Deletion of the α-(1,3)-glucan synthase genes induces a restructuring of the conidial cell wall responsible for the avirulence of Aspergillus fumigatus.
Deletion of the α-(1,3)-glucan synthase genes induces a restructuring of the conidial cell wall responsible for the avirulence of Aspergillus fumigatus.
复制标题
DOI：
10.1371/journal.ppat.1003716
复制
发表时间：
2013
期刊：
影响因子：
6.7
通讯作者：
Latgé JP
中科院分区：
文献类型：
--
作者：
Beauvais A;Bozza S;Kniemeyer O;Formosa C;Balloy V;Henry C;Roberson RW;Dague E;Chignard M;Brakhage AA;Romani L;Latgé JP
α-(1,3)-葡聚糖是烟曲霉细胞壁的主要成分，是一种机会性人类真菌病原体。该真菌有3个基因（AGS1、AGS2和AGS3）控制α-(1,3)-葡聚糖的生物合成。三个AGS基因的缺失导致其细胞壁缺乏α-(1,3)-葡聚糖的三重突变体；但其体外生长和萌发与亲本菌株完全相同。在实验小鼠曲霉病模型中，该突变株的致病性低于亲本菌株。AGS的缺失导致分生孢子细胞壁发生了广泛的结构改变，特别是分生孢子表面的小棒层被无定形糖蛋白基质覆盖。这种表面修饰是体内分生孢子活力降低的原因，这解释了三重agsΔ突变体毒力下降的原因。烟曲霉是人类主要的霉菌病原体，在免疫力低下的患者中造成危及生命的全身感染。由于其外部定位和特异性组成，真菌细胞壁是宿主免疫细胞识别和相互作用的目标。在烟曲霉中，α-(1,3)-葡聚糖是细胞外基质的关键成分，细胞外基质包裹着细胞壁β-(1,3)-葡聚糖-几丁质纤维核心。有趣的是，缺失负责α-(1,3)-葡聚糖合成的基因导致突变体在体外表现出野生型表型；而细胞壁组织的改变导致这种真菌在体内是无毒的。这项研究证实，细胞壁成分的任何修饰都与真菌产生的代偿反应有关，这些反应是为了抵消细胞壁上的压力，当受到宿主免疫系统的攻击时，这种压力可能导致意想不到的真菌反应。
α-(1,3)-Glucan is a major component of the cell wall of Aspergillus fumigatus, an opportunistic human fungal pathogen. There are three genes (AGS1, AGS2 and AGS3) controlling the biosynthesis of α-(1,3)-glucan in this fungal species. Deletion of all the three AGS genes resulted in a triple mutant that was devoid of α-(1,3)-glucan in its cell wall; however, its growth and germination was identical to that of the parental strain in vitro. In the experimental murine aspergillosis model, this mutant was less pathogenic than the parental strain. The AGS deletion resulted in an extensive structural modification of the conidial cell wall, especially conidial surface where the rodlet layer was covered by an amorphous glycoprotein matrix. This surface modification was responsible for viability reduction of conidia in vivo, which explains decrease in the virulence of triple agsΔ mutant. Aspergillus fumigatus is the predominant mold pathogen of humans, responsible for life-threatening systemic infections in patients with depressed immunity. Because of its external localization and specific composition, the fungal cell wall represents a target for recognition by and interaction with the host immune cells. In A. fumigatus, α-(1,3)-glucan is a key component of the extracellular matrix, which encloses the cell wall β-(1,3)-glucan-chitin fibrillar core. Interestingly, the deletion of the genes responsible for α-(1,3)-glucan synthesis resulted in a mutant that exhibited wild type phenotype in vitro; while the altered cell wall organization resulted in this fungus being avirulent in vivo. This study confirms that any modification in the cell wall components is associated with compensatory reactions developed by the fungus to counteract stress on the cell wall that may result in unexpected fungal response when challenged with the host immune system.
登录
查看更多内容
影响因子：
3.5
作者：
Dague, E.;Jauvert, E.;Ressier, L.
通讯作者：
Ressier, L.
影响因子：
4.4
作者：
Bozza, Silvia;Clavaud, Cecile;Romani, Luigina
通讯作者：
Romani, Luigina
影响因子：
4.9
作者：
Jimenez-Ortigosa, Cristina;Aimanianda, Vishukumar;Latge, Jean-Paul
通讯作者：
Latge, Jean-Paul
影响因子：
6.9
作者：
BRIAN, PW;NORRIS, GLF;LOWE, D
通讯作者：
LOWE, D
影响因子：
2.9
作者：
Candiano, G;Bruschi, M;Righetti, PG
通讯作者：
Righetti, PG