Mannan Adhesins of Candida albicans: Characterization and Pathogenetic Implications

Abstract

The ability of Candida albicans to adhere to host tissue may well represent an important virulence trait of this opportunistic fungal pathogen. The initiation of lesions at specific tissue locations in the host appears due to specific adherence interactions between adhesins of C. albicans and host cell surface ligands. We and others have found that adhesins appear associated with the phosphomannoprotein of the candidal cell surface. Hydrophilic yeast cells specifically attach to mouse splenic marginal zone macrophages via adhesins that are associated with the glycan portion of the phosphomannoprotein complex. Treatment of yeast cells with β-mercaptoethanol causes release of the fungal adhesin. The adhesin activity is preserved following boiling or digestion with proteolytic enzymes, but is lost following α-mannosidase digestion or periodate oxidation, thus giving support to the mannan nature of the adhesin (s). Hydrolysis of the mannan adhesins by 10mM HCl yields acid-stable and acidlabile moieties, and adhesin sites are associated with both moieties. Adhesin activity in the acid-stable part appears to involve the α-1, 6-linked mannose backbone and the α-1, 2-linked mannosyl side chains. In the acid-labile portion, a β-1, 2-linked tetramannose side-chain shows strong adhesin activity. In related work, we found that specific elimination of macrophages results in increased susceptibility of mice to disseminated candidiasis. In addition, mice induced to make an antibody response against the adhesin preparation are more resistant to disease. Our results indicate that macrophages are important in host resistance against disseminated candidiasis, and we speculate that antibodies specific for mannan adhesins aid in host resistance.