Abstract
Sphingolipids are involved in several cellular functions, including maintenance of cell wall integrity. To gain insight into the role of individual genes of sphingolipid biosynthetic pathway, we have screened Saccharomyces cerevisiae strains deleted in these genes for sensitivity to cell wall perturbing agents calcofluor white and congo red. Only deletants of FEN1 and SUR4 genes were found to be sensitive to both these agents. Candida albicans strains deleted in their orthologs, CaFEN1 and CaFEN12, respectively, also showed comparable phenotypes, and a strain deleted for both these genes was extremely sensitive to cell wall perturbing agents. Deletion of these genes was reported earlier to sensitise cells to amphotericin B (AmB), which is a polyene drug that kills the cells mainly by binding and sequestering ergosterol from the plasma membrane. Here we show that their AmB sensitivity is likely due to their cell wall defect. Further, we show that double deletant of C. albicans is defective in hyphae formation as well as biofilm development. Together this study reveals that deletion of FEN1 and SUR4 orthologs of C. albicans leads to impaired cell wall integrity and biofilm formation, which in turn sensitise cells to AmB.
Highlights
Candida albicans, an opportunistic pathogen of humans, can cause infections ranging from superficial skin infections to life-threatening invasive infections[1,2]
Deletants of FEN1 and SUR4 genes of S. cerevisiae and their orthologs in C. albicans are impaired in cell wall integrity
calcofluor white (CFW) sensitivity of FEN1 deletant was reported earlier, after being identified through a screen for genetic interaction with CCW12, a gene involved in CWI39
Summary
An opportunistic pathogen of humans, can cause infections ranging from superficial skin infections to life-threatening invasive infections[1,2]. First, we have screened deletion mutants of sphingolipid biosynthetic pathway genes of S. cerevisiae with cell wall perturbing agents calcofluor white (CFW) and congo red (CR) and found that only deletants of FEN1 and SUR4 genes were sensitive to both the chemicals. C. albicans strain deleted in both these genes was found to be defective in hyphae formation and biofilm development.
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