall. Among the 43 genes that were co-expressed in the peptide treatments (Figure 2), the only GO significant annotations were related to the fungal CW (Additional File 4.3). Additional studies found altered genes involved in CW maintenance in response to other antifungal agents or CW perturbants as well [38, 61, 62]. Among the previous genomic studies of the response to AMP in yeast, only the one that used the esculentin 1-21 peptide highlighted Tryptophan synthase CW responses at the transcriptomic level ,
while others did not [32, 33]. In addition, six genes (different from those found herein) were identified whose deletions confer increased sensitivity to Selleckchem GW786034 either dermaseptin S3 or magainin 2 . Our observations sustain that the improvement of CW integrity is a common response of S. cerevisiae to AMP. Further support arises from the data on BWG7a strain, which has a weakened CW phenotype related to a dysfunctional SSD1 allele  that compromises viability in the presence of AMP and at higher incubation temperatures (Additional File 1). Yeast cells are capable of reinforcing their CW when subjected to stress or damage conditions , and our study contributes to demonstrate that this is also the case after AMP treatment.