title: Serum cholesterol promotes the growth of Candida glabrata in the presence of fluconazole.
abstract: The pathogenic fungus Candida glabrata is thought to utilize extracellular sterols during infection, but there have been few reports on the sterol uptake mechanisms of this fungus. The addition of serum promoted the growth of C. glabrata cells in the presence of the sterol inhibitor fluconazole, probably as the result of incorporation of cholesterol from serum. We demonstrated that lipoprotein-deficient serum, in which most of the cholesterol was eliminated, could not rescue the growth of fluconazole-treated C. glabrata cells, but it successfully promoted the expression of the sterol transporter gene AUS1. After supplementation of free cholesterol to lipoprotein-deficient serum, the serum was again competent to promote the growth of fluconazole-treated C. glabrata. The serum-mediated growth rescue from fluconazole inhibition was observed in the nonpathogenic yeast Saccharomyces cerevisiae when it was followed by the activation of anaerobic sterol uptake. These results suggested that serum cholesterol was incorporated into yeast cells to compensate for sterol depletion when sterol uptake was activated. The uptake of serum cholesterol could support the growth of C. glabrata cells during bloodstream infections.
authors.affiliation: Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo, 162-8640, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Nagi
authors.forename: Koichi
authors.initials: K
authors.lastname: Tanabe
authors.forename: Hironobu
authors.initials: H
authors.lastname: Nakayama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamagoe
authors.forename: Takashi
authors.initials: T
authors.lastname: Umeyama
authors.forename: Takahiro
authors.initials: T
authors.lastname: Oura
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ohno
authors.forename: Susumu
authors.initials: S
authors.lastname: Kajiwara
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Miyazaki
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000935:Antifungal Agents / Q000378:metabolism / Q000494:pharmacology*; D041221:Candida glabrata / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D002784:Cholesterol / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology*; D015725:Fluconazole / Q000378:metabolism / Q000494:pharmacology*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D013261:Sterols / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D000935:Antifungal Agents; D005656:Fungal Proteins; D013261:Sterols; D015725:Fluconazole; D002784:Cholesterol