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宿主铁同化:毛霉病的发病机制与新疗法

Host-iron assimilation: pathogenesis and novel therapies of mucormycosis.

作者信息

Ibrahim Ashraf S

机构信息

The Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles (UCLA) Medical Center and the St. John's Cardiovascular Research Center, Torrance, CA, USA; David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

出版信息

Mycoses. 2014 Dec;57 Suppl 3(0 3):13-7. doi: 10.1111/myc.12232. Epub 2014 Sep 1.

Abstract

Mucormycosis is a fungal infection caused by organisms belonging to the order Mucorales. Although considered uncommon, mucormycosis has been steadily increasing in incidents for the last two decades. Mortality of the disease is unacceptably high despite antifungal therapy and surgical interventions. The lack of understanding of the pathogenesis of the disease and the absence of rapid diagnostic assay contribute to the poor prognosis of mucormycosis. The hyper susceptibility of patients with elevated available serum iron points to the critical role of the ability of Mucorales to acquire host iron as a critical virulence factor. Specifically patients with deferoxamine-therapy, hyperglycaemic with or without ketoacidosis, or other forms of acidosis are uniquely predisposed to mucormycosis. In this review, we discuss the molecular mechanisms of infection in these patient categories in an attempt to identify novel therapies for a disease with poor prognosis. Emphasis on the effect of glucose and free iron on host-pathogen interactions are also covered.

摘要

毛霉病是一种由毛霉目真菌引起的真菌感染。尽管被认为不常见,但在过去二十年中,毛霉病的发病率一直在稳步上升。尽管进行了抗真菌治疗和手术干预,该疾病的死亡率仍然高得令人无法接受。对该疾病发病机制的了解不足以及缺乏快速诊断检测方法导致毛霉病的预后较差。血清铁水平升高的患者的高易感性表明毛霉目获取宿主铁的能力作为关键毒力因子的关键作用。具体而言,接受去铁胺治疗、患有高血糖症(无论有无酮症酸中毒)或其他形式酸中毒的患者特别容易感染毛霉病。在这篇综述中,我们讨论了这些患者群体中感染的分子机制,试图为这种预后不良的疾病确定新的治疗方法。还涵盖了对葡萄糖和游离铁对宿主 - 病原体相互作用影响的强调。

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