Candida albicans internalization by host cells is mediated by a clathrin-dependent mechanism.
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.
Institut Pasteur, Unité Biologie et Pathogénicité Fongiques, F-75015 Paris, France.
Emilia
E
Moreno-Ruiz
Marta
M
Galán-Díez
Weidong
W
Zhu
Elena
E
Fernández-Ruiz
Christophe
C
d'Enfert
Scott G
SG
Filler
Pascale
P
Cossart
Esteban
E
Veiga
D015820:Cadherins / Q000378:metabolism; D002176:Candida albicans / Q000166:cytology / Q000378:metabolism* / Q000472:pathogenicity; D002177:Candidiasis / Q000378:metabolism* / Q000382:microbiology; D002966:Clathrin / Q000378:metabolism*; D051356:Cortactin / Q000378:metabolism; D034281:Dynamins / Q000378:metabolism; D004705:Endocytosis; D004847:Epithelial Cells / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D025301:Hyphae / Q000166:cytology / Q000378:metabolism; D018613:Microscopy, Confocal; D014774:Virulence
C113620:ALS3 protein, Candida albicans; D015820:Cadherins; D002966:Clathrin; D051356:Cortactin; D005656:Fungal Proteins; D034281:Dynamins