José L Là pez-Ribot

Candida albicans biofilms are structured microbial communities composed of a mixture of yeast cells and hyphal elements, suggesting a pivotal role for the dimorphic switch in the development of biofilms. We have used C. albicans mutants defective in genes involved in filamentation (Deltacph1, Deltaefg1, Deltahst7, and Deltacst20) and compared these mutants to wild-type strains to determine whether filamentation is an integral factor for biofilm formation. Scanning electron microscopy revealed that Deltacph1, Deltahst7 and Deltacst20 mutants were able to filament and form structured biofilms displaying three-dimensional architecture similar to those formed by wild-type strains. However, Deltaefg1 and Deltacph1/Deltaefg1 mutants were unable to filament and did not form biofilms, but rather sparse monolayers of loosely attached elongated, rod-like, cells. Antimicrobial susceptibility testing showed intrinsic resistance of all mutant strains to fluconazole and amphotericin B when attached to the surface of biomaterials. These results suggest that hyphal formation is pivotal for biofilm development in C. albicans. However, the sessile lifestyle associated with adherent cells confers antifungal resistance, regardless of coherent biofilm formation.

The cell wall of Candida albicans is not only the structure where many essential biological functions reside but is also a significant source of candidal antigens. The major cell wall components that elicit a response from the host immune system are proteins and glycoproteins, the latter being predominantly mannoproteins. Both carbohydrate and protein moieties are able to trigger immune responses. Proteins and glycoproteins exposed at the most external layers of the wall structure are involved in several types of interactions of fungal cells with the exocellular environment. Thus, coating of fungal cells with host antibodies has the potential to profoundly influence the host-parasite interaction by affecting antibody-mediated functions such as opsonin-enhanced phagocytosis and blocking the binding activity of fungal adhesins to host ligands. In this review we examine various members of the protein and glycoprotein fraction of the C. albicans cell wall that elicit an antibody response in vivo. Some of the studies demonstrate that certain cell wall antigens and anti-cell wall antibodies may be the basis for developing specific and sensitive serologic tests for the diagnosis of candidiasis, particularly the disseminated form. In addition, recent studies have focused on the potential of antibodies against the cell wall protein determinants in protecting the host against infection. Hence, a better understanding of the humoral response triggered by the cell wall antigens of C. albicans may provide the basis for the development of (i) effective procedures for the serodiagnosis of disseminated candidiasis, and (ii) novel prophylactic (vaccination) and therapeutic strategies to control this type of infections.

Immunoscreening of a Candida albicans expression library with antibodies against the 58 kDa fibrinogen-binding mannoprotein (mp58) of the fungus resulted in the isolation of clones encoding the protein moiety of this molecule. Sequence of the 0.9 kb cDNA of one of the clones selected for further analysis, revealed an open reading frame coding for 292 amino acids, which displays sequence similarity to proteins belonging to a family of immunodominant antigens of Aspergillus spp. The gene corresponding to this cDNA was named FBP1 (fibrinogen-binding protein). These results represent the first report on the identification of C. albicans genes encoding surface receptors for host proteins.