Profilin Pfy1 is critical for cell wall integrity and virulence in Candida albicans.

Profilin is a small actin-binding protein that plays an important role in actin polymerization. However, its functions in Candida albicans, the most prevalent fungal pathogen, remain unclear. Here, we report that profilin plays a crucial role in C. albicans morphogenesis and virulence. Deletion of profilin results in abnormal morphogenesis and impaired hyphal development. Furthermore, pfy1Δ/Δ 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 C. albicans 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 H2O2. The disruption of PFY1 resulted in striking morphological defects in both yeast and hyphal forms. Further investigation suggested that profilin plays a role in polarized growth of Candida albicans via binding with Act1, and contributes to cell wall remodeling. Both hyphal growth and cell wall integrity are the important virulence factors of C. albicans. Thus, pfy1Δ/Δ 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.