白蛋白协调天然宿主防御机制对抗毛霉病，这一成果由克里特大学Georgios Chamilos小组经过不懈努力而取得。2026年1月7日出版的《自然》杂志发表了这一最新研究成果。

在这里，研究团队揭示了白蛋白通过调节真菌致病性在宿主防御Mucorales中的主要调节作用。他们的初步研究发现，在三个不同的毛霉病患者队列中，严重低白血症是一种突出的代谢异常和毛霉病预后不良的独立生物标志物。值得注意的是，纯化的白蛋白选择性地抑制毛霉菌在一系列病原体中的生长，白蛋白缺乏的小鼠对毛霉菌病表现出特异性的易感性。白蛋白的抗真菌活性是由结合的游离脂肪酸（FFAs）的释放介导的。白蛋白阻止FFA氧化，否则会消除其抗真菌特性，毛霉病患者的血清显示出高水平的氧化FFAs。生理上，白蛋白结合的FFAs通过抑制蛋白质合成来抑制关键毒力因子的表达，从而使毛霉菌在体内无毒。总之，该课题组人员确定了一种宿主防御机制，该机制指导病原体抑制其致病性程序，以响应由白蛋白调节的不利代谢信号。这些发现对毛霉病的发病机制和治疗具有重要意义。

据悉，毛霉病是由毛霉菌引起的一种新兴的、危及生命的人类感染。代谢性疾病通过尚不清楚的机制使越来越多的患者易患毛霉病，这表明未表征的宿主代谢效应物可能赋予对这种感染的保护性免疫。

附：英文原文

Title: Albumin orchestrates a natural host defence mechanism against mucormycosis

Author: Pikoulas, Antonis, Morianos, Ioannis, Nidris, Vassilis, Hamdy, Rania, Intze, Evangelia, Lpez-Lpez, ngeles, Moran-Garrido, Maria, Muthu, Valliappan, Halabalaki, Maria, Papaioanou, Varvara, Papadovasilaki, Maria, Kyrmizi, Irene, Gu, Yiyou, Camunas-Alberca, Sandra, Aerts, Robina, Mercier, Toine, Vanbiervliet, Yuri, Cho, Sung-Yeon, Spallone, Amy, Jiang, Ying, Samonakis, Dimitrios, Kastritis, Efstathios, Lax, Carlos, Tzardi, Maria, Eliopoulos, Aristides, Georgila, Konstantina, Carvalho, Agostinho, Kurzai, Oliver, Rudramurthy, Shivaprakash Mandya, Elie, Caroline, Lanternier, Fanny, Petratos, Kyriakos, Garre, Victoriano, Drakos, Elias, Maertens, Johan, Bruno, Vincent M., Kontoyiannis, Dimitrios P., Barbas, Coral, Soliman, Sameh S. M., Ibrahim, Ashraf S., Chamilos, Georgios

Issue&Volume: 2026-01-07

Abstract: Mucormycosis is an emerging, life-threatening human infection caused by Mucorales fungi1,2,3. Metabolic disorders uniquely predispose an ever-expanding group of patients to mucormycosis through poorly understood mechanisms1,2,4,5, suggesting that uncharacterized host metabolic effectors may confer protective immunity against this infection. Here we uncover a master regulatory role of albumin in host defence against Mucorales through the modulation of fungal pathogenicity. Our initial studies identified severe hypoalb uminaemia as a prominent metabolic abnormality and an independent biomarker of poor mucormycosis outcome across three distinct cohorts of patients with mucormycosis. Notably, purified albumin selectively inhibits Mucorales growth among a range of pathogens, and albumin-deficient mice display susceptibility specifically to mucormycosis. The antifungal activity of albumin is mediated by the release of bound free fatty acids (FFAs). Albumin prevents FFA oxidation, which otherwise abolishes their antifungal properties, and sera from patients with mucormycosis display high levels of oxidized FFAs. Physiologically, albumin-bound FFAs suppress the expression of key virulence factors by inhibiting protein synthesis, the reby rendering Mucorales avirulent in vivo. Overall, we identify a host defence mechanism that directs the pathogen to suppress its pathogenicity program in response to unfavourable metabolic cues regulated by albumin. These findings have major implications for the pathogenesis and management of mucormycosis.

DOI: 10.1038/s41586-025-09882-3

Source: https://www.nature.com/articles/s41586-025-09882-3