Covalently linked cell wall proteins ofCandida albicans  and their role in fitness and virulence

Abstract

The cell wall of Candida albicans consists of an internal skeletal layer and an external protein coat. This coat has a mosaic-like nature, containing c. 20 different protein species covalently linked to the skeletal layer. Most of them are GPI proteins. Coat proteins vary widely in function. Many of them are involved in the primary interactions between C. albicans and the host and mediate adhesive steps or invasion of host cells. Others are involved in biofilm formation and cell-cell aggregation. They further include iron acquisition proteins, superoxide dismutases, and yapsin-like aspartic proteases. In addition, several covalently linked carbohydrate-active enzymes are present, whose precise functions remain hitherto largely elusive. The expression levels of the genes that encode covalently linked cell wall proteins (CWPs) can vary enormously. They depend on the mode of growth and the combined inputs of several signaling pathways that sense environmental conditions. This is reflected in the unusually long intergenic regions of most of these genes. Finally, the precise location of several covalently linked CWPs is temporally and spatially regulated. We conclude that covalently linked CWPs of C. albicans play a crucial role in fitness and virulence and that their expression is tightly controlled.

A Domain-Centric Analysis of Oomycete Plant Pathogen Genomes Reveals Unique Protein Organization

“…The N-terminal DUF2403 contains a Glyrich region without further functional annotation, whereas five highly conserved Cys residues characterize the C-terminal DUF2401. Proteins containing both DUFs have been characterized in S. cerevisiae and in Candida albicans as being covalently linked to the cell wall (Terashima et al, 2002;Yin et al, 2005;Klis et al, 2009). Another overrepresented DUF within plant pathogens and mainly found in oomycetes is DUF953 (IPR010357).…”

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

“…Most of these proteins are only expressed under specific conditions and our previous work suggests that there are no more than approximately 20-30 wall proteins expressed at any given time . GPI wall proteins generally show a modular structure with an N-terminal conserved domain followed by a highly O-glycosylated serine-and threonine-(S/T)-rich domain that can also include a repeat region (Klis et al, 2009). In particular, mannosylation of wall proteins is important for limiting wall porosity and might play a role in b-glucan masking (Wheeler et al, 2008).…”

N-Acetyl-d-glucosaminylphosphatidylinositol De-N-acetylase from Entamoeba histolytica

“…GPI anchoring of cell surface proteins to the membrane is particularly important in eukaryotes, and defects in GPI anchor biosynthesis can affect function as well as the viability of the cells (4). Thus, the GPI biosynthetic pathway is an important therapeutic target, provided the species-specific differences of this pathway can be appropriately exploited.…”

“…3 Present address: Post Doctoral Fellow at The Institute for Biomedical Engineering at the ETH, 8092 Zurich, and The University of Zurich, 8001 Zurich, Switzerland. 4 To whom correspondence should be addressed. Tel.…”