Abstract

Cryptococcus neoformansis 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 inC. neoformans. Deletion or overexpression of theVLP1gene results in abnormal capsule formation and melanin production ofC. neoformans. Stress tolerance assay showed that thevlp1Δ mutant was sensitive to SDS and NaCl but not to CFW or Congo red, indicating that Vlp1 might regulate the cell membrane integrity inC. neoformans. Fungal virulence assay showed that Vlp1 was essential for the pathogenicity ofC. neoformans, asvlp1Δ mutants are avirulent in the mouse systematic infection model of cryptococcosis. The progression of fungal infection revealed that thevlp1Δ mutants were gradually eliminated from the lungs of the mice after infection. Moreover, thevlp1Δ mutants showed a proliferation defect inside macrophages and a viability defect in the host complement system, which likely contributes to the virulence attenuation of thevlp1Δ mutants. In summary, our results revealed that the vacuolar morphogenesis protein Vam6-like protein Vlp1 is essential for the pathogenicity ofC. neoformans.Keywords:Cryptococcus neoformans;vacuolar morphogenesis protein;Vlp1;virulence;macrophage