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烟曲霉素会导致宿主细胞损伤。

Fumagillin Contributes to Host Cell Damage.

作者信息

Guruceaga Xabier, Perez-Cuesta Uxue, Pellon Aize, Cendon-Sanchez Saioa, Pelegri-Martinez Eduardo, Gonzalez Oskar, Hernando Fernando Luis, Mayayo Emilio, Anguita Juan, Alonso Rosa M, Keller Nancy P, Ramirez-Garcia Andoni, Rementeria Aitor

机构信息

Fungal and Bacterial Biomics Research Group, Department of Immunology, Microbiology and Parasitology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain.

Inflammation and Macrophage Plasticity Laboratory, CIC bioGUNE-BRTA (Basque Research and Technology Alliance), 48160 Derio, Spain.

出版信息

J Fungi (Basel). 2021 Nov 3;7(11):936. doi: 10.3390/jof7110936.

Abstract

The activity of fumagillin, a mycotoxin produced by , has not been studied in depth. In this study, we used a commercial fumagillin on cultures of two cell types (A549 pneumocytes and RAW 264.7 macrophages). This toxin joins its target, MetAP2 protein, inside cells and, as a result, significantly reduces the electron chain activity, the migration, and the proliferation ability on the A549 cells, or affects the viability and proliferation ability of the RAW 264.7 macrophages. However, the toxin stimulates the germination and double branch hypha production of fungal cultures, pointing out an intrinsic resistant mechanism to fumagillin of fungal strains. In this study, we also used a fumagillin non-producer strain (∆) as well as its complemented strain (∆ and we tested the fumagillin secretion of the fungal strains using an Ultra High-Performance Liquid Chromatography (UHPLC) method. Furthermore, fumagillin seems to protect the fungus against phagocytosis in vitro, and during in vivo studies using infection of immunosuppressed mice, a lower fungal burden in the lungs of mice infected with the ∆ mutant was demonstrated.

摘要

烟曲霉产生的霉菌毒素烟曲霉素的活性尚未得到深入研究。在本研究中,我们将一种市售烟曲霉素用于两种细胞类型(A549肺细胞和RAW 264.7巨噬细胞)的培养。这种毒素在细胞内与它的靶标甲硫氨酸氨肽酶2(MetAP2)蛋白结合,结果显著降低了A549细胞的电子链活性、迁移能力和增殖能力,或影响RAW 264.7巨噬细胞的活力和增殖能力。然而,该毒素刺激真菌培养物的萌发和双分支菌丝产生,指出了真菌菌株对烟曲霉素的一种内在抗性机制。在本研究中,我们还使用了一株不产生烟曲霉素的菌株(∆)及其互补菌株(∆),并使用超高效液相色谱(UHPLC)方法检测了真菌菌株的烟曲霉素分泌情况。此外,烟曲霉素似乎在体外保护真菌免受吞噬作用,并且在使用免疫抑制小鼠感染进行的体内研究中,证明感染∆突变体的小鼠肺部真菌负荷较低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/273c/8619997/2b1300f3a5cb/jof-07-00936-g001.jpg

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