title: Small-molecule inhibitors of biofilm formation in laboratory and clinical isolates of Candida albicans.
abstract: Candida albicans cells have the ability to form biofilms on biotic and abiotic surfaces, such as indwelling medical devices. C. albicans cells can interconvert between budded and hyphal growth forms, herein termed the budded-to-hyphal transition (BHT), which is important for the formation of mature biofilms. Previous work identified 23 small organic molecules that could inhibit the BHT but did not affect C. albicans cell viability or budded cell growth. These BHT inhibitors were proposed to inhibit multiple signalling pathways regulating the BHT, many of which also regulate biofilm formation. However, only three of the BHT inhibitors, buhytrinA, ETYA and CGP-37157, were capable of inhibiting in vitro biofilm formation of wild-type laboratory C. albicans strains. When clinical C. albicans isolates were examined for their ability to form biofilms, only 11 of the 28 clinical isolates tested (39%) were capable of forming biofilms. Although buhytrinA, ETYA and CGP-37157 could inhibit the BHT of all 28 clinical isolates, they were only able to inhibit biofilm formation of a subset of these clinical isolates, with ETYA having 100% efficacy. These data indicate that the biofilm-forming capability of laboratory and clinical isolates of C. albicans, as well as the efficacy of BHT inhibitors against these different isolates, can differ dramatically. These differences between laboratory and clinical isolates should be an important aspect to consider when examining potentially new antifungal therapeutics.
authors: Department of Microbiology and Molecular Genetics, University of Vermont, 202 Stafford Hall, 95 Carrigan Drive, Burlington, VT 05405, USA.
authors: Ariel
authors: A
authors: Grald
authors: Department of Microbiology and Molecular Genetics, University of Vermont, 202 Stafford Hall, 95 Carrigan Drive, Burlington, VT 05405, USA.
authors: Philip
authors: P
authors: Yargosz
authors: Department of Microbiology and Molecular Genetics, University of Vermont, 202 Stafford Hall, 95 Carrigan Drive, Burlington, VT 05405, USA.
authors: Samantha
authors: S
authors: Case
authors: Department of Microbiology and Molecular Genetics, University of Vermont, 202 Stafford Hall, 95 Carrigan Drive, Burlington, VT 05405, USA.
authors: Katelyn
authors: K
authors: Shea
authors: Department of Microbiology and Molecular Genetics, University of Vermont, 202 Stafford Hall, 95 Carrigan Drive, Burlington, VT 05405, USA.
authors: Douglas I
authors: DI
authors: Johnson
mesh_terms: D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification / Q000502:physiology; D002177:Candidiasis / Q000382:microbiology; D002998:Clonazepam / Q000031:analogs & derivatives* / Q000494:pharmacology; D003470:Culture Media; D006801:Humans; D025301:Hyphae / Q000187:drug effects / Q000502:physiology; D008826:Microbial Sensitivity Tests; D015398:Signal Transduction / Q000187:drug effects; D013841:Thiazepines / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D003470:Culture Media; D013841:Thiazepines; D015117:5,8,11,14-Eicosatetraynoic Acid; D002998:Clonazepam; C079032:CGP 37157