A Carbamoyl Phosphate Synthetase II (CPSII) Deletion Mutant of Toxoplasma gondii Induces Partial Protective Immunity in Mice
is an obligate intracellular protozoan parasite. primarily infection in pregnant women may result in fetal abortion, and infection in immunosuppressed population may result in toxoplasmosis. Carbamoyl phosphate synthetase II (CPSII) is a key enzyme in the pyrimidine-biosynthesis pathway, and has a c...
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Published in | Frontiers in microbiology Vol. 11; p. 616688 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
14.01.2021
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Subjects | |
Online Access | Get full text |
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Summary: | is an obligate intracellular protozoan parasite.
primarily infection in pregnant women may result in fetal abortion, and infection in immunosuppressed population may result in toxoplasmosis. Carbamoyl phosphate synthetase II (CPSII) is a key enzyme in the
pyrimidine-biosynthesis pathway, and has a crucial role in parasite replication. We generated a mutant with complete deletion of CPSII via clustered regularly interspaced short palindromic repeats (CRISPR)/cas9 in type-1 RH strain of
. We tested the intracellular proliferation of this mutant and found that it showed significantly reduced replication
, though CPSII deletion did not completely stop the parasite growth. The immune responses induced by the infection of RHΔCPSII tachyzoites in mice were evaluated. During infection in mice, the RHΔCPSII mutant displayed notable defects in replication and virulence, and significantly enhanced the survival of mice compared with survival of RH-infected mice. We tracked parasite propagation from ascitic fluid in mice infected with the RHΔCPSII mutant, and few tachyzoites were observed at early infection. We also observed that the RHΔCPSII mutant induced greater accumulation of neutrophils. The mutant induced a higher level of T-helper type-1 cytokines [interferon (IFN)-γ, interleukin (IL)-12]. The mRNA levels of signal transducer and activator of transcription cellular transcription factor 1 and IFN regulatory factor 8 were significantly higher in the RHΔCPSII mutant-infected group. Together, these data suggest that CPSII is crucial for parasite growth, and that strains lack the
pyrimidine biosynthesis pathway and salvage pathway may become a promising live attenuated vaccine to prevent infection with
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Chuan Su, Nanjing Medical University, China; Qijun Chen, Shenyang Agricultural University, China; Jilong Shen, Anhui Medical University, China Edited by: Hong-Juan Peng, Southern Medical University, China This article was submitted to Infectious Diseases, a section of the journal Frontiers in Microbiology These authors have contributed equally to this work |
ISSN: | 1664-302X 1664-302X |
DOI: | 10.3389/fmicb.2020.616688 |