Ergot alkaloids contribute to virulence in an insect model of invasive aspergillosis.

Ergot alkaloids contribute to virulence in an insect model of invasive aspergillosis.
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麦角生物碱在侵袭性曲霉病的昆虫模型中有助于毒力。

DOI:
10.1038/s41598-017-09107-2
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发表时间:
2017-08-21
期刊:
影响因子:
4.6
通讯作者:
Arnold SL
Arnold SL
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Panaccione DG;Arnold SL

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烟曲霉(Aspergillus fumigatus)是侵袭性曲霉病的最常见原因,侵袭性曲霉病是一种常见的致命性肺部疾病,主要影响免疫功能低下的个体。这种机会性真菌病原体产生几类专门的代谢物,包括麦角生物碱途径的分支的产物,称为烟曲霉素。N.烟曲霉麦角生物碱及其与由来自植物栖息的棒曲霉科真菌中的交替途径分支产生的那些生物碱的关系已被充分表征,但这些生物碱在动物发病机理中的潜在作用尚未被广泛研究。研究了麦角生物碱对N.通过测量模式昆虫大蜡螟中的死亡率来测定烟曲霉的死亡率。将两种不同的野生型N. fumigata和三种不同的麦角生物碱突变体,这些突变体是通过先前的基因敲除获得的,并且麦角生物碱谱不同。消除所有麦角生物碱显著降低了N.烟曲霉G.大蜡螟(P < 0.0001)。积累中间产物但不积累途径最终产物烟麦角碱C的突变体的毒性也低于野生型(P < 0.0003)。数据表明,麦角生物碱有助于N.烟曲霉素C对全毒力有重要作用。
Neosartorya fumigata (Aspergillus fumigatus) is the most common cause of invasive aspergillosis, a frequently fatal lung disease primarily affecting immunocompromised individuals. This opportunistic fungal pathogen produces several classes of specialised metabolites including products of a branch of the ergot alkaloid pathway called fumigaclavines. The biosynthesis of the N. fumigata ergot alkaloids and their relation to those produced by alternate pathway branches in fungi from the plant-inhabiting Clavicipitaceae have been well-characterised, but the potential role of these alkaloids in animal pathogenesis has not been studied extensively. We investigated the contribution of ergot alkaloids to virulence of N. fumigata by measuring mortality in the model insect Galleria mellonella. Larvae were injected with conidia (asexual spores) of two different wild-type strains of N. fumigata and three different ergot alkaloid mutants derived by previous gene knockouts and differing in ergot alkaloid profiles. Elimination of all ergot alkaloids significantly reduced virulence of N. fumigata in G. mellonella (P < 0.0001). Mutants accumulating intermediates but not the pathway end product fumigaclavine C also were less virulent than the wild type (P < 0.0003). The data indicate that ergot alkaloids contribute to virulence of N. fumigata in this insect model and that fumigaclavine C is important for full virulence.
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