Adhesion, invasion and damage potential was determined for each mutant and normalized against the relevant wild type. Group 2a mutants showed reduced adhesion, invasion and damage. The group 2b mutants efg1Δ and ecm33Δ show significant reduction in adhesion, but have a further decreased ability to invade into epithelial cells, suggesting distinct adhesion and invasion functions of these genes. The group 3 mutant pmt2Δ/PMT2 lacks factors or activities which are specifically associated with invasion and damage, but not adhesion. Group 4 mutants lacking MKC1, GPP1, GPD2 and EED1 showed significant reduction in damage, but not adhesion and invasion. Group 5 mutants lacking CKA2, BCR1, HWP1, BUD2 or RSR1 showed significant reduction in adhesion and damage, but not invasion. n. d.  =  not determined; */**, significant difference compared to the corresponding wild type (WT) (p<0.05/p<0.01). Note that adhesion, invasion and damage assays were performed separately.

Oral TR146 epithelial cells were co-incubated with 10⁵ C. albicans cells for either 20, 60, 120, or 180 min. After extensive washing and fixation, the samples were stained and the adherent cells were counted under the fluorescence microscope. The experiment was performed at least three times in duplicates. The values are calculated as percentage of adherent cells compared to wild type adherent cells at 180 min (100%). */**, significant difference compared to the adhesion of the corresponding WT to oral epithelial cells (p<0.05/p<0.01).

C. albicans cells (wild type and rsr1Δ, bud2Δ, hwp1Δ, bcr1Δ, cka2Δ, eed1Δ, gpp1Δ, gpd2Δ and mkc1Δ) were co-incubated with Caco-2 enterocytes for 3 h. After fixation the samples were differentially stained and analyzed under the fluorescence microscope. The experiment was performed at least three times in duplicates. */**, significant difference compared to the corresponding WT invasion (control) (p<0.05/p<0.01).

(A) Venn diagram showing the distribution of the differentially regulated genes from C. albicans cells grown on epithelial monolayer at 20, 60 and 180 min after horizontal analysis as compared to plastic. (B) Hierarchical clustering of C. albicans genes expressed at 20, 60 and 180 min incubation on oral epithelial cells versus plastic. Gene expression is shown in a logarithmic color range from −11.31 in blue to 11.31 in red. Non regulated genes (1) are shown in yellow. The profiles of the earliest time points cluster more distant to the later time points. The expression profiles of C. albicans exposed to epithelial cells at 20, 60 and 180 min did not show any clear similarities. In contrast, the profiles of cells exposed to plastic for 60 and 180 min were most similar to each other as compared to all other samples.

C. albicans mutant strains lacking ICL1 and PGA34 showed wild type levels of adhesion and/or invasion. However, icl1Δ showed significantly reduced invasion and damage and pga34Δ showed significantly reduced damage. The values are calculated as percentage of adherent/invasive cells or damage compared to the corresponding wild type (100%). **, significant difference compared to the corresponding wild type (WT) (p<0.01).