Characterization of cyclophilin 23 as a novel factor for development and pathogenicity of Cryptosporidium parvum.

Abstract

Cryptosporidium parvum (C. parvum) is a common zoonotic protozoan pathogen that can cause severe diarrhea in both humans and animals. However, the factors involved in its pathogenicity remain incompletely understood. The C. parvum genome contains nine genes that encode peptidyl-prolyl cis/trans isomerases (PPIases). Previous bioinformatics analyses have indicated that proteins within this family may be associated with the pathogenicity of C. parvum. Here, we explored the role of cyclophilin 23 (CpCyP23), a member of the PPIase family, in the development and pathogenicity of C. parvum. In this study, the CpCyP23 gene was tagged and deleted using CRISPR/Cas9 technology in C. parvum. Immunofluorescence analysis demonstrated that CpCyP23 is expressed in all key developmental stages of C. parvum. The impact of CpCyP23 deficiency on parasite development and pathogenicity were assessed in HCT-8 cells and interferon-γ knockout mice, and the results revealed that the lack of CpCyP23 delayed the development of C. parvum in vitro. Moreover, compared with mice inoculated with the tagged strain, those infected with the knockout strain exhibited a reduction in parasite burden and small intestinal damage. These findings demonstrate that CpCyP23 plays a role in the development of C. parvum, and the deletion of the CpCyP23 gene reduces the pathogenicity of the C. parvum. Overall, these results advance our understanding of the pathogenic mechanisms of C. parvum and suggest CpCyP23 is a promising target for intervention in cryptosporidiosis.