Impact of Candida albicans NDT80 and UME6 on biofilm formation and fluconazole susceptibility

Second, what is the genetic interaction between NDT80 and UME6? We find that Ndt80 is required for filamentation and biofilm formation in five clinical isolates in addition to the reference strain SC5314, where Ndt80 function has been well established. RNA-sequencing (RNA-seq) data indicate that UME6 RNA levels are reduced in an ndt80Δ/Δ mutant, possibly a result of altered RME1 and WOR1 expression, both of which control UME6.

Increased expression of UME6 in ndt80Δ/Δ mutants of three strain backgrounds restores filamentation and biofilm formation, though RNA-seq assays indicate that it does not suppress the overall ndt80Δ/Δ gene expression defect. Ndt80 has a second role in promoting tolerance to the antifungal drug fluconazole, an inhibitor of ergosterol synthesis. Increased expression of UME6 in ndt80Δ/Δ mutants enhances their susceptibility to fluconazole.

Therefore, our results show an unexpected relationship between Ume6 expression and azole drug sensitivity. To our knowledge Ume6 has previously been known to function only in filamentation and biofilm formation.