title: In vitro effect of DNA topoisomerase inhibitors on Candida albicans.
abstract: In this study we investigated the in vitro antifungal activity of 10 DNA topoisomerase inhibitors on the growth of Candida albicans. The EUCAST broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of the compounds for C. albicans. In addition, the effect of the inhibitors on the growth mode of C. albicans was investigated by light microscopy imaging. Of the 10 DNA topoisomerase inhibitors tested, only the anti-cancer drug aclarubicin displayed antifungal activity with a determinable MIC value of 8.4 microg/ml (10.3 microM). Aclarubicin was also active against clinical isolates of C. albicans with MIC values ranging between 0.8 and 7.3 microg/ml (1-9 microM). Vitality assays showed that the action of aclarubicin was fungistatic. Four other DNA topoisomerase inhibitors, daunorubicin, doxorubicin, idarubicin and beta-lapachone, affected the morphology of C. albicans. The first three inhibitors encouraged the fungus to grow predominantly in the yeast form, whereas beta-lapachone caused hyphal proliferation. The results of this study indicate that some DNA topoisomerase inhibitors effect the growth and morphology of C. albicans suggesting a possible role as antifungal agents in the treatment of C. albicans infections.
authors.affiliation: BioMedical Research Centre, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich.
authors.forename: Shing C
authors.initials: SC
authors.lastname: Kwok
authors.forename: Silke
authors.initials: S
authors.lastname: Schelenz
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.forename: Dietmar
authors.initials: D
authors.lastname: Steverding
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005656:Fungal Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D025301:Hyphae / Q000187:drug effects / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D008853:Microscopy; D059004:Topoisomerase I Inhibitors; D015003:Yeasts / Q000187:drug effects / Q000254:growth & development
chemical_list: D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D059004:Topoisomerase I Inhibitors