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首页> 外文期刊>mSphere >Biosynthesis of β-(1→5)-Galactofuranosyl Chains of Fungal-Type and O-Mannose-Type Galactomannans within the Invasive Pathogen Aspergillus fumigatus
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Biosynthesis of β-(1→5)-Galactofuranosyl Chains of Fungal-Type and O-Mannose-Type Galactomannans within the Invasive Pathogen Aspergillus fumigatus

机译:生物合成β-(1→5) - 侵袭性病原体Fumigatus内的真菌型和O-甘露糖型半乳癌罐的高乳粥乳糖基链

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The pathogenic fungus Aspergillus fumigatus contains galactomannans localized on the surface layer of its cell walls, which are involved in various biological processes. Galactomannans comprise α-(1→2)-/α-(1→6)-mannan and β-(1→5)-/β-(1→6)-galactofuranosyl chains. We previously revealed that GfsA is a β-galactofuranoside β-(1→5)-galactofuranosyltransferase involved in the biosynthesis of β-(1→5)-galactofuranosyl chains. In this study, we clarified the biosynthesis of β-(1→5)-galactofuranosyl chains in A. fumigatus . Two paralogs exist within A. fumigatus : GfsB and GfsC. We show that GfsB and GfsC, in addition to GfsA, are β-galactofuranoside β-(1→5)-galactofuranosyltransferases by biochemical and genetic analyses. GfsA, GfsB, and GfsC can synthesize β-(1→5)-galactofuranosyl oligomers at up to lengths of 7, 3, and 5 galactofuranoses within an established in vitro highly efficient assay of galactofuranosyltransferase activity. Structural analyses of galactomannans extracted from Δ gfsB , Δ gfsC , Δ gfsAC , and Δ gfsABC strains revealed that GfsA and GfsC synthesized all β-(1→5)-galactofuranosyl residues of fungal-type and O -mannose-type galactomannans and that GfsB exhibited limited function in A. fumigatus . The loss of β-(1→5)-galactofuranosyl residues decreased the hyphal growth rate and conidium formation ability and increased the abnormal hyphal branching structure and cell surface hydrophobicity, but this loss is dispensable for sensitivity to antifungal agents and virulence toward immunocompromised mice. IMPORTANCE β-(1→5)-Galactofuranosyl residues are widely distributed in the subphylum Pezizomycotina of the phylum Ascomycota. Pezizomycotina includes many plant and animal pathogens. Although the structure of β-(1→5)-galactofuranosyl residues of galactomannans in filamentous fungi was discovered long ago, it remains unclear which enzyme is responsible for biosynthesis of this glycan. Fungal cell wall formation processes are complicated, and information concerning glycosyltransferases is essential for understanding them. In this study, we showed that GfsA and GfsC are responsible for the biosynthesis of all β-(1→5)-galactofuranosyl residues of fungal-type and O -mannose-type galactomannans. The data presented here indicate that β-(1→5)-galactofuranosyl residues are involved in cell growth, conidiation, polarity, and cell surface hydrophobicity. Our new understanding of β-(1→5)-galactofuranosyl residue biosynthesis provides important novel insights into the formation of the complex cell wall structure and the virulence of the members of the subphylum Pezizomycotina.
机译:致病性真菌曲霉属Fumigatus含有本地化在其细胞壁的表面层上的半乳甘露聚糖,其参与各种生物方法。半乳甘露聚糖包含α-(1→2) - /α-(1→6) - 甲烷和β-(1→5) - /β-(1→6) - 甲酰氯浑蛋链。我们以前透露,GFSA是β-(1→5)-Galactofuranosyl转移酶,参与β-(1→5)-Galactofuranylyl链的生物合成。在这项研究中,我们阐明了A. fumigatus中的β-(1→5)-Galactofuranylyl链的生物合成。 A. fumigatus:GFSB和GFSC中存在两个副病虫病。除了GFSA之外,我们表明GFSB和GFSC是通过生化和遗传分析的β-半乳粥样蛋白酶β-(1→5)-Galactofuranylyl转移酶。 GFSA,GFSB和GFSC可以合成β-(1→5)-Galactofuranylyl寡聚体,其长度为7,3和5个半乳乳铀醛酸酯内的半乳糖基烷基转移酶活性的体外高效测定中。从δGFSB,δGFSC,δGFSAC和δGFSABC菌株中提取的半乳甘露聚糖的结构分析表明,GFSA和GFSC合成了真菌型和O-甲型型半乳甘露聚糖的所有β-(1→5)-Galactofuranylyl残留物,以及GFSB在A. fumigatus中展出了有限的功能。 β-(1→5) - 高亚乳粥蛋白糖基残留物的损失降低了亚酚醛生长速率和胞菌形成能力,并增加了异常的酸杂环分支结构和细胞表面疏水性,但这种损失可以分配对抗真菌剂的敏感性和致毒性朝向免疫功能性的小鼠的敏感性。重要性β-(1→5) - 高亚乳粥蛋白糖基残留物广泛分布在亚义核的亚毒素番茄植物中。 Pezizomycotina包括许多植物和动物病原体。尽管很久以前发现了丝状真菌中的半乳甘露聚糖的β-(1→5)的结构 - Galactomannans的乳粥蛋白糖基残留物,但仍不清楚哪种酶对该聚糖的生物合成负责。真菌细胞壁形成过程复杂,有关糖基转移酶的信息对于理解它们是必不可少的。在这项研究中,我们表明GFSA和GFSC负责真菌型和o-曼诺型半乳甘露聚糖的所有β-(1→5)-Galactofuranylyl残基的生物合成。本文呈现的数据表明β-(1→5) - 高亚乳粥基残基参与细胞生长,结合,极性和细胞表面疏水性。我们对β-(1→5) - 高乳粥醇糖基残留物生物合成的新了解为形成复杂的细胞壁结构和亚细菌植物构件的毒力提供了重要的新颖洞察。

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