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SKSR1 identified as key virulence factor in Cryptosporidium by genetic crossing

Author

Listed:
  • Wei He

    (South China Agricultural University
    Shaoguan University)

  • Lianbei Sun

    (South China Agricultural University)

  • Tianyi Hou

    (South China Agricultural University)

  • Zuwei Yang

    (South China Agricultural University)

  • Fuxian Yang

    (South China Agricultural University)

  • Shengchen Zhang

    (South China Agricultural University)

  • Tianpeng Wang

    (South China Agricultural University
    Shaoguan University)

  • Xinran Wang

    (South China Agricultural University)

  • Na Li

    (South China Agricultural University)

  • Yaqiong Guo

    (South China Agricultural University)

  • L. David Sibley

    (Washington University School of Medicine)

  • Yaoyu Feng

    (South China Agricultural University)

  • Lihua Xiao

    (South China Agricultural University)

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.

Suggested Citation

  • 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, 2025. "SKSR1 identified as key virulence factor in Cryptosporidium by genetic crossing," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60088-7
    DOI: 10.1038/s41467-025-60088-7
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