Hyphal induction in the human fungal pathogen Candida albicans reveals a characteristic wall protein profile

Abstract

The ability of Candida albicans to switch from yeast to hyphal growth is essential for its virulence. The walls and especially the covalently attached wall proteins are involved in the primary host-pathogen interactions. Three hyphal induction methods were compared, based on fetal calf serum, the amino sugar N-acetylglucosamine (GlcNAc) and the mammalian cell culture medium Iscove's modified Dulbecco's medium (IMDM). GlcNAc and IMDM were preferred, allowing stable hyphal growth over a prolonged period without significant reversion to yeast growth and with high biomass yields. We employed Fourier transform-MS combined with a 15 N-metabolically labelled reference culture as internal standard for relative quantification of changes in the wall proteome upon hyphal induction. A total of 21 wall proteins were quantified. Our induction methods triggered a similar response characterized by (i) a category of wall proteins showing strongly increased incorporation levels (Als3, Hwp2, Hyr1, Plb5 and Sod5), (ii) another category with strongly decreased levels (Rhd3, Sod4 and Ywp1) and (iii) a third one enriched for carbohydrateactive enzymes (including Cht2, Crh11, Mp65, Pga4, Phr1, Phr2 and Utr2) and showing only a limited response. This is, to our knowledge, the first systematic, quantitative analysis of the changes in the wall proteome of C. albicans upon hyphal induction. Finally, we propose new wall-protein-derived candidates for vaccine development.

Surface Stress Induces a Conserved Cell Wall Stress Response in the Pathogenic Fungus Candida albicans

“…Reinforcement of the cell wall in response to antifungal stresses is well described, especially with respect to an increase in chitin content as a result of increased chitin synthesis (11,12). The cell wall proteome itself is highly dynamic (13) and adaptable in response to external conditions (14,15) as well as morphological changes (16).…”

Ras Signaling Gets Fine-Tuned: Regulation of Multiple Pathogenic Traits of Candida albicans

“…Ras signaling is linked to cell adhesion through its role in regulating both filamentous growth and biofilm formation, likely through the activation of Efg1 and Tec1 (and Bcr1 during biofilm formation), which control the expression of genes involved in cell adhesion (59)(60)(61). During both biofilm formation and filamentous growth, the genes from the ALS (agglutinin-like sequence) adhesin gene family are highly induced (62). This family, and Als3 in particular, is involved in cell adhesion and mediates attachment to endothelial cells (63), epithelial cells, and extracellular matrix proteins (64).…”

Vaccination with Recombinant Non-transmembrane Domain of Protein Mannosyltransferase 4 Improves Survival during Murine Disseminated Candidiasis

“…Most virulence factors, including adhesion, invasion, and yeast-to-hypha transition, localize on the cell wall, such as Pga4p, Pga7p, Alg2p, Pmt4p, Mnn46p, Iff11p. [21][22][23][24][25][26][27][28] The cell wall also plays an important role in crucial host-fungus interactions that facilitate the establishment of human mycoses. Thus the cell wall proteins might be ideal vaccine targets to induce protective immune response in host.…”