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Role of 6‐phosphogluconate dehydrogenase enzyme 1 in growth and virulence of Toxoplasma gondii and development of attenuated live vaccine
Toxoplasma gondii is a ubiquitous pathogen that infects all warm‐blooded animals, including humans, causing substantial socioeconomic and healthcare burdens. However, there is no ideal vaccine for toxoplasmosis. As metabolism is important in the growth and virulence of Toxoplasma, some key pathways...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10527188/ https://www.ncbi.nlm.nih.gov/pubmed/37556171 http://dx.doi.org/10.1111/1751-7915.14324 |
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author | Guo, Qinghong Guo, Xuefang Ji, Nuo Shen, Bang Zhong, Xinhua Xiao, Lihua Feng, Yaoyu Xia, Ningbo |
author_facet | Guo, Qinghong Guo, Xuefang Ji, Nuo Shen, Bang Zhong, Xinhua Xiao, Lihua Feng, Yaoyu Xia, Ningbo |
author_sort | Guo, Qinghong |
collection | PubMed |
description | Toxoplasma gondii is a ubiquitous pathogen that infects all warm‐blooded animals, including humans, causing substantial socioeconomic and healthcare burdens. However, there is no ideal vaccine for toxoplasmosis. As metabolism is important in the growth and virulence of Toxoplasma, some key pathways are promising antiparasitic targets. Here, we identified 6‐phosphogluconate dehydrogenase 1 (Tg6PGDH1) in the oxidative pentose phosphate pathway as a cytoplasmic protein that is dispensable for tachyzoite growth of T. gondii in vitro but critical for virulence and cyst formation in vivo. The depletion of Tg6PGDH1 causes decreased gene transcription involved in signal transduction, transcriptional regulation and virulence. Furthermore, we analysed the protective effect of the ME49Δ6pgdh1 mutant as an attenuated vaccine and found that ME49Δ6pgdh1 immunization stimulated strong protective immunity against lethal challenges and blocked cyst formation caused by reinfection. Furthermore, we showed that ME49Δ6pgdh1 immunization stimulated increased levels of interferon‐gamma, tumour necrosis factor‐alpha and Toxoplasma‐specific IgG antibodies. These data highlight the role of Tg6PGDH1 in the growth and virulence of T. gondii and its potential as a target for the development of a live‐attenuated vaccine. |
format | Online Article Text |
id | pubmed-10527188 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-105271882023-09-28 Role of 6‐phosphogluconate dehydrogenase enzyme 1 in growth and virulence of Toxoplasma gondii and development of attenuated live vaccine Guo, Qinghong Guo, Xuefang Ji, Nuo Shen, Bang Zhong, Xinhua Xiao, Lihua Feng, Yaoyu Xia, Ningbo Microb Biotechnol Research Articles Toxoplasma gondii is a ubiquitous pathogen that infects all warm‐blooded animals, including humans, causing substantial socioeconomic and healthcare burdens. However, there is no ideal vaccine for toxoplasmosis. As metabolism is important in the growth and virulence of Toxoplasma, some key pathways are promising antiparasitic targets. Here, we identified 6‐phosphogluconate dehydrogenase 1 (Tg6PGDH1) in the oxidative pentose phosphate pathway as a cytoplasmic protein that is dispensable for tachyzoite growth of T. gondii in vitro but critical for virulence and cyst formation in vivo. The depletion of Tg6PGDH1 causes decreased gene transcription involved in signal transduction, transcriptional regulation and virulence. Furthermore, we analysed the protective effect of the ME49Δ6pgdh1 mutant as an attenuated vaccine and found that ME49Δ6pgdh1 immunization stimulated strong protective immunity against lethal challenges and blocked cyst formation caused by reinfection. Furthermore, we showed that ME49Δ6pgdh1 immunization stimulated increased levels of interferon‐gamma, tumour necrosis factor‐alpha and Toxoplasma‐specific IgG antibodies. These data highlight the role of Tg6PGDH1 in the growth and virulence of T. gondii and its potential as a target for the development of a live‐attenuated vaccine. John Wiley and Sons Inc. 2023-08-09 /pmc/articles/PMC10527188/ /pubmed/37556171 http://dx.doi.org/10.1111/1751-7915.14324 Text en © 2023 The Authors. Microbial Biotechnology published by Applied Microbiology International and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Research Articles Guo, Qinghong Guo, Xuefang Ji, Nuo Shen, Bang Zhong, Xinhua Xiao, Lihua Feng, Yaoyu Xia, Ningbo Role of 6‐phosphogluconate dehydrogenase enzyme 1 in growth and virulence of Toxoplasma gondii and development of attenuated live vaccine |
title | Role of 6‐phosphogluconate dehydrogenase enzyme 1 in growth and virulence of Toxoplasma gondii and development of attenuated live vaccine |
title_full | Role of 6‐phosphogluconate dehydrogenase enzyme 1 in growth and virulence of Toxoplasma gondii and development of attenuated live vaccine |
title_fullStr | Role of 6‐phosphogluconate dehydrogenase enzyme 1 in growth and virulence of Toxoplasma gondii and development of attenuated live vaccine |
title_full_unstemmed | Role of 6‐phosphogluconate dehydrogenase enzyme 1 in growth and virulence of Toxoplasma gondii and development of attenuated live vaccine |
title_short | Role of 6‐phosphogluconate dehydrogenase enzyme 1 in growth and virulence of Toxoplasma gondii and development of attenuated live vaccine |
title_sort | role of 6‐phosphogluconate dehydrogenase enzyme 1 in growth and virulence of toxoplasma gondii and development of attenuated live vaccine |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10527188/ https://www.ncbi.nlm.nih.gov/pubmed/37556171 http://dx.doi.org/10.1111/1751-7915.14324 |
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