Multicopy subtelomeric genes underlie animal infectivity of divergent Cryptosporidium hominis subtypes
Abstract The anthroponotic Cryptosporidium hominis differs from the zoonotic C. parvum in its lack of infectivity to animals, but several divergent subtypes have recently been found in nonhuman primates and equines. Here, we sequence 17 animal C. hominis isolates and generate a new IbA12G3 genome at...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54995-4 |
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| author | Wanyi Huang Wei He Yue Huang Yongping Tang Ming Chen Lianbei Sun Zuwei Yang Tianyi Hou Huimin Liu Haoyu Chen Tianpeng Wang Na Li Yaqiong Guo Lihua Xiao Yaoyu Feng |
| author_facet | Wanyi Huang Wei He Yue Huang Yongping Tang Ming Chen Lianbei Sun Zuwei Yang Tianyi Hou Huimin Liu Haoyu Chen Tianpeng Wang Na Li Yaqiong Guo Lihua Xiao Yaoyu Feng |
| author_sort | Wanyi Huang |
| collection | DOAJ |
| description | Abstract The anthroponotic Cryptosporidium hominis differs from the zoonotic C. parvum in its lack of infectivity to animals, but several divergent subtypes have recently been found in nonhuman primates and equines. Here, we sequence 17 animal C. hominis isolates and generate a new IbA12G3 genome at the chromosome level. Comparative analysis with 222 human isolates shows significant genetic divergence of the animal isolates, with genetic recombination among them. They have additional subtelomeric insulinase and MEDLE genes. In interferon-γ knockout mice, three monkey isolates show differences in infectivity and induce higher and longer oocyst shedding than a reference C. parvum isolate. Deletion of the MEDLE genes significantly reduces the growth and pathogenicity of a virulent strain in mice. Co-infection of two fluorescence-tagged C. hominis subtypes produces bicolored oocysts, supporting the conclusion that mixed subtype infections can lead to genetic recombination. These data provide insight into potential determinants of host infectivity in Cryptosporidium, and a convenient animal model for biological studies of C. hominis. |
| format | Article |
| id | doaj-art-cd6a6b0ec37b4331b2eb3f880f18f842 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-cd6a6b0ec37b4331b2eb3f880f18f8422025-01-05T12:35:59ZengNature PortfolioNature Communications2041-17232024-12-0115111710.1038/s41467-024-54995-4Multicopy subtelomeric genes underlie animal infectivity of divergent Cryptosporidium hominis subtypesWanyi Huang0Wei He1Yue Huang2Yongping Tang3Ming Chen4Lianbei Sun5Zuwei Yang6Tianyi Hou7Huimin Liu8Haoyu Chen9Tianpeng Wang10Na Li11Yaqiong Guo12Lihua Xiao13Yaoyu Feng14State Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural UniversityState Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural UniversityState Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural UniversityState Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural UniversityState Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural UniversityState Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural UniversityState Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural UniversityState Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural UniversityState Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural UniversityState Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural UniversityState Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural UniversityState Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural UniversityState Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural UniversityState Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural UniversityState Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural UniversityAbstract The anthroponotic Cryptosporidium hominis differs from the zoonotic C. parvum in its lack of infectivity to animals, but several divergent subtypes have recently been found in nonhuman primates and equines. Here, we sequence 17 animal C. hominis isolates and generate a new IbA12G3 genome at the chromosome level. Comparative analysis with 222 human isolates shows significant genetic divergence of the animal isolates, with genetic recombination among them. They have additional subtelomeric insulinase and MEDLE genes. In interferon-γ knockout mice, three monkey isolates show differences in infectivity and induce higher and longer oocyst shedding than a reference C. parvum isolate. Deletion of the MEDLE genes significantly reduces the growth and pathogenicity of a virulent strain in mice. Co-infection of two fluorescence-tagged C. hominis subtypes produces bicolored oocysts, supporting the conclusion that mixed subtype infections can lead to genetic recombination. These data provide insight into potential determinants of host infectivity in Cryptosporidium, and a convenient animal model for biological studies of C. hominis.https://doi.org/10.1038/s41467-024-54995-4 |
| spellingShingle | Wanyi Huang Wei He Yue Huang Yongping Tang Ming Chen Lianbei Sun Zuwei Yang Tianyi Hou Huimin Liu Haoyu Chen Tianpeng Wang Na Li Yaqiong Guo Lihua Xiao Yaoyu Feng Multicopy subtelomeric genes underlie animal infectivity of divergent Cryptosporidium hominis subtypes Nature Communications |
| title | Multicopy subtelomeric genes underlie animal infectivity of divergent Cryptosporidium hominis subtypes |
| title_full | Multicopy subtelomeric genes underlie animal infectivity of divergent Cryptosporidium hominis subtypes |
| title_fullStr | Multicopy subtelomeric genes underlie animal infectivity of divergent Cryptosporidium hominis subtypes |
| title_full_unstemmed | Multicopy subtelomeric genes underlie animal infectivity of divergent Cryptosporidium hominis subtypes |
| title_short | Multicopy subtelomeric genes underlie animal infectivity of divergent Cryptosporidium hominis subtypes |
| title_sort | multicopy subtelomeric genes underlie animal infectivity of divergent cryptosporidium hominis subtypes |
| url | https://doi.org/10.1038/s41467-024-54995-4 |
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