Instituto Universitario Fernández-Vega, Universidad de Oviedo, Oviedo, Spain.
Departamento de Biología functional, Universidad de Oviedo, Oviedo, Spain.
Pol J Microbiol. 2022 Mar 14;71(1):55-62. doi: 10.33073/pjm-2022-008.
The most common causal agents of fungal keratitis are yeasts of the genus. Adhesion constitutes the first stage of pathogenesis. Previous studies have shown that glycosaminoglycans from the corneal cell surface play an essential role in bacterial keratitis, although little is known about their role in fungal infections. The objective of this work is to analyze the role that glycosaminoglycans (GAGs) play in the adhesion of fungi of the genus to corneal epithelial cells. The participation of GAGs in the adhesion of fungi was studied through the specific inhibition of the synthesis of these molecules by enzymatic digestion using specific lyases and the silencing of various genes involved in heparan sulfate sulfation. The results seem to indicate that glycosaminoglycans act to some extent as receptors for this fungus, although there are differences between fungal species. Treatment with inhibitors partially reduced the adherence of fungal species. Digestion of cell surface heparan sulfate further reduced the adherence of and compared to chondroitin sulfate, indicating that the binding is preferentially mediated by heparan sulfate. Degradation of both heparan sulfate and chondroitin sulfate produced similar effects on the adherence of . However, adhesion of hyphae is not dependent on GAGs, suggesting the expression of other adhesins and the recognition of other receptors present in corneal cells. Our results open the door to new strategies for stopping the adhesion of pathogenic fungi, and their subsequent invasion of the cornea; thus, reducing the probability of the keratitis development.
真菌角膜炎最常见的病原体是属酵母菌。黏附是发病机制的第一阶段。先前的研究表明,角膜细胞表面的糖胺聚糖在细菌性角膜炎中起着至关重要的作用,尽管它们在真菌感染中的作用知之甚少。这项工作的目的是分析糖胺聚糖 (GAG) 在属真菌与角膜上皮细胞黏附中的作用。通过用特定的裂解酶进行酶消化特异性抑制这些分子的合成以及沉默参与硫酸乙酰肝素磺化的各种基因来研究 GAGs 在真菌黏附中的参与。结果似乎表明,糖胺聚糖在某种程度上充当了这种真菌的受体,尽管真菌物种之间存在差异。抑制剂处理部分降低了真菌物种的黏附。与软骨素硫酸盐相比,细胞表面硫酸乙酰肝素的消化进一步降低了 和 的黏附,表明结合主要由硫酸乙酰肝素介导。硫酸乙酰肝素和软骨素硫酸盐的降解对 的黏附均产生相似的影响。然而,菌丝的黏附不依赖于 GAGs,表明存在其他黏附素的表达和角膜细胞中存在其他受体的识别。我们的研究结果为阻止致病真菌的黏附和随后对角膜的入侵提供了新的策略;从而降低了角膜炎发展的可能性。