IRON UPTAKE AND MUCOMYCOSIS PATHOGENESIS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Mucormycosis is a life-threatening infection that occurs in patients whose immune systems are not working properly. Unfortunately, these patients are increasingly common, and therefore the frequency of mucormycosis is rising. Despite aggressive treatment, which includes disfiguring surgery, more than 50% of patients with mucormycosis die. Clearly new strategies to prevent and treat mucormycosis are urgently needed. The most common cause of mucormycosis is the fungus, Rhizopus oryzae. Patients with too much iron in the blood have a higher risk of infection caused by this organism. We have found that R. Oryzae damage to human cells in the test tube is dependent on iron. Additionally, we have cloned a gene from the fungus that allows it to grab and ingest iron even in iron-rare conditions. Our current research plan is to better understand how iron impacts the ability of the fungus to injure human cells. We also plan to create a mutant of the fungus that cannot take up iron to confirm that this mutant causes less damage to human cells. This will prove the role of iron in allowing the fungus to cause infection. To perform these experiments, it is necessary to grow in the test tube the same type of human cells that the fungus normally attacks. A classic feature of mucormycosis infections is the tendency of the fungus to invade blood vessels, where iron-rich blood is found.