2.3.2. Iron Toxicity

Iron is involved in many biological processes, but can be toxic in excess. Studies have shown its toxicity in *S. cerevisiae* and fungal pathogens, but they have also demonstrated that targeting and interfering in iron acquisition mechanisms can also be detrimental. Reports indicate that iron or iron compounds are fungistatic against *F. oxysporum* and its mycotoxins in a dose dependent manner [216,217]. In discussing iron toxicity, it is also important to note that the interference of homeostatic systems can result in the inhibition of iron acquisition, which can also be toxic. Leal et al. demonstrated this with the utilization of lactoferrin, an iron-binding glycoprotein, as a topical agent to obstruct iron uptake mechanisms of *A. fumigatus* and *F. oxysporum* in mice [92,93]. Results indicated that, during corneal fungal infection, these fungi acquired iron through siderophores and that the iron-binding agent blocked the ability of the pathogen to acquire siderophore-bound iron, highlighting the inability of the fungi to proliferate without access to iron [93]. In *S. cerevisiae*, iron toxicity is related to the ability of the cell to transport cytosolic iron to the vacuole via Ccc1 [91,248]. Lin et al. showed that *ccc1*∆ mutants could not transfer cytosolic iron to the vacuole under anaerobic conditions, even with the overexpression of iron mitochondrial transporter Mrs3, effectively inducing toxicity [248]. The ability to alter and control homeostatic mechanisms are determinants of the fungal ability to resist excessive iron concentrations.
