A model for transepithelial migration of human fungal pathogens was establi
shed, in which Candida albicans was shown to migrate across a monolayer of
Caco-2 intestinal cells in a two-chamber system. Electron microscopy reveal
ed typical stages of epithelial penetration by C. albicans including phagoc
ytosis at the apical side, intra- and intercellular migration and exit on t
he basolateral side of the monolayer. Hyphal growth forms appeared particul
arly involved in penetration of the Caco-2 monolayer. The model was examine
d using defined C, albicans mutants defective in hyphal development (efg1/e
fg1) or growth (ura3/ura3). Transmigration of the efg1/efg1 mutant strain w
as reduced, while transmigration of the ura3/ura3 strain was blocked comple
tely in the absence of uridine. Because these results parallel virulence ch
aracteristics of the mutants the Caco-2 monolayer system appears a useful m
odel for the study of fungal-human host cell interactions.