title: Critical role for CaFEN1 and CaFEN12 of Candida albicans in cell wall integrity and biofilm formation.
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.
authors.affiliation: CSIR-Institute of Microbial Technology, Sector 39-A, Chandigarh-160 036, India.
authors.forename: Md
authors.initials: M
authors.lastname: Alfatah
authors.affiliation: CSIR-Institute of Microbial Technology, Sector 39-A, Chandigarh-160 036, India.
authors.forename: Vinay K
authors.initials: VK
authors.lastname: Bari
authors.affiliation: CSIR-Institute of Microbial Technology, Sector 39-A, Chandigarh-160 036, India.
authors.forename: Anubhav S
authors.initials: AS
authors.lastname: Nahar
authors.affiliation: CSIR-Institute of Microbial Technology, Sector 39-A, Chandigarh-160 036, India.
authors.forename: Swati
authors.initials: S
authors.lastname: Bijlani
authors.affiliation: CSIR-Institute of Microbial Technology, Sector 39-A, Chandigarh-160 036, India.
authors.forename: K
authors.initials: K
authors.lastname: Ganesan
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development*; D053898:Biosynthetic Pathways / Q000235:genetics; D002176:Candida albicans / Q000166:cytology / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D005800:Genes, Fungal; D025301:Hyphae / Q000187:drug effects / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D012441:Saccharomyces cerevisiae / Q000235:genetics; D013107:Sphingolipids / Q000096:biosynthesis
chemical_list: D005656:Fungal Proteins; D013107:Sphingolipids; D000666:Amphotericin B