Role of the Anaphase-Promoting Complex Activator Cdh1 in the Virulence of <i>Cryptococcus neoformans</i>
<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>...
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2024-12-01
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| author | Qiu-Hong Liao Lian-Tao Han Meng-Ru Guo Cheng-Li Fan Tong-Bao Liu |
| author_facet | Qiu-Hong Liao Lian-Tao Han Meng-Ru Guo Cheng-Li Fan Tong-Bao Liu |
| author_sort | Qiu-Hong Liao |
| collection | DOAJ |
| description | <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><sup>OE</sup> 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><sup>OE</sup> 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. |
| format | Article |
| id | doaj-art-c541e2a14e5848609017660b91c9a8cd |
| institution | DOAJ |
| issn | 2309-608X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Fungi |
| spelling | doaj-art-c541e2a14e5848609017660b91c9a8cd2025-08-20T02:56:48ZengMDPI AGJournal of Fungi2309-608X2024-12-01101289110.3390/jof10120891Role of the Anaphase-Promoting Complex Activator Cdh1 in the Virulence of <i>Cryptococcus neoformans</i>Qiu-Hong Liao0Lian-Tao Han1Meng-Ru Guo2Cheng-Li Fan3Tong-Bao Liu4State Key Laboratory of Resource Insects, Southwest University, Chongqing 400715, ChinaMedical Research Institute, Southwest University, Chongqing 400715, ChinaState Key Laboratory of Resource Insects, Southwest University, Chongqing 400715, ChinaCollege of Animal Science and Technology, Southwest University, Chongqing 400715, ChinaMedical Research Institute, Southwest University, Chongqing 400715, China<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><sup>OE</sup> 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><sup>OE</sup> 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.https://www.mdpi.com/2309-608X/10/12/891<i>Cryptococcus neoformans</i>APC activator Cdh1capsulevirulencechemokines |
| spellingShingle | Qiu-Hong Liao Lian-Tao Han Meng-Ru Guo Cheng-Li Fan Tong-Bao Liu Role of the Anaphase-Promoting Complex Activator Cdh1 in the Virulence of <i>Cryptococcus neoformans</i> Journal of Fungi <i>Cryptococcus neoformans</i> APC activator Cdh1 capsule virulence chemokines |
| title | Role of the Anaphase-Promoting Complex Activator Cdh1 in the Virulence of <i>Cryptococcus neoformans</i> |
| title_full | Role of the Anaphase-Promoting Complex Activator Cdh1 in the Virulence of <i>Cryptococcus neoformans</i> |
| title_fullStr | Role of the Anaphase-Promoting Complex Activator Cdh1 in the Virulence of <i>Cryptococcus neoformans</i> |
| title_full_unstemmed | Role of the Anaphase-Promoting Complex Activator Cdh1 in the Virulence of <i>Cryptococcus neoformans</i> |
| title_short | Role of the Anaphase-Promoting Complex Activator Cdh1 in the Virulence of <i>Cryptococcus neoformans</i> |
| title_sort | role of the anaphase promoting complex activator cdh1 in the virulence of i cryptococcus neoformans i |
| topic | <i>Cryptococcus neoformans</i> APC activator Cdh1 capsule virulence chemokines |
| url | https://www.mdpi.com/2309-608X/10/12/891 |
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