Sun Xun, Wang Yueqing, Yang Xiaomin, Xiang Xi, Zou Lili, Liu Xiaowen, Luo Gang, Han Qi
School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China.
The Third Clinical Medical College of the Three Gorges University, Gezhouba Central Hospital of Sinopharm, Yichang, Hubei, China.
Microbiol Spectr. 2025 Apr;13(4):e0259324. doi: 10.1128/spectrum.02593-24. Epub 2025 Feb 24.
Profilin is a small actin-binding protein that plays an important role in actin polymerization. However, its functions in , the most prevalent fungal pathogen, remain unclear. Here, we report that profilin plays a crucial role in morphogenesis and virulence. Deletion of profilin results in abnormal morphogenesis and impaired hyphal development. Furthermore, is hypersensitive to cell wall stress and displays thicker cell wall than wild-type cells, indicative of a critical function of Pfy1 in cell wall integrity. In addition, our findings demonstrate that profilin is required for the virulence of in a murine model of systemic infection. In conclusion, our work provides a promising target for developing antifungal drugs.IMPORTANCEOur research revealed Pfy1 is not only involved in hyphal development but also essential for pseudohyphal formation in response to DNA damage agents methyl methanesulfonate (MMS) and HO The disruption of resulted in striking morphological defects in both yeast and hyphal forms. Further investigation suggested that profilin plays a role in polarized growth of via binding with Act1, and contributes to cell wall remodeling. Both hyphal growth and cell wall integrity are the important virulence factors of . Thus, strains significantly reduced mortality rates in mice. These findings suggested that profilin could serve as a target for developing new antifungal drugs possibly for use in combination therapies with caspofungin, for treating invasive candidiasis.
丝切蛋白是一种小的肌动蛋白结合蛋白，在肌动蛋白聚合中起重要作用。然而，它在最常见的真菌病原体中的功能仍不清楚。在此，我们报道丝切蛋白在形态发生和毒力中起关键作用。丝切蛋白的缺失导致形态发生异常和菌丝发育受损。此外，该病原体对细胞壁应激高度敏感，并且显示出比野生型细胞更厚的细胞壁，这表明Pfy1在细胞壁完整性中具有关键功能。此外，我们的研究结果表明，在系统性感染的小鼠模型中，丝切蛋白是该病原体毒力所必需的。总之，我们的工作为开发抗真菌药物提供了一个有前景的靶点。重要性我们的研究表明，Pfy1不仅参与菌丝发育，而且对于响应DNA损伤剂甲磺酸甲酯（MMS）和HO形成假菌丝也至关重要。该病原体的破坏导致酵母和菌丝形式都出现明显的形态缺陷。进一步的研究表明，丝切蛋白通过与Act1结合在该病原体的极性生长中起作用，并有助于细胞壁重塑。菌丝生长和细胞壁完整性都是该病原体的重要毒力因子。因此，该病原体菌株显著降低了小鼠的死亡率。这些发现表明，丝切蛋白可以作为开发新抗真菌药物的靶点，可能与卡泊芬净联合用于治疗侵袭性念珠菌病。
