On the other hand, deletion of specific CW proteins sensitize yeast to the antibacterial lantibiotic nisin [66]. Further, PAF26 induced severe mycelial growth and cell-shape defects to the fungus P. digitatum [46], changes that are typical for compounds affecting the cell wall. Our assays showed only a limited number of gene deletions related to CW that have an effect on sensitivity to PAF26 or melittin. Even in these examples, the magnitude of the phenotype of the mutants (i.e., changes in sensitivity)

is modest compared to that of mutants related to ribosome biogenesis, arginine metabolism, sphingolipid or HSP related genes (compare Figures 4 and 5). This LY3023414 mouse holds even for genes such as the above mentioned SSD1, which mediates deposition of other CW proteins in S. cerevisiae [56]. The corresponding deletion strain has a damaged CW as confirmed by hyper-sensitivity to SDS

or CFW, but comparatively only a minor increase in susceptibility to AMP as demonstrated in two genetic backgrounds C646 price (BY4741 and RAY3A, see also Additional File 6). A similar phenotype was observed in other strains such as Δecm33. Microscopy and flow cytometry studies in Δssd1 or Δecm33 showed a correlation between a higher sensitivity and an increase of PAF26 uptake of cells (Figure 7), demonstrating that CW components modulate the interaction with peptides. Function redundancy might explain the lack of a dramatic change in the susceptibility in mutants related to CW. Therefore multiple deletions

would be expected to have a higher impact and are being studied in our laboratory. However, our current data do not support this view either, as illustrated with the triple deletion of PIR genes in the RAY3A background (Additional File 6). Even in the case of gene deletions from MAPK Thiazovivin cost signalling cascades involved in CW construction and response to stress [51], we did not find major differences in sensitivity Adenosine triphosphate to peptides under our assay conditions (Additional File 7). Representative examples are STE2 that was highly repressed by both peptides, or SLT2, PBS2 and HOG1, whose deletants are hypersensitive to CW interfering compounds. This result contrasts with previous data in which mutations in the HOG osmoregulatory pathway in the case of the peptide histatin [31] or the RHO1-SLT2 CW growth pathway in a plant defensin Pn-AMP1 [67] result in hypersensitivity. Other CW-related gene deletions did not show significant differences in susceptibility to peptides and even in a limited number of examples (as Δsed1) a slight higher resistance was observed. It has been described that specific gene deletions result in counteracting mechanisms to reinforce CW by enhancing levels of specific CW constituents [64].