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The Role of Type II Fatty Acid Synthesis Enzymes FabZ, ODSCI, and ODSCII in the Pathogenesis of Toxoplasma gondii Infection

Toxoplasma gondii is an obligate intracellular protozoan parasite, which has a worldwide distribution and can infect a large number of warm-blooded animals and humans. T. gondii must colonize and proliferate inside the host cells in order to maintain its own survival by securing essential nutrients...

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Autores principales: Xu, Xiao-Pei, Elsheikha, Hany M., Liu, Wen-Ge, Zhang, Zhi-Wei, Sun, Li-Xiu, Liang, Qin-Li, Song, Ming-Xin, Zhu, Xing-Quan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438308/
https://www.ncbi.nlm.nih.gov/pubmed/34531837
http://dx.doi.org/10.3389/fmicb.2021.703059
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author Xu, Xiao-Pei
Elsheikha, Hany M.
Liu, Wen-Ge
Zhang, Zhi-Wei
Sun, Li-Xiu
Liang, Qin-Li
Song, Ming-Xin
Zhu, Xing-Quan
author_facet Xu, Xiao-Pei
Elsheikha, Hany M.
Liu, Wen-Ge
Zhang, Zhi-Wei
Sun, Li-Xiu
Liang, Qin-Li
Song, Ming-Xin
Zhu, Xing-Quan
author_sort Xu, Xiao-Pei
collection PubMed
description Toxoplasma gondii is an obligate intracellular protozoan parasite, which has a worldwide distribution and can infect a large number of warm-blooded animals and humans. T. gondii must colonize and proliferate inside the host cells in order to maintain its own survival by securing essential nutrients for the development of the newly generated tachyzoites. The type II fatty acid biosynthesis pathway (FASII) in the apicoplast is essential for the growth and survival of T. gondii. We investigated whether deletion of genes in the FASII pathway influences the in vitro growth and in vivo virulence of T. gondii. We focused on beta-hydroxyacyl-acyl carrier protein dehydratase (FabZ) and oxidoreductase, short chain dehydrogenase/reductase family proteins ODSCI and ODSCII. We constructed T. gondii strains deficient in FabZ, ODSCI, and ODSCII using CRISPR-Cas9 gene editing technology. The results of immunofluorescence assay, plaque assay, proliferation assay and egress assay showed that in RHΔFabZ strain the apicoplast was partly lost and the growth ability of the parasite in vitro was significantly inhibited, while for RHΔODSCI and RHΔODSCII mutant strains no similar changes were detected. RHΔFabZ exhibited reduced virulence for mice compared with RHΔODSCI and RHΔODSCII, as shown by the improved survival rate. Deletion of FabZ in the PRU strain significantly decreased the brain cyst burden in mice compared with PRUΔODSCI and PRUΔODSCII. Collectively, these findings suggest that FabZ contributes to the growth and virulence of T. gondii, while ODSCI and ODSCII do not contribute to these traits.
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spelling pubmed-84383082021-09-15 The Role of Type II Fatty Acid Synthesis Enzymes FabZ, ODSCI, and ODSCII in the Pathogenesis of Toxoplasma gondii Infection Xu, Xiao-Pei Elsheikha, Hany M. Liu, Wen-Ge Zhang, Zhi-Wei Sun, Li-Xiu Liang, Qin-Li Song, Ming-Xin Zhu, Xing-Quan Front Microbiol Microbiology Toxoplasma gondii is an obligate intracellular protozoan parasite, which has a worldwide distribution and can infect a large number of warm-blooded animals and humans. T. gondii must colonize and proliferate inside the host cells in order to maintain its own survival by securing essential nutrients for the development of the newly generated tachyzoites. The type II fatty acid biosynthesis pathway (FASII) in the apicoplast is essential for the growth and survival of T. gondii. We investigated whether deletion of genes in the FASII pathway influences the in vitro growth and in vivo virulence of T. gondii. We focused on beta-hydroxyacyl-acyl carrier protein dehydratase (FabZ) and oxidoreductase, short chain dehydrogenase/reductase family proteins ODSCI and ODSCII. We constructed T. gondii strains deficient in FabZ, ODSCI, and ODSCII using CRISPR-Cas9 gene editing technology. The results of immunofluorescence assay, plaque assay, proliferation assay and egress assay showed that in RHΔFabZ strain the apicoplast was partly lost and the growth ability of the parasite in vitro was significantly inhibited, while for RHΔODSCI and RHΔODSCII mutant strains no similar changes were detected. RHΔFabZ exhibited reduced virulence for mice compared with RHΔODSCI and RHΔODSCII, as shown by the improved survival rate. Deletion of FabZ in the PRU strain significantly decreased the brain cyst burden in mice compared with PRUΔODSCI and PRUΔODSCII. Collectively, these findings suggest that FabZ contributes to the growth and virulence of T. gondii, while ODSCI and ODSCII do not contribute to these traits. Frontiers Media S.A. 2021-08-31 /pmc/articles/PMC8438308/ /pubmed/34531837 http://dx.doi.org/10.3389/fmicb.2021.703059 Text en Copyright © 2021 Xu, Elsheikha, Liu, Zhang, Sun, Liang, Song and Zhu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Xu, Xiao-Pei
Elsheikha, Hany M.
Liu, Wen-Ge
Zhang, Zhi-Wei
Sun, Li-Xiu
Liang, Qin-Li
Song, Ming-Xin
Zhu, Xing-Quan
The Role of Type II Fatty Acid Synthesis Enzymes FabZ, ODSCI, and ODSCII in the Pathogenesis of Toxoplasma gondii Infection
title The Role of Type II Fatty Acid Synthesis Enzymes FabZ, ODSCI, and ODSCII in the Pathogenesis of Toxoplasma gondii Infection
title_full The Role of Type II Fatty Acid Synthesis Enzymes FabZ, ODSCI, and ODSCII in the Pathogenesis of Toxoplasma gondii Infection
title_fullStr The Role of Type II Fatty Acid Synthesis Enzymes FabZ, ODSCI, and ODSCII in the Pathogenesis of Toxoplasma gondii Infection
title_full_unstemmed The Role of Type II Fatty Acid Synthesis Enzymes FabZ, ODSCI, and ODSCII in the Pathogenesis of Toxoplasma gondii Infection
title_short The Role of Type II Fatty Acid Synthesis Enzymes FabZ, ODSCI, and ODSCII in the Pathogenesis of Toxoplasma gondii Infection
title_sort role of type ii fatty acid synthesis enzymes fabz, odsci, and odscii in the pathogenesis of toxoplasma gondii infection
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438308/
https://www.ncbi.nlm.nih.gov/pubmed/34531837
http://dx.doi.org/10.3389/fmicb.2021.703059
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