Structure, Cellular Distribution, Antigenicity, and Biological Functions of Fonsecaea pedrosoi Ceramide Monohexosides

Abstract

Monohexosylceramides (CMHs, or cerebrosides) have been reported as membrane and cell wall constituents of both pathogenic and nonpathogenic fungi, presenting remarkable differences in their ceramide moiety compared to mammalian CMHs. Current evidence suggests that CMHs are involved in fungal differentiation and growth and contribute to host immune response. Here we describe a structural diversity between cerebrosides obtained from different forms of the human pathogen Fonsecaea pedrosoi. The major CMH species produced by conidial forms displayed the same structure previously demonstrated by our group for mycelia, an N-2-hydroxyhexadecanoyl-1-␤-D-glucopyranosyl-9-methyl-4,8-sphingadienine. However, the major cerebroside species purified from sclerotic cells carries an additional hydroxyl group, bound to its long-chain base. The structural difference between cerebrosides from mycelial and sclerotic cells was apparently not relevant for their antigenicity, since they were both recognized at similar levels by sera from individuals with chromoblastomycosis and a monoclonal antibody to a conserved cerebroside structure. Preincubation of fungal cells with anti-CMH monoclonal antibodies had no effect on the interaction of F. pedrosoi sclerotic cells with murine macrophages. In contrast to what has been described for other fungal species, sclerotic bodies are resistant to the antifungal action of anti-CMH antibodies. Immunofluorescence analysis showed that recognition of sclerotic cells by these antibodies only occurs at cell wall regions in which melanization is not evident. Accordingly, melanin removal with alkali results in an increased reaction of fungal cells with anti-CMH antibodies. Our results indicate that cerebroside expression in F. pedrosoi cells is associated with dimorphism and melanin assembly on the fungal cell wall.

Black Yeasts and Their Filamentous Relatives: Principles of Pathogenesis and Host Defense

“…Likewise, individuals from areas of endemicity with previous exposure to a fungus develop a specific humoral response, although this has not been correlated clearly with the course of the disease (132). Furthermore, antibodies with direct antimicrobial action have been detected in sera of infected individuals (105,133).…”

Chromoblastomycosis

“…Ceramide monohexosides (CMHs) have been identified in membranes and cellular walls of pathogenic and nonpathogenic fungi, presenting a unique ceramide moiety compared to those of mammalian CMHs (177,178). CMHs seem to have a pivotal function in the host immune response, and they may be associated with fungal differentiation.…”

Sphingolipids as Targets for Treatment of Fungal Infections

“…These lipid domains are responsible for compartmentalization of a variety of molecules required for energy production and polysaccharide and sterol metabolism [85], as well as some virulence factors such as phospholipases and superoxide dismutase [75,86]. As a component of lipid domains, GlcCer is present not only in plasma membranes but also in vesicles and the cell wall [72,[87][88][89], suggesting that this molecule is crucial not only for fungal growth but also for secretion processes and cell protection.…”