Padró-Villegas Leonardo, Gómez-Gaviria Manuela, Martínez-Duncker Iván, López-Ramírez Luz A, Martínez-Álvarez José A, Niño-Vega Gustavo A, Mora-Montes Héctor M
Departamento de Biología, División de Ciencias Naturales y Exactas, Campus Guanajuato, Universidad de Guanajuato, Noria Alta s/n, col. Noria Alta, C.P. 36050 Guanajuato, Gto, Mexico.
Laboratorio de Glicobiología Humana y Diagnóstico Molecular, Centro de Investigación en Dinámica Celular, Instituto de Investigación en Ciencias Básicas y Aplicadas, Universidad Autónoma del Estado de Morelos, Cuernavaca, Mor. 62209, Mexico.
Cell Surf. 2025 Jan 6;13:100139. doi: 10.1016/j.tcsw.2024.100139. eCollection 2025 Jun.
is one of the leading etiological agents of sporotrichosis, a cutaneous and subcutaneous mycosis worldwide distributed. This organism has been recently associated with epidemic outbreaks in Brazil. Despite the medical relevance of this species, little is known about its virulence factors, and most of the information on this subject is extrapolated from . Here, we generated mutants, where was silenced. In , this gene encodes a glycoprotein with adhesive properties required for virulence. The silencing led to an abnormal cellular phenotype, with smaller, round yeast-like cells that aggregate. Cell aggregation was disrupted with glucanase, suggesting this phenotype is linked to changes in the cell wall. The cell wall characterization confirmed changes in the structural polysaccharide β-1,3-glucan, which increased in quantity and exposure at the cell surface. This was accompanied by a reduction in protein content and -linked glycans. Mutant strains with high -silencing levels showed minimal levels of 3-carboxy-cis,cis-muconate cyclase activity, this glycoprotein's predicted enzyme function, and decreased ability to bind laminin and fibronectin. These phenotypical changes coincided with abnormal interaction with human peripheral blood mononuclear cells, where production of IL-1β, IL-17, and IL-22 was reduced and the strong dependence on cytokine stimulation mannose receptor was lost. Phagocytosis by monocyte-derived macrophages was increased and virulence attenuated in a larvae. In conclusion, Gp70 is an abundant cell wall glycoprotein in that contributes to virulence and proper interaction with innate immnune cells.
是孢子丝菌病的主要病原体之一，孢子丝菌病是一种在全球范围内分布的皮肤和皮下真菌病。这种生物体最近与巴西的疫情爆发有关。尽管该物种具有医学相关性，但其毒力因子却鲜为人知，关于这一主题的大多数信息都是从……推断而来。在这里，我们构建了突变体，其中……被沉默。在……中，该基因编码一种具有毒力所需粘附特性的糖蛋白。……的沉默导致细胞表型异常，形成更小的圆形酵母样细胞并聚集。用葡聚糖酶可破坏细胞聚集，表明这种表型与细胞壁变化有关。细胞壁特征分析证实了结构多糖β-1,3-葡聚糖的变化，其数量增加且在细胞表面的暴露增多。同时蛋白质含量和……连接聚糖减少。高……沉默水平的突变株显示出最低水平的3-羧基-顺,顺-粘康酸环化酶活性，这是该糖蛋白的预测酶功能，并且与层粘连蛋白和纤连蛋白结合的能力下降。这些表型变化与与人外周血单核细胞的异常相互作用同时出现，其中IL-1β、IL-17和IL-22的产生减少，并且对细胞因子刺激甘露糖受体的强烈依赖性丧失。单核细胞衍生的巨噬细胞的吞噬作用增强，并且在……幼虫中毒力减弱。总之，Gp70是……中一种丰富的细胞壁糖蛋白，它有助于毒力以及与先天免疫细胞的正常相互作用。
