Figure 3. CaFT Profiling and Characterization of Cerulenin-Induced HI.

(A) CaFT profiles of cerulenin, with highlighted strains as follows: FAS1 (orf19.979), FAS2 (orf19.5949), and MDR1 (orf19.5604). A homozygous deletion of MDR1 is hypersensitive to cerulenin [21]; however, the heterozygous deletion strain showed no specific hypersensitivity at the ICs tested in the CaFT.

(B) The spot tests of selected heterozygous deletion strains against cerulenin. Note that the hypersensitivity of the MDR1 strain was only seen at the highest concentration of cerulenin tested.

(C) A model for regulating stoichiometry of the FAS complex in S. cerevisiae. As shown by Wenz et al. [20], the expression of ScFAS2 is repressed by an unknown transcription repressor (rep. X), which is in turn derepressed by free β subunit (Fas1p). According to this model, ScFAS2 expression is dependent on free Fas1p to control the normal stoichiometry of the FAS complex. A similar regulatory mechanism in C. albicans may explain the observed cerulenin-induced HI of FAS1 but not FAS2 (see text for details).

(D) FAS1 is haploinsufficient under the standard growth conditions. In order to determine HI, cultures of the selected strains were first incubated for 6 h (reaching exponential growth) and then diluted to an OD₆₀₀ of 0.005. The fresh cultures were incubated for another 12 h, after which the OD was monitored for an additional 4 h.