Key roles of amylopectin synthesis and degradation enzymes in the establishment and reactivation of chronic toxoplasmosis
Abstract Toxoplasma gondii (T. gondii) is an obligate intracellular parasite with a wide range of hosts, including humans and many warm-blooded animals. The parasite exists in two interconvertible forms, namely tachyzoites and bradyzoites in intermediate hosts that are responsible for acute and chro...
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| Format: | Article |
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BMC
2023-06-01
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| Series: | Animal Diseases |
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| Online Access: | https://doi.org/10.1186/s44149-023-00083-x |
| _version_ | 1797806752223199232 |
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| author | Pu Chen Congcong Lyu Yidan Wang Ming Pan Xingyu Lin Bang Shen |
| author_facet | Pu Chen Congcong Lyu Yidan Wang Ming Pan Xingyu Lin Bang Shen |
| author_sort | Pu Chen |
| collection | DOAJ |
| description | Abstract Toxoplasma gondii (T. gondii) is an obligate intracellular parasite with a wide range of hosts, including humans and many warm-blooded animals. The parasite exists in two interconvertible forms, namely tachyzoites and bradyzoites in intermediate hosts that are responsible for acute and chronic infections respectively. Mature bradyzoites accumulate large amounts of amylopectin granules but their roles have not been fully characterized. In this study, the predicted key enzymes involved in amylopectin synthesis (UDP-sugar pyrophospharylase, USP) and degradation (alpha-glucan water dikinase, GWD) of ME49 strain were individually knocked out, and then bradyzoite-related phenotyping experiments in vitro and in vivo were performed to dissect their roles during parasite growth and development. Deletion of the usp or gwd gene in the type II strain ME49 reduced the replication rates of tachyzoites in vitro and parasite virulence in vivo, suggesting that amylopectin metabolism is important for optimal tachyzoite growth. Interestingly, the Δusp mutant grew slightly faster than the parental strain under stress conditions that induced bradyzoite transition, which was likely due to the decreased efficiency of bradyzoite formation of the Δusp mutant. Although the Δgwd mutant could convert to bradyzoite robustly in vitro, it was significantly impaired in establishing chronic infection in vivo. Both the Δusp and Δgwd mutants showed a dramatic reduction in the reactivation of chronic infection in an in vitro model. Together, these results suggest that USP and GWD, which are involved in amylopectin synthesis and degradation have important roles in tachyzoite growth, as well as in the formation and reactivation of bradyzoites in T. gondii. |
| first_indexed | 2024-03-13T06:12:04Z |
| format | Article |
| id | doaj.art-047c7fc5c1404d74948da0f47a06be11 |
| institution | Directory Open Access Journal |
| issn | 2731-0442 |
| language | English |
| last_indexed | 2024-03-13T06:12:04Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Animal Diseases |
| spelling | doaj.art-047c7fc5c1404d74948da0f47a06be112023-06-11T11:09:46ZengBMCAnimal Diseases2731-04422023-06-013111110.1186/s44149-023-00083-xKey roles of amylopectin synthesis and degradation enzymes in the establishment and reactivation of chronic toxoplasmosisPu Chen0Congcong Lyu1Yidan Wang2Ming Pan3Xingyu Lin4Bang Shen5State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural UniversityState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural UniversityState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural UniversityState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural UniversityState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural UniversityState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural UniversityAbstract Toxoplasma gondii (T. gondii) is an obligate intracellular parasite with a wide range of hosts, including humans and many warm-blooded animals. The parasite exists in two interconvertible forms, namely tachyzoites and bradyzoites in intermediate hosts that are responsible for acute and chronic infections respectively. Mature bradyzoites accumulate large amounts of amylopectin granules but their roles have not been fully characterized. In this study, the predicted key enzymes involved in amylopectin synthesis (UDP-sugar pyrophospharylase, USP) and degradation (alpha-glucan water dikinase, GWD) of ME49 strain were individually knocked out, and then bradyzoite-related phenotyping experiments in vitro and in vivo were performed to dissect their roles during parasite growth and development. Deletion of the usp or gwd gene in the type II strain ME49 reduced the replication rates of tachyzoites in vitro and parasite virulence in vivo, suggesting that amylopectin metabolism is important for optimal tachyzoite growth. Interestingly, the Δusp mutant grew slightly faster than the parental strain under stress conditions that induced bradyzoite transition, which was likely due to the decreased efficiency of bradyzoite formation of the Δusp mutant. Although the Δgwd mutant could convert to bradyzoite robustly in vitro, it was significantly impaired in establishing chronic infection in vivo. Both the Δusp and Δgwd mutants showed a dramatic reduction in the reactivation of chronic infection in an in vitro model. Together, these results suggest that USP and GWD, which are involved in amylopectin synthesis and degradation have important roles in tachyzoite growth, as well as in the formation and reactivation of bradyzoites in T. gondii.https://doi.org/10.1186/s44149-023-00083-xToxoplasma gondiiAmylopectin metabolismBradyzoitesReactivationChronic infection |
| spellingShingle | Pu Chen Congcong Lyu Yidan Wang Ming Pan Xingyu Lin Bang Shen Key roles of amylopectin synthesis and degradation enzymes in the establishment and reactivation of chronic toxoplasmosis Animal Diseases Toxoplasma gondii Amylopectin metabolism Bradyzoites Reactivation Chronic infection |
| title | Key roles of amylopectin synthesis and degradation enzymes in the establishment and reactivation of chronic toxoplasmosis |
| title_full | Key roles of amylopectin synthesis and degradation enzymes in the establishment and reactivation of chronic toxoplasmosis |
| title_fullStr | Key roles of amylopectin synthesis and degradation enzymes in the establishment and reactivation of chronic toxoplasmosis |
| title_full_unstemmed | Key roles of amylopectin synthesis and degradation enzymes in the establishment and reactivation of chronic toxoplasmosis |
| title_short | Key roles of amylopectin synthesis and degradation enzymes in the establishment and reactivation of chronic toxoplasmosis |
| title_sort | key roles of amylopectin synthesis and degradation enzymes in the establishment and reactivation of chronic toxoplasmosis |
| topic | Toxoplasma gondii Amylopectin metabolism Bradyzoites Reactivation Chronic infection |
| url | https://doi.org/10.1186/s44149-023-00083-x |
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