Molecular organization of the cell wall ofCandida albicansand its relation to pathogenicity

Abstract

Candida albicans is one of the most important opportunistic pathogenic fungi. Weakening of the defense mechanisms of the host, and the ability of the microorganism to adapt to the environment prevailing in the host tissues, turn the fungus from a rather harmless saprophyte into an aggressive pathogen. The disease, candidiasis, ranges from light superficial infections to deep processes that endanger the life of the patient. In the establishment of the pathogenic process, the cell wall of C. albicans (as in other pathogenic fungi) plays an important role. It is the outer structure that protects the fungus from the host defense mechanisms and initiates the direct contact with the host cells by adhering to their surface. The wall also contains important antigens and other compounds that affect the homeostatic equilibrium of the host in favor of the parasite. In this review, we discuss our present knowledge of the structure of the cell wall of C. albicans, the synthesis of its different components, and the mechanisms involved in their organization to give rise to a coherent composite. Furthermore, special emphasis has been placed on two further aspects: how the composition and structure of C. albicans cell wall compare with those from other fungi, and establishing the role of some specific wall components in pathogenesis. From the data presented here, it becomes clear that the composition, structure and synthesis of the cell wall of C. albicans display both subtle and important differences with the wall of different saprophytic fungi, and that some of these differences are of utmost importance for its pathogenic behavior.

Candida albicansCell Wall Proteins

“…Electron microscopy of thin sections of the C. albicans cell wall shows layers which appear to be derived from differential abundances of cell wall constituents (177,179,322). The number of layers observed is variable and seems to be related to both strains and methodology (reviewed in reference 49).…”

“…Thus, synthesis, remodeling, and hydrolysis must be coordinated in time and space to provide integrity, flexibility, and cell separation. Structural rigidity, thus maintaining shape, is conferred by polysaccharides, and the synthesis of polysaccharides has recently been reviewed (204,322). Enzymes localized in the membrane synthesize the chitin and ␤-1,3-glucan.…”

“…During this decade, there have been multiple reviews on various aspects of the C. albicans cell surface, including several very recently (100,101,116,187,215,246,312,322,355,381). The proteins of the cell wall may play a role in maintaining structural integrity and in mediating adherence, whether to host or microbes, or they may have enzymatic functions, e.g., proteolysis.…”

Resistance to echinocandin-class antifungal drugs

“…Maintenance of fungal cell wall integrity is essential, as fungi cannot survive without this structure or even if it is markedly altered in some way. The wall is an extracellular matrix with a layered organization consisting of an outer layer of glycoproteins and an inner layer of carbohydrate polymers including glucan, chitin and galactomannan (Latge et al, 2005;Douglas, 2006;Ruiz-Herrera et al, 2006). In saprophytic and pathogenic fungi, the carbohydrate layer is comprised mainly of β-1,3-glucan and α-1,3-glucan, but it also contains some β-1,6-glucan and chitin.…”

Evidence for the presence of proteolytically active secreted aspartic proteinase 1 of Candida parapsilosis in the cell wall

“…The temporarily cell wall associated proteins and noncovalently linked proteins can be released from the yeast cell wall by ionic detergents or chaotropic agents. 19,20 In addition, the extraction of cell wall fractions with a reducing agent such as b-mercaptoethanol (bME) leads to release of a distinct set of proteins, which might be bound to other cell wall proteins by disulfide bridges. 21,22 In this study, we show that Sapp1p is temporarily retained in the cell wall prior to secretion into the extracellular space.…”