The Vacuolar Morphogenesis Protein Vam6-Like Protein Vlp1 Is Required for Pathogenicity of Cryptococcus neoformans

Cryptococcus neoformans is an encapsulated yeast pathogen that infects immunocompromised patients to cause fungal meningitis, resulting in hundreds of thousands of deaths each year. F-box protein Fbp1, the key component of the E3 ubiquitin ligase, plays a critical role in fungal development and virulence in fungal pathogens. In this study, we identified a potential substrate of Fbp1, the vacuolar morphogenesis protein Vam6-like protein Vlp1, and evaluated its role in virulence in C. neoformans. Deletion or overexpression of the VLP1 gene results in abnormal capsule formation and melanin production of C. neoformans. Stress tolerance assay showed that the vlp1 Delta mutant was sensitive to SDS and NaCl but not to CFW or Congo red, indicating that Vlp1 might regulate the cell membrane integrity in C. neoformans. Fungal virulence assay showed that Vlp1 was essential for the pathogenicity of C. neoformans, as vlp1 Delta mutants are avirulent in the mouse systematic infection model of cryptococcosis. The progression of fungal infection revealed that the vlp1 Delta mutants were gradually eliminated from the lungs of the mice after infection. Moreover, the vlp1 Delta mutants showed a proliferation defect inside macrophages and a viability defect in the host complement system, which likely contributes to the virulence attenuation of the vlp1 Delta mutants. In summary, our results revealed that the vacuolar morphogenesis protein Vam6-like protein Vlp1 is essential for the pathogenicity of C. neoformans.

Automated summary

The study identified the vacuolar morphogenesis protein Vam6-like protein Vlp1 as essential for the pathogenicity of Cryptococcus neoformans. Deletion of the VLP1 gene resulted in abnormal capsule formation and melanin production of C. neoformans, and stress tolerance assays indicated that Vlp1 may regulate cell membrane integrity. Moreover, vlp1 Delta mutants exhibited decreased virulence in a mouse systematic infection model of cryptococcosis, suggesting an important role of Vlp1 in fungal pathogenicity.