当前位置: X-MOL 学术Front. Cell. Infect. Microbiol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Histoplasma capsulatum Glycans From Distinct Genotypes Share Structural and Serological Similarities to Cryptococcus neoformans Glucuronoxylomannan
Frontiers in Cellular and Infection Microbiology ( IF 5.7 ) Pub Date : 2020-11-17 , DOI: 10.3389/fcimb.2020.565571
Diego de Souza Gonçalves 1, 2 , Claudia Rodriguez de La Noval 1, 3 , Marina da Silva Ferreira 1, 4 , Leandro Honorato 3 , Glauber Ribeiro de Sousa Araújo 5 , Susana Frases 5 , Claudia Vera Pizzini 6 , Joshua D Nosanchuk 7 , Radames J B Cordero 8 , Marcio L Rodrigues 3, 9 , José Mauro Peralta 4 , Leonardo Nimrichter 3 , Allan J Guimarães 1
Affiliation  

The cell wall is a ubiquitous structure in the fungal kingdom, with some features varying depending on the species. Additional external structures can be present, such as the capsule of Cryptococcus neoformans (Cn), its major virulence factor, mainly composed of glucuronoxylomannan (GXM), with anti-phagocytic and anti-inflammatory properties. The literature shows that other cryptococcal species and even more evolutionarily distant species, such as the Trichosporon asahii, T. mucoides, and Paracoccidioides brasiliensis can produce GXM-like polysaccharides displaying serological reactivity to GXM-specific monoclonal antibodies (mAbs), and these complex polysaccharides have similar composition and anti-phagocytic properties to cryptococcal GXM. Previously, we demonstrated that the fungus Histoplasma capsulatum (Hc) incorporates, surface/secreted GXM of Cn and the surface accumulation of the polysaccharide enhances Hc virulence in vitro and in vivo. In this work, we characterized the ability of Hc to produce cellular-attached (C-gly-Hc) and secreted (E-gly) glycans with reactivity to GXM mAbs. These C-gly-Hc are readily incorporated on the surface of acapsular Cn cap59; however, in contrast to Cn GXM, C-gly-Hc had no xylose and glucuronic acid in its composition. Mapping of recognized Cn GXM synthesis/export proteins confirmed the presence of orthologs in the Hc database. Evaluation of C-gly and E-gly of Hc from strains of distinct monophyletic clades showed serological reactivity to GXM mAbs, despite slight differences in their molecular dimensions. These C-gly-Hc and E-gly-Hc also reacted with sera of cryptococcosis patients. In turn, sera from histoplasmosis patients recognized Cn glycans, suggesting immunogenicity and the presence of cross-reacting antibodies. Additionally, C-gly-Hc and E-gly-Hc coated Cn cap59 were more resistant to phagocytosis and macrophage killing. C-gly-Hc and E-gly-Hc coated Cn cap59 were also able to kill larvae of Galleria mellonella. These GXM-like Hc glycans, as well as those produced by other pathogenic fungi, may also be important during host-pathogen interactions, and factors associated with their regulation are potentially important targets for the management of histoplasmosis.



中文翻译:

不同基因型的组织胞浆菌聚糖与新型隐球菌葡糖醛酸木甘聚糖具有结构和血清学相似性

细胞壁是真菌界中普遍存在的结构,其某些特征因物种而异。可以存在额外的外部结构,例如胶囊新型隐球菌中文),其主要毒力因子主要由葡萄糖醛酸木甘露聚糖(GXM)组成,具有抗吞噬和抗炎特性。文献表明,其他隐球菌物种甚至进化上更遥远的物种,例如旭毛孢子菌、粘液毛孢子菌, 和巴西副球孢子菌可以产生对 GXM 特异性单克隆抗体 (mAb) 表现出血清学反应性的 GXM 样多糖,并且这些复合多糖具有与隐球菌 GXM 相似的组成和抗吞噬特性。之前我们已经证明了真菌荚膜组织胞浆菌 (Hc)包含表面/分泌的 GXM中文并且多糖的表面积累增强HC毒力体外体内。在这项工作中,我们描述了以下能力:HC产生细胞附着的(C-gly-HC) 和与 GXM mAb 具有反应性的分泌型 (E-gly) 聚糖。这些C-甘氨酸-HC很容易结合在胶囊的表面中文帽59;然而,与中文GXM,C-甘氨酸-HC其成分中不含木糖和葡萄糖醛酸。已识别的映射中文GXM 合成/输出蛋白证实了直向同源物的存在HC数据库。C-gly 和 E-gly 的评价HC来自不同单系分支菌株的 GXM 单克隆抗体表现出血清学反应性,尽管它们的分子尺寸略有差异。这些C-甘氨酸-HC和E-甘氨酸-HC也与隐球菌病患者的血清发生反应。反过来,来自组织胞浆菌病患者的血清被识别中文聚糖,表明免疫原性和交叉反应抗体的存在。此外,C-甘氨酸-HC和E-甘氨酸-HC涂层中文cap59对吞噬作用和巨噬细胞杀伤具有更强的抵抗力。C-甘氨酸-HC和E-甘氨酸-HC涂层中文cap59 还能够杀死大蜡螟。这些类似 GXM 的HC聚糖以及其他病原真菌产生的聚糖在宿主与病原体相互作用过程中也可能很重要,与其调节相关的因素是组织胞浆菌病管理的潜在重要目标。

更新日期:2021-01-08
down
wechat
bug