title: Polyketide glycosides from Bionectria ochroleuca inhibit Candida albicans biofilm formation.
abstract: One of the challenges presented by Candida infections is that many of the isolates encountered in the clinic produce biofilms, which can decrease these pathogens' susceptibilities to standard-of-care antibiotic therapies. Inhibitors of fungal biofilm formation offer a potential solution to counteracting some of the problems associated with Candida infections. A screening campaign utilizing samples from our fungal extract library revealed that a Bionectria ochroleuca isolate cultured on Cheerios breakfast cereal produced metabolites that blocked the in vitro formation of Candida albicans biofilms. A scale-up culture of the fungus was undertaken using mycobags (also known as mushroom bags or spawn bags), which afforded four known [TMC-151s C-F (1-4)] and three new [bionectriols B-D (5-7)] polyketide glycosides. All seven metabolites exhibited potent biofilm inhibition against C. albicans SC5314, as well as exerted synergistic antifungal activities in combination with amphotericin B. In this report, we describe the structure determination of the new metabolites, as well as compare the secondary metabolome profiles of fungi grown in flasks and mycobags. These studies demonstrate that mycobags offer a useful alternative to flask-based cultures for the preparative production of fungal secondary metabolites.
authors.affiliation: Natural Product Discovery Group, Institute for Natural Products Applications and Research Technologies, and ‡Department of Chemistry & Biochemistry, Stephenson Life Science Research Center, University of Oklahoma , 101 Stephenson Parkway, Norman, Oklahoma 73019, United States.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Jianlan
authors.initials: J
authors.lastname: You
authors.forename: Jarrod B
authors.initials: JB
authors.lastname: King
authors.forename: Shengxin
authors.initials: S
authors.lastname: Cai
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Park
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Powell
authors.forename: Robert H
authors.initials: RH
authors.lastname: Cichewicz
mesh_terms: D018441:Biofilms / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects*; D006027:Glycosides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D009825:Oklahoma; D061065:Polyketides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D012988:Soil Microbiology
chemical_list: D006027:Glycosides; D061065:Polyketides