IRON UPTAKE AND MUCOMYCOSIS PATHOGENESIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 毛霉病是一种危及生命的感染，发生在免疫系统无法正常工作的患者身上。不幸的是，这些患者越来越常见，因此毛霉病的发生率也在上升。尽管进行了积极的治疗，包括毁容手术，但超过50%的毛霉病患者死亡。显然，迫切需要新的策略来预防和治疗毛霉病。 毛霉病最常见的原因是真菌米根霉。血液中铁含量过高的患者感染这种微生物的风险更高。我们发现稻瘟病菌在试管中对人细胞的损伤依赖于铁。此外，我们还从真菌中克隆了一种基因，使其即使在铁稀少的情况下也能抓取和摄取铁。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类细胞的能力。我们还计划创造一种不能吸收铁的真菌突变株，以确认该突变株对人类细胞造成的损害较小。这将证明铁在允许真菌引起感染中所起的作用。 为了进行这些实验，有必要在试管中培养真菌通常攻击的同一类型的人类细胞。毛霉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。在这种入侵过程中，真菌必须抓住并穿透排列在血管壁上的细胞，称为内皮细胞。因此，有必要在试管中培养内皮细胞。最可用、最丰富的内皮细胞来源是脐带静脉。脐带被匿名从分娩后丢弃的胎盘上移除。在患者和脐带之间没有任何联系，这将使患者的身份被知道。鉴于脐带之间没有任何联系，脐带在分娩后被匿名从胎盘上移除，如果不用于这项研究，脐带将被破坏的事实，对患者的风险是最小的。考虑到有可能发现一种疫苗来预防常见的和危及生命的根霉感染，这项研究的潜在好处很高。因此，风险与收益之比是非常有利的。

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 ar enot 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. During this invasion, the fungus must grab hold of and penetrate through the cells that line the blood vesel wall, called endothelial cells. Therefore, it is necessary to grow endothelial cells in the test tube. The most available, richest source of endothelial cells are the umbilical cord veins. The umbilical cords are anonymously removed from placentas that are to be discarded after delivery. There is no link between the patient and the umbilical cord that would allow the patient's identity to be known. Given the absence of any link between the umbilical cord, the fact that the umbilical cords are anonymously removed from the placenta after delivery of the child, the fact that the umbilical cords would be destroyed if they were not used for this research, the risk to the patient is minimal. Given the potential for discoveries to be made that could lead to a vaccine to prevent common and life-threatening Rhizopus infections, the potential benefit of this research is high. Therefore, the risk:benefit ratio is highly favorable.