title: Effects of iprodione and fludioxonil on glycerol synthesis and hyphal development in Candida albicans.
abstract: We investigated the effects of iprodione and fludioxonil on the pathogenic yeast Candida albicans. Growth of the wild-type IFO1385 strain of C. albicans was inhibited by both fungicides, while Saccharomyces cerevisiae was basically unaffected by them even at a concentration of 25 microg/ml. Both fungicides stimulated glycerol synthesis in C. albicans but not in S. cerevisiae. The antioxidant alpha-tocopherol acetate and the cytochrome P-450 inhibitor piperonyl butoxide antagonized the fungitoxicity of iprodione and fludioxonil in C. albicans. It is known that mutations within the histidine kinase NIK1/OS-1 gene confer resistance to iprodione and fludioxonil in Neurospora crassa, while the fungicide-insensitive S. cerevisiae has only one histidine kinase SLN1 gene in its genome. In contrast, C. albicans has three histidine kinase genes, namely CaSLN1, CaNIK1/COS1, and CaHK1, the null mutants of which were found to impair the hyphal formation. Iprodione and fludioxonil were found to suppress filamentation when the IFO1385 strain was incubated on a solid medium containing fetal bovine serum. These observations suggest that iprodione and fludioxonil interfere with the CaNIK1/COS1 signal transduction pathway, resulting in glycerol synthesis stimulation and the inhibition of hyphal formation.
authors.affiliation: Faculty of Life Science, University of Toyo, Itakura, Oura-gun 374-0193, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ochiai
authors.forename: Makoto
authors.initials: M
authors.lastname: Fujimura
authors.forename: Michiyo
authors.initials: M
authors.lastname: Oshima
authors.forename: Takayuki
authors.initials: T
authors.lastname: Motoyama
authors.forename: Akihiko
authors.initials: A
authors.lastname: Ichiishi
authors.forename: Hisafumi
authors.initials: H
authors.lastname: Yamada-Okabe
authors.forename: Isamu
authors.initials: I
authors.lastname: Yamaguchi
mesh_terms: D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development* / Q000648:ultrastructure; D003470:Culture Media; D004149:Dioxoles / Q000494:pharmacology*; D005659:Fungicides, Industrial / Q000494:pharmacology*; D005990:Glycerol / Q000378:metabolism; D000071677:Histidine Kinase; D006827:Hydantoins; D025301:Hyphae / Q000187:drug effects / Q000254:growth & development* / Q000648:ultrastructure; D008826:Microbial Sensitivity Tests; D010574:Pesticide Synergists / Q000494:pharmacology; D010882:Piperonyl Butoxide / Q000494:pharmacology; D011494:Protein Kinases / Q000096:biosynthesis / Q000235:genetics; D011758:Pyrroles / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D014810:Vitamin E / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D003470:Culture Media; D004149:Dioxoles; D005659:Fungicides, Industrial; D006827:Hydantoins; D010574:Pesticide Synergists; D011758:Pyrroles; D014810:Vitamin E; D000620:Aminoimidazole Carboxamide; D011494:Protein Kinases; D000071677:Histidine Kinase; C108339:fludioxonil; D010882:Piperonyl Butoxide; D005990:Glycerol; C033148:iprodione