Candida albicans 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 of C. albicans can 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 of C. albicans
DIBI, but not
deferoxamine or
deferiprone, inhibited the growth of C. albicans at relatively low concentrations in vitro, 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 experimental C. albicans
vaginitis 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.