SKSR1 identified as key virulence factor in Cryptosporidium by genetic crossing
Abstract Cryptosporidium is a major cause of severe diarrhea. Although Cryptosporidium isolates exhibit significant differences in infectivity and virulence, the genetic determinants for these traits are not clear. In this study, we use classical genetics to cross two Cryptosporidium parvum isolates...
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| Format: | Article |
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60088-7 |
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| author | Wei He Lianbei Sun Tianyi Hou Zuwei Yang Fuxian Yang Shengchen Zhang Tianpeng Wang Xinran Wang Na Li Yaqiong Guo L. David Sibley Yaoyu Feng Lihua Xiao |
| author_facet | Wei He Lianbei Sun Tianyi Hou Zuwei Yang Fuxian Yang Shengchen Zhang Tianpeng Wang Xinran Wang Na Li Yaqiong Guo L. David Sibley Yaoyu Feng Lihua Xiao |
| author_sort | Wei He |
| collection | DOAJ |
| description | Abstract Cryptosporidium is a major cause of severe diarrhea. Although Cryptosporidium isolates exhibit significant differences in infectivity and virulence, the genetic determinants for these traits are not clear. In this study, we use classical genetics to cross two Cryptosporidium parvum isolates of different virulence and use bulk segregant analysis of whole-genome sequences from the progeny to identify quantitative trait loci (QTL) associated with Cryptosporidium infectivity and virulence. Of the 23 genes in three QTL, two have loss-of-function mutations in the low-virulence isolates, including the SKSR1 gene encoding a variant secretory protein. Deletion of the SKSR1 gene or expression of the frame-shifted sequence reduces the pathogenicity of the virulent isolate. SKSR1 is expressed in small granules and secreted into the parasite-host interface during invasion. These results demonstrate that SKSR1 is an important virulence factor in Cryptosporidium, and suggest that the extended SKSR protein family, encoded by clusters of subtelomeric genes, may contribute to pathogenesis. |
| format | Article |
| id | doaj-art-a2ead7210287457cbca5e8eca34b632c |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-a2ead7210287457cbca5e8eca34b632c2025-08-20T03:48:18ZengNature PortfolioNature Communications2041-17232025-05-0116111510.1038/s41467-025-60088-7SKSR1 identified as key virulence factor in Cryptosporidium by genetic crossingWei He0Lianbei Sun1Tianyi Hou2Zuwei Yang3Fuxian Yang4Shengchen Zhang5Tianpeng Wang6Xinran Wang7Na Li8Yaqiong Guo9L. David Sibley10Yaoyu Feng11Lihua Xiao12State 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 UniversityDepartment of Molecular Microbiology, Washington University School of MedicineState 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 Cryptosporidium is a major cause of severe diarrhea. Although Cryptosporidium isolates exhibit significant differences in infectivity and virulence, the genetic determinants for these traits are not clear. In this study, we use classical genetics to cross two Cryptosporidium parvum isolates of different virulence and use bulk segregant analysis of whole-genome sequences from the progeny to identify quantitative trait loci (QTL) associated with Cryptosporidium infectivity and virulence. Of the 23 genes in three QTL, two have loss-of-function mutations in the low-virulence isolates, including the SKSR1 gene encoding a variant secretory protein. Deletion of the SKSR1 gene or expression of the frame-shifted sequence reduces the pathogenicity of the virulent isolate. SKSR1 is expressed in small granules and secreted into the parasite-host interface during invasion. These results demonstrate that SKSR1 is an important virulence factor in Cryptosporidium, and suggest that the extended SKSR protein family, encoded by clusters of subtelomeric genes, may contribute to pathogenesis.https://doi.org/10.1038/s41467-025-60088-7 |
| spellingShingle | Wei He Lianbei Sun Tianyi Hou Zuwei Yang Fuxian Yang Shengchen Zhang Tianpeng Wang Xinran Wang Na Li Yaqiong Guo L. David Sibley Yaoyu Feng Lihua Xiao SKSR1 identified as key virulence factor in Cryptosporidium by genetic crossing Nature Communications |
| title | SKSR1 identified as key virulence factor in Cryptosporidium by genetic crossing |
| title_full | SKSR1 identified as key virulence factor in Cryptosporidium by genetic crossing |
| title_fullStr | SKSR1 identified as key virulence factor in Cryptosporidium by genetic crossing |
| title_full_unstemmed | SKSR1 identified as key virulence factor in Cryptosporidium by genetic crossing |
| title_short | SKSR1 identified as key virulence factor in Cryptosporidium by genetic crossing |
| title_sort | sksr1 identified as key virulence factor in cryptosporidium by genetic crossing |
| url | https://doi.org/10.1038/s41467-025-60088-7 |
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