Host Iron Withholding Demands Siderophore Utilization for Candida glabrata to Survive Macrophage Killing
A Schematic flowchart for infection of primary mouse macrophages with C. glabrata. Primary macrophages were differentiated from bone marrow cells harvested from control and flatiron mice, infected with the wild type, sit1Δ and reconstituted sit1Δ::SIT1 C. glabrata strains and CFU quantitated. Fe was added to the macrophage culture medium to stimulate FPN expression and cells were washed 3 times prior to infection with yeast strains. Data were analyzed with use of one-way ANOVA. B Infection of control primary bone marrow macrophages with C. glabrata showed robust Sit1-dependent survival with ferrichrome supplementation when compared to wild type C. glabrata grown exclusively under Fe deficiency (dashed line set at 100). This siderophore-dependent enhanced survival was absent in C. glabrata cells phagocytosed by primary macrophages derived from the flatiron mouse. Each experiment included 6 replicates per experimental sample. Results are shown as mean survival compared to the wild type grown in the absence of ferrichrome supplementation and are representative of at least 3 experiments. Bars represent the standard error.