title: ECM17-dependent methionine/cysteine biosynthesis contributes to biofilm formation in Candida albicans.
abstract: Candida albicans has become the fourth leading pathogen of nosocomial bloodstream infections largely due to biofilm formation on implanted medical devices. Previous microarray data indicated that almost all genes in methionine (Met)/cysteine (Cys) biosynthesis pathway were up-regulated during biofilm formation, especially during the adherence period. In this work, we studied the role of Met/Cys biosynthesis pathway by disrupting ECM17, a gene encoding sulfite reductase in C. albicans. It was found that the ecm17Δ/Δ mutant failed to catalyze the biochemical reaction from sulfite to H(2)S and hardly grew in media lacking Met and Cys. NaSH, the donor of H(2)S, dose-dependently improved the growth of ecm17Δ/Δ in media lacking a sulfur source. Sufficient Met/Cys supply inhibited the expression of ECM17 in a dose-dependent manner. These results validated the important role of ECM17 in Met/Cys biosynthesis. Interestingly, the ecm17Δ/Δ mutant showed diminished ability to form biofilm, attenuated adhesion on abiotic substrate and decreased filamentation on solid SLD medium, especially under conditions lacking Met/Cys. Further results indicated that ECM17 affected the expressions of ALS3, CSH1, HWP1 and ECE1, and that the cAMP-protein kinase A (PKA) pathway was associated with ECM17 and Met/Cys biosynthesis pathway. These results provide new insights into the role of Met/Cys biosynthesis pathway in regulating cAMP-PKA pathway and benefiting biofilm formation.
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: De-Dong
authors.initials: DD
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Bao-Di
authors.initials: BD
authors.lastname: Dai
authors.forename: Xing-Xing
authors.initials: XX
authors.lastname: Li
authors.forename: Lan-Xue
authors.initials: LX
authors.lastname: Zhao
authors.forename: Yong-Bing
authors.initials: YB
authors.lastname: Cao
authors.forename: Lan
authors.initials: L
authors.lastname: Yan
authors.forename: Yuan-Ying
authors.initials: YY
authors.lastname: Jiang
mesh_terms: D018441:Biofilms / Q000254:growth & development*; D002176:Candida albicans / Q000201:enzymology* / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion; D003470:Culture Media / Q000737:chemistry; D003545:Cysteine / Q000096:biosynthesis*; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D055786:Gene Knockout Techniques; D006862:Hydrogen Sulfide / Q000378:metabolism; D025301:Hyphae / Q000254:growth & development; D008715:Methionine / Q000096:biosynthesis*; D050864:Sulfite Reductase (NADPH) / Q000235:genetics / Q000378:metabolism*; D013447:Sulfites / Q000378:metabolism
chemical_list: D003470:Culture Media; D013447:Sulfites; D008715:Methionine; D050864:Sulfite Reductase (NADPH); D003545:Cysteine; D006862:Hydrogen Sulfide