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The impact of episporic modification of Lichtheimia corymbifera on virulence and interaction with phagocytes
Computational and Structural Biotechnology Journal ( IF 6 ) Pub Date : 2021-01-20 , DOI: 10.1016/j.csbj.2021.01.023
Mohamed I. Abdelwahab Hassan , Monique Keller , Michael Hillger , Ulrike Binder , Stefanie Reuter , Kristina Herold , Anusha Telagathoti , Hans-Martin Dahse , Saiedeh Wicht , Nora Trinks , Sandor Nietzsche , Tanja Deckert-Gaudig , Volker Deckert , Ralf Mrowka , Ulrich Terpitz , Hans Peter Saluz , Kerstin Voigt

Fungal infections caused by the ancient lineage Mucorales are emerging and increasingly reported in humans. Comprehensive surveys on promising attributes from a multitude of possible virulence factors are limited and so far, focused on Mucor and Rhizopus. This study addresses a systematic approach to monitor phagocytosis after physical and enzymatic modification of the outer spore wall of Lichtheimia corymbifera, one of the major causative agents of mucormycosis. Episporic modifications were performed and their consequences on phagocytosis, intracellular survival and virulence by murine alveolar macrophages and in an invertebrate infection model were elucidated. While depletion of lipids did not affect the phagocytosis of both strains, delipidation led to attenuation of LCA strain but appears to be dispensable for infection with LCV strain in the settings used in this study. Combined glucano-proteolytic treatment was necessary to achieve a significant decrease of virulence of the LCV strain in Galleria mellonella during maintenance of the full potential for spore germination as shown by a novel automated germination assay. Proteolytic and glucanolytic treatments largely increased phagocytosis compared to alive resting and swollen spores. Whilst resting spores barely (1–2%) fuse to lysosomes after invagination in to phagosomes, spore trypsinization led to a 10-fold increase of phagolysosomal fusion as measured by intracellular acidification. This is the first report of a polyphasic measurement of the consequences of episporic modification of a mucormycotic pathogen in spore germination, spore surface ultrastructure, phagocytosis, stimulation of Toll-like receptors (TLRs), phagolysosomal fusion and intracellular acidification, apoptosis, generation of reactive oxygen species (ROS) and virulence.



中文翻译:

的episporic修改的影响Lichtheimia伞枝毒力,并与吞噬细胞的相互作用

由古代血统Mucorales引起的真菌感染正在出现,并且在人类中的报道越来越多。从众多可能的毒力因素对有希望的属性进行的综合调查是有限的,到目前为止,重点是MucorRhizopus。这项研究提出了一种系统的方法来监测物理和酶促修饰红顶荔枝外孢子壁后的吞噬作用,是毛霉菌病的主要病因之一。进行了孢子囊修饰,并阐明了它们对鼠肺泡巨噬细胞和无脊椎动物感染模型对吞噬作用,细胞内存活和毒力的影响。尽管脂质的消耗并没有影响两个菌株的吞噬作用,但在本研究中使用的脂质去除导致了LCA菌株的减弱,但似乎对于LCV菌株的感染是必不可少的。合并的葡聚糖蛋白水解处理是必要的,以实现应变LCV的毒力在显著降低蜡螟如新型自动萌发测定所示,在维持孢子萌发的全部潜力的过程中。与存活的静止和孢子肿胀相比,蛋白水解和糖酵解治疗可大大增加吞噬作用。静息孢子侵入吞噬体后几乎不融合(1-2%)与溶酶体融合,但用胞内酸化法测定,孢子胰蛋白酶消化使吞噬体融合融合度增加了10倍。这是多相测量粘膜真菌病原体在孢子萌发,孢子表面超微结构,吞噬作用,刺激Toll样受体(TLRs),吞噬体融合和胞内酸化,细胞凋亡,反应性产生的后果的多相测量的首次报道氧(ROS)和毒力。

更新日期:2021-02-01
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