IRON UPTAKE AND MUCOMYCOSIS PATHOGENESIS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者的研究机构。 毛霉菌病是一种危及生命的感染，发生在免疫系统不能正常工作的患者身上。 不幸的是，这些患者越来越常见，因此毛霉菌病的频率正在上升。 尽管积极的治疗，包括毁容手术，超过50%的毛霉菌病患者死亡。 显然，迫切需要新的策略来预防和治疗毛霉菌病。 毛霉菌病最常见的原因是真菌，根霉。血液中含有过多铁的患者感染这种微生物的风险更高。我们发现R.水稻对试管中人体细胞的破坏依赖于铁。 此外，我们还从这种真菌中克隆了一种基因，使其即使在缺铁的条件下也能摄取铁。 我们目前的研究计划是更好地了解铁如何影响真菌损伤人体细胞的能力。 我们还计划创造一种不能吸收铁的真菌突变体，以证实这种突变体对人体细胞的损伤较小。 这将证明铁在允许真菌引起感染中的作用。 为了进行这些实验，有必要在试管中培养真菌通常攻击的相同类型的人类细胞。 毛霉菌病感染的一个典型特征是真菌倾向于侵入血管，在血管中发现富含铁的血液。

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.