Role of 6-phosphogluconate dehydrogenase enzyme 1 in growth and virulence of Toxoplasma gondii and development of attenuated live vaccine.
Journal
Microbial biotechnology
ISSN: 1751-7915
Titre abrégé: Microb Biotechnol
Pays: United States
ID NLM: 101316335
Informations de publication
Date de publication:
Oct 2023
Oct 2023
Historique:
revised:
21
07
2023
received:
06
10
2022
accepted:
24
07
2023
pubmed:
9
8
2023
medline:
9
8
2023
entrez:
9
8
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37556171
doi: 10.1111/1751-7915.14324
pmc: PMC10527188
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1957-1970Subventions
Organisme : Guangdong Major Project of Basic and Applied Basic Research
ID : 2020B0301030007
Organisme : Laboratory for Lingnan Modern Agriculture Project
ID : NT2021007
Organisme : National Natural Science Foundation of China
ID : 32002305
Organisme : Natural Science Foundation of Guangdong Province
ID : 2022A1515011104
Organisme : Science and Technology Program of Guangzhou, China
ID : 202201010500
Informations de copyright
© 2023 The Authors. Microbial Biotechnology published by Applied Microbiology International and John Wiley & Sons Ltd.
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