Iron Restriction to Clinical Isolates of Candida albicans by the Novel Chelator DIBI Inhibits Growth and Increases Sensitivity to Azolesandin a Murine Model of Experimental Vaginitis.

Abstract

is an important opportunistic pathogen causing various human infections that are often treated with azole antifungals. The U.S. CDC now regards developing candidal antifungal resistance as a threat, creating a need for new and more effective antifungal treatments. Iron is an essential nutrient for all living cells, and there is growing evidence that interference with iron homeostasis ofcan improve its response to antifungals. This study was aimed at establishing whether withholding iron by currently used medical iron chelators and the novel chelator DIBI could restrict growth and also enhance the activity of azoles against clinical isolates ofDIBI, but not deferoxamine or deferiprone, inhibited the growth ofat relatively low concentrations, and this inhibition was reversed by iron addition. DIBI in combination with various azoles demonstrated stronger growth inhibition than the azoles alone and greatly prolonged the inhibition of cell multiplication. In addition, the administration of DIBI along with fluconazole (FLC) to mice inoculated with an FLC-sensitive isolate in a model of experimentalvaginitis showed a markedly improved clearance of infection. These results suggest that iron chelation by DIBI has the potential to enhance azole efficacy for the treatment of candidiasis.