Pereira de Mello Thaís, A Silva Bianca, Lione Viviane, Devereux Michael, McCann Malachy, Branquinha Marta Helena, Luis Souza Dos Santos André
Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes (LEAMER), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes (IMPG), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.
Instituto de Saúde de Nova Friburgo, Universidade Federal Fluminense (UFF), Nova Friburgo, Rio de Janeiro, Brazil.
Curr Top Med Chem. 2025 Jan 1. doi: 10.2174/0115680266327984241018111547.
Scedosporium apiospermum is a multidrug-resistant filamentous fungus that causes localized and disseminated diseases. Our group has previously described that metalbased complexes containing copper(II) or silver(I) ions complexed with 1,10-phenanthroline-5,6- dione (phendione) inhibited the viability of S. apiospermum conidial cells.
The effects of these promising complexes, Cu(phendione)32.4H2O (Cuphendione) and [Ag(phendione)2]ClO4 (Ag-phendione), on vital biological processes, production of key virulence attributes and interaction events of S. apiospermum were investigated using a comprehensive multimodal approach.
The results demonstrated that both Cu-phendione and Ag-phendione effectively inhibited the viability of S. apiospermum mycelial cells in a dose-dependent manner. Furthermore, these test complexes, at varying concentrations, inhibited the transition of S. apiospermum conidia into hyphae. Scanning electron microscopy revealed significant structural alterations in the fungal cells, including changes to surface sculpturing and overall morphological architecture, following treatment with the complexes. A marked reduction in the expression of key surface molecules, such as mannose/glucose-rich glycoconjugates, fibronectin-binding proteins, and the well-known adhesin peptidorhamnomannan further supported these ultrastructural changes. The treatment also impaired adhesive interactions, reducing the fungus's ability to form biofilms on polystyrene surfaces and diminishing its interaction with macrophages, lung epithelial cells, and fibroblasts. Notably, treatment of infected macrophages with the complexes led to a significant reduction in the number of intracellular fungal cells.
The results provide information about the effects of silver- and copper-phendione complexes on cellular and virulence aspects of the emerging fungus S. apiospermum.
伪阿利什霉是一种多重耐药丝状真菌，可引起局部和播散性疾病。我们团队之前曾描述过，含有与1,10-菲咯啉-5,6-二酮（菲咯二酮）络合的铜（II）或银（I）离子的金属基络合物可抑制伪阿利什霉分生孢子细胞的活力。
采用综合多模态方法研究这些有前景的络合物，即Cu（菲咯二酮）32·4H2O（铜菲咯二酮）和[Ag（菲咯二酮）2]ClO4（银菲咯二酮）对伪阿利什霉重要生物学过程、关键毒力属性产生及相互作用事件的影响。
结果表明，铜菲咯二酮和银菲咯二酮均能以剂量依赖方式有效抑制伪阿利什霉菌丝细胞的活力。此外，这些测试络合物在不同浓度下均能抑制伪阿利什霉分生孢子向菌丝的转变。扫描电子显微镜显示，用络合物处理后，真菌细胞出现明显的结构改变，包括表面纹饰和整体形态结构的变化。关键表面分子，如富含甘露糖/葡萄糖的糖缀合物、纤连蛋白结合蛋白以及著名的粘附素肽聚糖的表达显著降低，进一步支持了这些超微结构变化。该处理还损害了粘附相互作用，降低了真菌在聚苯乙烯表面形成生物膜的能力，并减少了其与巨噬细胞、肺上皮细胞和成纤维细胞的相互作用。值得注意的是，用络合物处理感染的巨噬细胞可导致细胞内真菌细胞数量显著减少。
这些结果提供了有关银-菲咯二酮和铜-菲咯二酮络合物对新兴真菌伪阿利什霉的细胞和毒力方面影响的信息。
