Role of the Anaphase-Promoting Complex Activator Cdh1 in the Virulence of Cryptococcus neoformans

<i>Cryptococcus neoformans</i> is a globally distributed human fungal pathogen that can cause cryptococcal meningitis with high morbidity and mortality. In this study, we identified an anaphase-promoting complex (APC) activator, Cdh1, and examined its impact on the virulence of <i>C. neoformans</i>. Our subcellular localization analysis revealed that Cdh1 is situated in the nucleus of <i>C. neoformans</i>. Disrupting or overexpressing the <i>CDH1</i> gene caused abnormal capsule formation in <i>C. neoformans</i>. The <i>cdh1</i>Δ mutant displayed slight sensitivity when grown at 37 °C, indicating that Cdh1 plays a role in maintaining the growth of <i>C. neoformans</i> at 37 °C. A fungal virulence assay showed that Cdh1 is closely associated with the virulence of <i>C. neoformans</i>, and both the <i>cdh1</i>Δ mutant and <i>CDH1</i>^OE overexpression strains significantly diminished the virulence of <i>C. neoformans</i>. The <i>Cryptococcus</i>-macrophage interaction assay revealed that both the <i>cdh1</i>∆ mutant and the <i>CDH1</i>^OE strains had significantly lower proliferation ability inside macrophages. Furthermore, the infection of the <i>cdh1</i>Δ mutant significantly activated neutrophil recruitment, as well as Th2 and Th17 immune responses, in lung tissue. In summary, our findings indicate that Cdh1 is crucial for producing virulence factors and fungal virulence in <i>C. neoformans</i>. The findings of this study can offer valuable insights and form the basis for further study of the regulatory mechanisms governing the pathogenicity of <i>C. neoformans</i>, potentially leading to the development of novel therapeutic strategies.