Liao Qiu-Hong, Han Lian-Tao, Guo Meng-Ru, Fan Cheng-Li, Liu Tong-Bao
State Key Laboratory of Resource Insects, Southwest University, Chongqing 400715, China.
Medical Research Institute, Southwest University, Chongqing 400715, China.
J Fungi (Basel). 2024 Dec 23;10(12):891. doi: 10.3390/jof10120891.
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 . Our subcellular localization analysis revealed that Cdh1 is situated in the nucleus of . Disrupting or overexpressing the gene caused abnormal capsule formation in . The Δ mutant displayed slight sensitivity when grown at 37 °C, indicating that Cdh1 plays a role in maintaining the growth of at 37 °C. A fungal virulence assay showed that Cdh1 is closely associated with the virulence of , and both the Δ mutant and overexpression strains significantly diminished the virulence of . The -macrophage interaction assay revealed that both the ∆ mutant and the strains had significantly lower proliferation ability inside macrophages. Furthermore, the infection of the 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 . The findings of this study can offer valuable insights and form the basis for further study of the regulatory mechanisms governing the pathogenicity of , potentially leading to the development of novel therapeutic strategies.
是一种全球分布的人类真菌病原体，可引起发病率和死亡率很高的隐球菌性脑膜炎。在本研究中，我们鉴定了一种后期促进复合体（APC）激活剂Cdh1，并研究了其对……毒力的影响。我们的亚细胞定位分析表明，Cdh1位于……的细胞核中。破坏或过表达……基因导致……中出现异常的荚膜形成。Δ突变体在37℃生长时表现出轻微的敏感性，表明Cdh1在维持……在37℃的生长中起作用。一项真菌毒力试验表明，Cdh1与……的毒力密切相关，Δ突变体和……过表达菌株均显著降低了……的毒力。……与巨噬细胞相互作用试验表明，Δ突变体和……菌株在巨噬细胞内的增殖能力均显著降低。此外，Δ突变体的感染显著激活了肺组织中的中性粒细胞募集以及Th2和Th17免疫反应。总之，我们的研究结果表明，Cdh1对于……中产生毒力因子和真菌毒力至关重要。本研究结果可为深入了解……致病性的调控机制提供有价值的见解，并为进一步研究奠定基础，并有可能导致新治疗策略的开发。
