albicans. The importance of Xog1 for structural integrity is underlined by the fact that a mutation in XOG1 affects cell selleck products wall integrity (Gonzalez et al., 1997), suggesting it might also possess transglucosylase activity. Similarly involved in cell wall
integrity is the transglucosylase Bgl2 as the knockout mutant displays a wall defect and forms cell aggregates in stationary-phase cultures (Hartland et al., 1991; Sarthy et al., 1997). Bgl2 was only found in the medium at low levels at 42 °C and during fluconazole exposure. In S. cerevisiae, ScBgl2 is strongly associated with β-1,3-glucan and is robust enough to stay functionally active after SDS boiling (Klebl & Tanner, 1989). Intriguingly, free Bgl2 in the medium was able to bind β-1,3-glucan as well as chitin. Both Bgl2 and Xog1, together with the GPI-anchored transglycosylase Phr1, have been recently suggested to function in a β-glucan delivery system to the extracellular matrix, contributing to biofilm formation and drug resistance (Taff et al., 2012). Individual knockout mutants
formed less persistent biofilms that sequestered less fluconazole than the reference strain. Intriguingly, this phenotype did not affect the overall composition of β-glucan in the wall itself. As PHR1 and PHR2 serve the same function but are expressed at a different pH, Phr2 might contribute to biofilm formation as well. Taken together, this suggests that extracellular matrix formation is a key function of the secretome, leading to increased resistance to different stresses (e.g. antifungals). buy FDA approved Drug Library Secretory proteins in the culture medium have multiple functions that are essential for fungal fitness and virulence (Fig. 3). Secreted proteins with wall-related functions are required for the constant remodeling of the wall due to morphological adaptations, growth and cell separation, and cell wall repair. This correlates with the high number of peptide identifications in almost all growth
conditions examined. Cht3, Mp65, Scw11, Sim1, Sun41, Tos1, PJ34 HCl and Xog1 were found in every condition tested with ample peptide identifications (Table 1). As they are accessible and abundant, this set of proteins might be used in serological detection of invasive candidiasis, both by direct detection of these proteins in host samples and by detection of antibodies elicited in the host against these proteins (Laín et al., 2008; Ostrosky-Zeichner, 2012). Secreted hydrolytic enzymes generally serve tissue destruction and nutrient acquisition and are therefore closely linked to virulence. Conceivably, they could serve as suitable vaccine targets. Vaccines against Sap2 proved already to be effective against systemic and mucosal infections in mice (Vilanova et al., 2004; Sandini et al., 2011b). In summary, the proteomic analysis of the secretome is still in its infancy. Nonetheless, the importance of the secretome for many functions, especially wall remodeling and nutrient acquisition, is already clear.