IADR Abstract Archives
Effect of Iron on Oral Clinical Isolates of Candida Albicans
Objectives: Oral yeast C. albicans CAI4-strain exhibits iron-induced changes to cell-wall architecture in vitro, impacting its susceptibility to cell-wall perturbing (CWP) agents and macrophage-mediated phagocytosis. Whether such effects are seen in C. albicans grown in vivo in a low/high iron host is not known. Also, such iron-effects in wildtype (WT) SC5314-strain of C. albicans and oral clinical isolates are unknown.
Methods: Murine model of oropharyngeal candidiasis (OPC) was used for in vivo studies; mice were either iron depleted or repleted. C. albicans cells grown in low/high iron medium in vitro were used for: cell-wall component quantification (fluorescence microscopy), CWP-agent sensitivity assays (plate-spotting or liquid growth), minimal inhibitory concentration (MIC) assays against clinical antifungals, and phagocytosis by murine macrophages.
Results: High iron caused a more severe infection during OPC that led to a higher fungal load in the downstream gut. In vivo-grown fungal cells from low/high iron OPC mice showed lower/higher resistance to CWP-agents in vitro, respectively. Effect of iron on individual cell-wall components was not uniform among the tested oral clinical isolates of C. albicans, while WT SC5314-strain showed the same iron-effects as CAI4-strain. Incidence of high iron-induced increase in resistance to CWP-agents among the tested oral isolates and WT SC5314-strain was largely similar to CAI4-strain. MIC assays showed that high iron also increased the antifungal MIC of the oral isolates towards a majority of the commonly used clinical antifungals. Further, oral isolates showed enhanced exposure of cell-wall β-1,3-glucan under high iron that can potentially induce enhanced phagocytosis by macrophages.
Conclusions: Thus, oral isolates of C. albicans behave like CAI4 and WT SC5314 strains in exhibiting higher drug resistance and higher susceptibility to phagocytosis by macrophages when gown in high iron conditions.
Methods: Murine model of oropharyngeal candidiasis (OPC) was used for in vivo studies; mice were either iron depleted or repleted. C. albicans cells grown in low/high iron medium in vitro were used for: cell-wall component quantification (fluorescence microscopy), CWP-agent sensitivity assays (plate-spotting or liquid growth), minimal inhibitory concentration (MIC) assays against clinical antifungals, and phagocytosis by murine macrophages.
Results: High iron caused a more severe infection during OPC that led to a higher fungal load in the downstream gut. In vivo-grown fungal cells from low/high iron OPC mice showed lower/higher resistance to CWP-agents in vitro, respectively. Effect of iron on individual cell-wall components was not uniform among the tested oral clinical isolates of C. albicans, while WT SC5314-strain showed the same iron-effects as CAI4-strain. Incidence of high iron-induced increase in resistance to CWP-agents among the tested oral isolates and WT SC5314-strain was largely similar to CAI4-strain. MIC assays showed that high iron also increased the antifungal MIC of the oral isolates towards a majority of the commonly used clinical antifungals. Further, oral isolates showed enhanced exposure of cell-wall β-1,3-glucan under high iron that can potentially induce enhanced phagocytosis by macrophages.
Conclusions: Thus, oral isolates of C. albicans behave like CAI4 and WT SC5314 strains in exhibiting higher drug resistance and higher susceptibility to phagocytosis by macrophages when gown in high iron conditions.