albicans biofilms. Once it reaches
the cell, KSL-W can potentially act on the cytoplasmic membrane as well as on intracellular targets [49–51]. The action INK1197 price of KSL-W against C. albicans may operate through the modulated expression of certain C. albicans genes that control growth , transition , and biofilm formation . We selleckchem therefore examined the effect of KSL-W on a number of genes either directly or indirectly involved in phase transition and biofilm formation. EFG1 and NRG1 expression was assessed under hyphae/non-hyphae-inducing conditions. Our results show that KSL-W increased NRG1 mRNA expression twofold under non-hyphae-inducing conditions; however, under hyphae-inducing conditions, KSL-W significantly reduced NRG1 gene expression. These findings contrast with other reports that an increased NRG1 Sepantronium expression contributes to repressing various hypha-specific
genes [55, 56]. This confirms that the effect of KSL-W in controlling C. albicans virulence does not take place through NRG1. KSL-W was also able to decrease EFG1 mRNA expression, when C. albicans was maintained under hyphae-inducing conditions. EFG1p has been found to be a central regulator of C. albicans, as it is required for the development of a true hyphal growth form, and EFG1 is considered to be essential in the interactions between C. albicans and human host cells [7, 8]. The downregulation of this gene by KSL-W points to the singular role of this
antifungal peptide. Thus the effect of KSL-W on C. albicans transition can be manifested through a repression of certain genes, such as EFG1 and NRG1. KSL-W has a significant inhibitory effect on EAP1 mRNA expression. As a member of the Farnesyltransferase GPI-CWP family [5, 57], deleting EAP1 can reduce the adhesion of C. albicans to different surfaces. This suggests that treatment with KSL-W may reduce EAP1 expression, which in turn may contribute to reducing C. albicans adhesion and ultimately, biofilm formation and pathogenesis. KSL-W was also shown to reduce HWP1 mRNA expression, particularly when C. albicans was cultured under hyphae-inducing conditions. HWP1 is a downstream component of the cAMP-dependent PKA pathway and is positively regulated by EFG1 . The transcript level of HWP1 decreased with the KSL-W treatment at low and high concentrations. These data suggest that KSL-W indeed impacts the activity of the cAMP–EFG1 pathway and leads to an alteration of C. albicans growth and morphogenesis. Further studies are therefore required to investigate the invasion/virulence of KSL-W-treated C. albicans. It is well known that Candida pathogenesis can be established by virtue of Candida growth and yeast-to-hyphae morphogenesis. Specific SAP genes were found to be preferentially expressed by Candida hyphal forms [10, 15, 59]. Because KSL-W downregulated C. albicans growth and transition, this may have occurred through a modulation of the SAP genes.