Candida albicans is a major cause of
oropharyngeal, vulvovaginal and haematogenously disseminated
candidiasis.
Endocytosis of C.
albicans hyphae by
host cells is a prerequisite for tissue invasion. This internalization involves interactions between the
fungal invasin Als3 and host E- or
N-cadherin. Als3 shares some structural similarity with InlA, a major invasion protein of the
bacterium Listeria monocytogenes. InlA mediates entry of
L. monocytogenes into
host cells through binding to
E-cadherin. A role in internalization, for a non-classical stimulation of the
clathrin-dependent endocytosis machinery, was recently highlighted. Based on the similarities between the C.
albicans and
L. monocytogenes invasion proteins, we studied the role of
clathrin in the internalization of C.
albicans. Using live-cell imaging and indirect
immunofluorescence of
epithelial cells infected with C.
albicans, we observed that host
E-cadherin,
clathrin,
dynamin and
cortactin accumulated at sites of C.
albicans internalization. Similarly, in
endothelial cells, host
N-cadherin,
clathrin and
cortactin accumulated at sites of
fungal endocytosis. Furthermore,
clathrin,
dynamin or
cortactin depletion strongly inhibited C.
albicans internalization by
epithelial cells. Finally,
beads coated with Als3 were internalized in a clathrin-dependent manner. These data indicate that C.
albicans, like
L. monocytogenes, hijacks the clathrin-dependent endocytic machinery to invade
host cells.
