Candida albicans Als3, a multifunctional adhesin and invasin

Abstract

Candida albicans is part of the normal human flora, and it grows on mucosal surfaces in healthy individuals. In susceptible hosts, this organism can cause both mucosal and hematogenously disseminated disease. For C. albicans to persist in the host and induce disease, it must be able to adhere to biotic and abiotic surfaces, invade host cells, and obtain iron. The C. albicans hypha-specific surface protein Als3 is a member of the agglutinin-like sequence (Als) family of proteins and is important in all of these processes. Functioning as an adhesin, Als3 mediates attachment to epithelial cells, endothelial cells, and extracellular matrix proteins. It also plays an important role in biofilm formation on prosthetic surfaces, both alone and in mixed infection with Streptococcus gordonii. Als3 is one of two known C. albicans invasins. It binds to host cell receptors such as E-cadherin and N-cadherin and thereby induces host cells to endocytose the organism. Als3 also binds to host cell ferritin and enables C. albicans to utilize this protein as a source of iron. Because of its multiple functions and its high expression level in vivo, Als3 is a promising target for vaccines that induce protective cell-mediated and antibody responses. This review will summarize the multiple functions of this interesting and multifunctional protein.

Figures

Fig. 1.

Sequence homology among members of the Als family of proteins. Numbers indicate percent identity at the amino acid level.

Fig. 2.

Schematic diagram of the structure of Als3.

Fig. 3.

Diagram of the transcriptional regulation of ALS3 expression. A1 and A2 are activation regions in the promoter of ALS3, and R1 and R2 are repressor regions. Data are from references and .

Fig. 4.

Three-dimensional models of the N-terminal region of Als3 binding to the extracellular domains of E-cadherin and N-cadherin. The solvent-accessible surface areas of the proteins are shown, and the β-barrel domains are numbered sequentially from the N terminus. In models of the docking of Als3 to a cadherin (left column), the Als protein is blue and the cadherin is gold. In models of cadherin self-association (right column), one cadherin molecule is blue and the other cadherin is gold. (Reprinted from Phan et al. [47].)