Laboratório de Bioquímica e Imunologia das Micoses, Departamento de Microbiologia e Parasitologia, Instituto Biomédico, Universidade Federal Fluminense, Niterói, Brazil.
Pós-Graduação em Doenças Infecciosas e Parasitárias, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Front Cell Infect Microbiol. 2021 Jan 8;10:565571. doi: 10.3389/fcimb.2020.565571. eCollection 2020.
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 (), 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 , and 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 incorporates, surface/secreted GXM of and the surface accumulation of the polysaccharide enhances virulence and . In this work, we characterized the ability of to produce cellular-attached (C-gly-) and secreted (E-gly) glycans with reactivity to GXM mAbs. These C-gly- are readily incorporated on the surface of acapsular cap59; however, in contrast to GXM, C-gly- had no xylose and glucuronic acid in its composition. Mapping of recognized GXM synthesis/export proteins confirmed the presence of orthologs in the database. Evaluation of C-gly and E-gly of from strains of distinct monophyletic clades showed serological reactivity to GXM mAbs, despite slight differences in their molecular dimensions. These C-gly- and E-gly- also reacted with sera of cryptococcosis patients. In turn, sera from histoplasmosis patients recognized glycans, suggesting immunogenicity and the presence of cross-reacting antibodies. Additionally, C-gly- and E-gly- coated cap59 were more resistant to phagocytosis and macrophage killing. C-gly- and E-gly- coated cap59 were also able to kill larvae of . These GXM-like 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.
细胞壁是真菌王国中普遍存在的结构，其某些特征因物种而异。还可以存在其他外部结构，例如（）的胶囊，它是主要的毒力因子，主要由葡聚糖醛酸甘露聚糖（GXM）组成，具有抗吞噬和抗炎作用。文献表明，其他隐球菌物种甚至更进化的远缘物种，如，和，可以产生类似 GXM 的多糖，这些多糖与 GXM 特异性单克隆抗体（mAb）具有血清学反应性，并且这些复杂多糖与隐球菌 GXM 具有相似的组成和抗吞噬特性。此前，我们证明了真菌（）可以摄取、表面/分泌（）的 GXM，并且多糖的表面积累增强了的毒力和。在这项工作中，我们描述了产生对 GXM mAb 具有反应性的细胞附着（C-糖基化）和分泌（E-糖基化）聚糖的能力。这些 C-糖基化很容易整合到无囊（）的表面；然而，与 GXM 不同的是，C-糖基化在其组成中没有木糖和葡萄糖醛酸。对识别 GXM 合成/输出蛋白的映射证实了在数据库中存在同源物。来自不同单系进化枝的菌株的 C-糖基化和 E-糖基化的评估显示，它们对 GXM mAb 具有血清学反应性，尽管它们的分子尺寸略有不同。这些 C-糖基化和 E-糖基化也与隐球菌病患者的血清发生反应。反过来，组织胞浆菌病患者的血清识别了真菌聚糖，表明存在免疫原性和交叉反应性抗体。此外，C-糖基化和 E-糖基化包被的（）cap59 更能抵抗吞噬和巨噬细胞杀伤。C-糖基化和 E-糖基化包被的（）cap59 也能够杀死幼虫。这些类似 GXM 的真菌聚糖，以及其他致病性真菌产生的聚糖，在宿主-病原体相互作用中也可能很重要，与它们的调节相关的因素可能是组织胞浆菌病管理的重要目标。
