Department of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Kraków, Poland.
Doctoral School of Exact and Natural Sciences, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Kraków, Poland.
Int J Mol Sci. 2024 Apr 27;25(9):4775. doi: 10.3390/ijms25094775.
Extracellular proteases are key factors contributing to the virulence of pathogenic fungi from the genus . Their proteolytic activities are crucial for extracting nutrients from the external environment, degrading host defenses, and destabilizing the internal balance of the human organism. Currently, the enzymes most frequently described in this context are secreted aspartic proteases (Saps). This review comprehensively explores the multifaceted roles of Saps, highlighting their importance in biofilm formation, tissue invasion through the degradation of extracellular matrix proteins and components of the coagulation cascade, modulation of host immune responses via impairment of neutrophil and monocyte/macrophage functions, and their contribution to antifungal resistance. Additionally, the diagnostic challenges associated with infections and the potential of Saps as biomarkers were discussed. Furthermore, we examined the prospects of developing vaccines based on Saps and the use of protease inhibitors as adjunctive therapies for candidiasis. Given the complex biology of Saps and their central role in pathogenicity, a multidisciplinary approach may pave the way for innovative diagnostic strategies and open new opportunities for innovative clinical interventions against candidiasis.
细胞外蛋白酶是致病真菌属的关键毒力因子。它们的蛋白水解活性对于从外部环境中提取营养物质、降解宿主防御和破坏人体内部平衡至关重要。目前,在这种情况下最常描述的酶是分泌天冬氨酸蛋白酶(Saps)。这篇综述全面探讨了 Saps 的多方面作用,强调了它们在生物膜形成、通过降解细胞外基质蛋白和凝血级联成分进行组织侵袭、通过损害中性粒细胞和单核细胞/巨噬细胞功能调节宿主免疫反应以及对抗真菌耐药性的贡献。此外,还讨论了与感染相关的诊断挑战以及 Saps 作为生物标志物的潜力。此外,我们研究了基于 Saps 开发疫苗以及使用蛋白酶抑制剂作为念珠菌病辅助治疗的前景。鉴于 Saps 的复杂生物学及其在致病性中的核心作用,多学科方法可能为创新的诊断策略铺平道路,并为针对念珠菌病的创新临床干预提供新的机会。