Requirement of Toxoplasma gondii metacaspases for IMC1 maturation, endodyogeny and virulence in mice
| Autor: | Xiaodong Sun, Qun Liu, Muzi Li, Yayun Wu, Jing Liu, Yihan Wu, Yong Fu, Xiao Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Transgene Foreskin Protozoan Proteins Virulence Toxoplasma gondii Infectious and parasitic diseases RC109-216 Microbiology Mice Inner membrane complex 1 Chlorocebus aethiops Maturation Animals Humans Endodyogeny Vero Cells Metacaspases Mice Inbred BALB C Inner membrane complex biology Strain (chemistry) Cell growth Research Fibroblasts biology.organism_classification In vitro Infectious Diseases Caspases Protozoa Female Parasitology Toxoplasma |
| Zdroj: | Parasites & Vectors, Vol 14, Iss 1, Pp 1-11 (2021) Parasites & Vectors |
| ISSN: | 1756-3305 |
| Popis: | BackgroundMetacaspases are multifunctional proteins found in plants, fungi and protozoa, and are involved in processes such as insoluble protein aggregate clearance and cell proliferation. Our previous study demonstrated that metacaspase-1 (MCA1) contributes to parasite apoptosis inToxoplasma gondii. Deletion of MCA1 fromT. gondiihas no effect on the growth and virulence of the parasites. Three metacaspases were identified in the ToxoDBToxoplasmaInformatics Resource, and the function of metacaspase-2 (MCA2) and metacaspase-3 (MCA3) has not been demonstrated.MethodsIn this study, we constructed MCA1, MCA2 and MCA1/MCA2 transgenic strains from RHΔku80 (Δku80), including overexpressing strains and knockout strains, to clarify the function of MCA1 and MCA2 ofT. gondii.ResultsMCA1 and MCA2 were distributed in the cytoplasm with punctuated aggregation, and part of the punctuated aggregation of MCA1 and MCA2 was localized on the inner membrane complex ofT. gondii. The proliferation of the MCA1/MCA2 double-knockout strain was significantly reduced; however, the two single knockout strains (MCA1 knockout strain and MCA2 knockout strain) exhibited normal growth rates as compared to the parental strain, Δku80. In addition, endodyogeny was impaired in the tachyzoites whose MCA1 and MCA2 were both deleted due to multiple nuclei and abnormal expression of IMC1. We further found that IMC1 of the double-knockout strain was detergent-soluble, indicating that MCA1 and MCA2 are associated with IMC1 maturation. Compared to the parental Δku80 strain, the double-knockout strain was more readily induced from tachyzoites to bradyzoites in vitro. Furthermore, the double-knockout strain was less pathogenic in mice and was able to develop bradyzoites in the brain, which formed cysts and established chronic infection.ConclusionMCA1 and MCA2 are important factors which participate in IMC1 maturation and endodyogeny ofT. gondii. The double-knockout strain has slower proliferation and was able to develop bradyzoites both in vitro and in vivo.Graphic abstract |
| Databáze: | OpenAIRE |
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