Intrinsic and extrinsic factors affecting the evolution of virulence in the HIV-associated opportunistic human fungal pathogen Cryptococcus neoformans
The fungus Cryptococcus neoformans is considered the leading cause of mortality in immunocompromised patients. While extensive research has unveiled the molecular epidemiology of C. neoformans, the influence of genetic and environmental factors on genotype–phenotype correlations remains poorly under...
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| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Virulence |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/21505594.2025.2546067 |
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| author | Yuanyuan Wang Yiwu Yu Jihong Liu Linghua Li Xiaoqing Chen Sichu Xiong Yuying Pan Qinyu Tang Munika Moses Ping Zhan Guojian Liao Min Chen Liping Zhu Muyuan Li Tao Zhou Jingjun Zhao Changbin Chen |
| author_facet | Yuanyuan Wang Yiwu Yu Jihong Liu Linghua Li Xiaoqing Chen Sichu Xiong Yuying Pan Qinyu Tang Munika Moses Ping Zhan Guojian Liao Min Chen Liping Zhu Muyuan Li Tao Zhou Jingjun Zhao Changbin Chen |
| author_sort | Yuanyuan Wang |
| collection | DOAJ |
| description | The fungus Cryptococcus neoformans is considered the leading cause of mortality in immunocompromised patients. While extensive research has unveiled the molecular epidemiology of C. neoformans, the influence of genetic and environmental factors on genotype–phenotype correlations remains poorly understood. Specifically, it remains unclear whether the genetic and environmental variability observed across isolates from diverse sources has significant implications for the pathogen’s virulence. In this study, we analyzed 105 Chinese C. neoformans isolates, including 54 from HIV-infected patients, 44 from HIV-uninfected individuals and seven from a natural environment. Multilocus sequence typing (MLST) revealed that sequence type (ST) 5 predominates across all clinical isolates; however, genotypic diversity was notably higher in isolates from HIV-uninfected individuals and the natural environment, whereas HIV-infected isolates exhibited restricted genetic variation. Furthermore, isolates from HIV-uninfected individuals exhibited significantly enhanced virulence traits, including elevated capsule production, increased melanin production, improved survival in human cerebrospinal fluid (CSF), reduced phagocytic uptake, and higher mortality in both Galleria mellonella and murine models of cryptococcosis. Importantly, these pathogenic phenotypes were correlated with CD4+ T cell counts, highlighting the critical role of host immunity in shaping C. neoformans virulence. Whole-genome sequencing and genome-wide association studies (GWAS) further revealed that variations in genes involved in carbohydrate metabolism, such as CDA3 and GPD1, may drive host-specific virulence evolution. Our results support a genotype–phenotype correlation, demonstrating that both genetic and environmental factors shape the virulence of C. neoformans, with significant implications for understanding host–pathogen interactions and guiding therapeutic strategies. |
| format | Article |
| id | doaj-art-113bd2c2e5c24fe795b934b3b37856f3 |
| institution | Kabale University |
| issn | 2150-5594 2150-5608 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Virulence |
| spelling | doaj-art-113bd2c2e5c24fe795b934b3b37856f32025-08-20T04:01:01ZengTaylor & Francis GroupVirulence2150-55942150-56082025-12-0116110.1080/21505594.2025.2546067Intrinsic and extrinsic factors affecting the evolution of virulence in the HIV-associated opportunistic human fungal pathogen Cryptococcus neoformansYuanyuan Wang0Yiwu Yu1Jihong Liu2Linghua Li3Xiaoqing Chen4Sichu Xiong5Yuying Pan6Qinyu Tang7Munika Moses8Ping Zhan9Guojian Liao10Min Chen11Liping Zhu12Muyuan Li13Tao Zhou14Jingjun Zhao15Changbin Chen16Joint Laboratory for Biomedical Research and Pharmaceutical Innovation, Unit of Pathogenic Fungal Infection & Host Immunity, Key Laboratory of Molecular Virology and Immunology, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, ChinaDepartment of Dermatology, Tongji Hospital, Tongji University School of Medicine, Shanghai, ChinaJoint Laboratory for Biomedical Research and Pharmaceutical Innovation, Unit of Pathogenic Fungal Infection & Host Immunity, Key Laboratory of Molecular Virology and Immunology, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, ChinaInstitute of Infectious Disease, Guangzhou No.8 People’s Hospital, Guangzhou, ChinaJoint Laboratory for Biomedical Research and Pharmaceutical Innovation, Unit of Pathogenic Fungal Infection & Host Immunity, Key Laboratory of Molecular Virology and Immunology, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, ChinaJoint Laboratory for Biomedical Research and Pharmaceutical Innovation, Unit of Pathogenic Fungal Infection & Host Immunity, Key Laboratory of Molecular Virology and Immunology, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, ChinaJoint Laboratory for Biomedical Research and Pharmaceutical Innovation, Unit of Pathogenic Fungal Infection & Host Immunity, Key Laboratory of Molecular Virology and Immunology, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, ChinaDepartment of Dermatology, Tongji Hospital, Tongji University School of Medicine, Shanghai, ChinaJoint Laboratory for Biomedical Research and Pharmaceutical Innovation, Unit of Pathogenic Fungal Infection & Host Immunity, Key Laboratory of Molecular Virology and Immunology, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, ChinaSeventh People’s Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaCollege of Pharmaceutical Sciences, Southwest University, Chongqing, ChinaDepartment of Dermatology, Shanghai Key Laboratory of Medical Mycology, Changzheng Hospital, Second Military Medical University, Shanghai, ChinaDepartment of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, ChinaCollege of Pharmaceutical Sciences, Southwest University, Chongqing, ChinaCollege of Pharmaceutical Sciences, Southwest University, Chongqing, ChinaDepartment of Dermatology, Tongji Hospital, Tongji University School of Medicine, Shanghai, ChinaJoint Laboratory for Biomedical Research and Pharmaceutical Innovation, Unit of Pathogenic Fungal Infection & Host Immunity, Key Laboratory of Molecular Virology and Immunology, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, ChinaThe fungus Cryptococcus neoformans is considered the leading cause of mortality in immunocompromised patients. While extensive research has unveiled the molecular epidemiology of C. neoformans, the influence of genetic and environmental factors on genotype–phenotype correlations remains poorly understood. Specifically, it remains unclear whether the genetic and environmental variability observed across isolates from diverse sources has significant implications for the pathogen’s virulence. In this study, we analyzed 105 Chinese C. neoformans isolates, including 54 from HIV-infected patients, 44 from HIV-uninfected individuals and seven from a natural environment. Multilocus sequence typing (MLST) revealed that sequence type (ST) 5 predominates across all clinical isolates; however, genotypic diversity was notably higher in isolates from HIV-uninfected individuals and the natural environment, whereas HIV-infected isolates exhibited restricted genetic variation. Furthermore, isolates from HIV-uninfected individuals exhibited significantly enhanced virulence traits, including elevated capsule production, increased melanin production, improved survival in human cerebrospinal fluid (CSF), reduced phagocytic uptake, and higher mortality in both Galleria mellonella and murine models of cryptococcosis. Importantly, these pathogenic phenotypes were correlated with CD4+ T cell counts, highlighting the critical role of host immunity in shaping C. neoformans virulence. Whole-genome sequencing and genome-wide association studies (GWAS) further revealed that variations in genes involved in carbohydrate metabolism, such as CDA3 and GPD1, may drive host-specific virulence evolution. Our results support a genotype–phenotype correlation, demonstrating that both genetic and environmental factors shape the virulence of C. neoformans, with significant implications for understanding host–pathogen interactions and guiding therapeutic strategies.https://www.tandfonline.com/doi/10.1080/21505594.2025.2546067Cryptococcus neoformansvirulencegenotype-phenotype correlationenvironmental factorsgenetic variants |
| spellingShingle | Yuanyuan Wang Yiwu Yu Jihong Liu Linghua Li Xiaoqing Chen Sichu Xiong Yuying Pan Qinyu Tang Munika Moses Ping Zhan Guojian Liao Min Chen Liping Zhu Muyuan Li Tao Zhou Jingjun Zhao Changbin Chen Intrinsic and extrinsic factors affecting the evolution of virulence in the HIV-associated opportunistic human fungal pathogen Cryptococcus neoformans Virulence Cryptococcus neoformans virulence genotype-phenotype correlation environmental factors genetic variants |
| title | Intrinsic and extrinsic factors affecting the evolution of virulence in the HIV-associated opportunistic human fungal pathogen Cryptococcus neoformans |
| title_full | Intrinsic and extrinsic factors affecting the evolution of virulence in the HIV-associated opportunistic human fungal pathogen Cryptococcus neoformans |
| title_fullStr | Intrinsic and extrinsic factors affecting the evolution of virulence in the HIV-associated opportunistic human fungal pathogen Cryptococcus neoformans |
| title_full_unstemmed | Intrinsic and extrinsic factors affecting the evolution of virulence in the HIV-associated opportunistic human fungal pathogen Cryptococcus neoformans |
| title_short | Intrinsic and extrinsic factors affecting the evolution of virulence in the HIV-associated opportunistic human fungal pathogen Cryptococcus neoformans |
| title_sort | intrinsic and extrinsic factors affecting the evolution of virulence in the hiv associated opportunistic human fungal pathogen cryptococcus neoformans |
| topic | Cryptococcus neoformans virulence genotype-phenotype correlation environmental factors genetic variants |
| url | https://www.tandfonline.com/doi/10.1080/21505594.2025.2546067 |
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