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Abstract

Human serum, transferrin, and apotransferrin are known to profoundly inhibit the growth of Candida albicans by iron deprivation. On the other hand, iron overload (iron saturated transferrin) is a serious risk factor for candidiasis in newborn and in leukemic patients. We tested the efficacy of fluconazole and the previously demonstrated synergy of fluconazole and effector cells against C. albicans under iron overload conditions where efficacy might be diminished. We confirm that exogenous iron completely reversed the inhibitory effect of human serum and report that the efficacy of fluconazole against C. albicans was not significantly compromised in a 24 h assay system. Although exogenous iron inhibited fungistatic activity of monocyte-derived macrophages, it did not interfere with the synergistic candidacidal activity of fluconazole and monocyte-derived macrophages. In 72 h assays, where fluconazole had candidacidal activity, exogenous iron did not compromise efficacy of fluconazole, and fluconazole activity was often increased. These in vitro results suggest that effectiveness of fluconazole therapy would not be compromised in iron overload situations in vivo.

The Synergism of the Small Molecule ENOblock and Fluconazole Against Fluconazole-Resistant Candida albicans

“…ENOblock alone or in combination with FLC showed significant inhibitory activity against biofilm formation of C. albicans SC5314 (Supplementary Figure S3), and the combination of ENOblock and FLC also showed in vivo activity against C. albicans SC5314 although in vitro synergy measured by antifungal susceptibility test was not observed (Supplementary Figure S4). According to previous reports (Minn et al, 1997; Zhanel et al, 2001), it is known that in vitro testing of some compounds can be used to predict in vivo efficacy, but also may not correlate with in vivo efficacy, due to the influence of serum, formulation of compounds, and some other factors. It is possible to observe the in vivo synergism against C. albicans SC5314 in the animal study.…”

Complex Interaction of Deferasirox and Pythium insidiosum: Iron-Dependent Attenuation of Growth In Vitro and Immunotherapy-Like Enhancement of Immune Responses In Vivo

“…insidiosum in vitro . In line with this, the addition of exogenous iron to growth medium has been reported to not enhance fungal growth, probably because trace levels of iron in RPMI medium allow fungi to grow very well [16]. The use of fluorescent dyes such as the safranine and the acriflavin would add additional knowledge in iron-specific changes in cell wall and organelle of P .…”

“…Iron overload is known to exacerbate fungal infections such as aspergillosis, candidiasis and especially mucormycosis by enhancing aggressive proliferation of microbes in host tissue [11, 16, 18]. The elevated iron availability also impairs host immune responses, as observed in patients with thalassemia or hemochromatosis, which frequently have reduced CD8+ T-cell counts that respond positively to iron chelation therapy [7].…”

Resurgence and Repurposing of Antifungal Azoles by Transition Metal Coordination for Drug Discovery

“…In some cases, metal ions can regulate the activity of an organic drug or vice versa without requiring the intake of the corresponding metallodrug. Such examples concerning AAs are manifold in the literature [35][36][37][38][39][40][41][42][43][44][45][46][47].…”