Starch Branching Enzyme 1 Is Important for Amylopectin Synthesis and Cyst Reactivation in Toxoplasma gondii
ABSTRACT Toxoplasma gondii (T. gondii) bradyzoites facilitate chronic infections that evade host immune response. Furthermore, reactivation in immunocompromised individuals causes severe toxoplasmosis. The presence of abundant granules containing the branched starch amylopectin is major characterist...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-06-01
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| Series: | Microbiology Spectrum |
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| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.01891-21 |
| _version_ | 1818255516237824000 |
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| author | Jing Yang Zhengming He Chengjie Chen Junlong Zhao Rui Fang |
| author_facet | Jing Yang Zhengming He Chengjie Chen Junlong Zhao Rui Fang |
| author_sort | Jing Yang |
| collection | DOAJ |
| description | ABSTRACT Toxoplasma gondii (T. gondii) bradyzoites facilitate chronic infections that evade host immune response. Furthermore, reactivation in immunocompromised individuals causes severe toxoplasmosis. The presence of abundant granules containing the branched starch amylopectin is major characteristic of bradyzoites that is nearly absent from tachyzoites that drive acute disease. T. gondii genome encodes to potential Starch branching enzyme 1 (SBE1) that creates branching during amylopectin biosynthesis. However, the physiological function of the amylopectin in T. gondii remains unclear. In this study, we generated a SBE1 knockout parasites and revealed that deletion of SBE1 caused amylopectin synthesis defects while having no significant impact on the growth of tachyzoites under normal culture conditions in vitro as well as virulence and brain cyst formation. Nevertheless, SBE1 knockout decreased the influx of exogenous glucose and reduced tachyzoites proliferation in nutrition-deficient conditions. Deletion of SBE1 together with the α-amylase (α-AMY), responsible for starch digestion, abolished amylopectin production and attenuated virulence while restoring brain cyst formation. In addition, cysts with defective amylopectin metabolism showed abnormal morphology and were avirulent to mice. In conclusion, SBE1 is essential for the synthesis of amylopectin, which serves as energy storage during the development and reactivation of bradyzoites. IMPORTANCE Toxoplasmosis has become a global, serious public health problem due to the extensiveness of the host. There are great differences in the energy metabolism in the different stages of infection. The most typical difference is the abundant accumulation of amylopectin granules in bradyzoites, which is almost absent in tachyzoites. Until now, the physiological functions of amylopectin have not been clearly elucidated. We focused on starch branching enzyme 1 (SBE1) in the synthesis pathway to reveal the exact physiological significance of amylopectin. Our study clarified the role of SBE1 in the synthesis pathway and amylopectin in tachyzoites and bradyzoites, and demonstrated that amylopectin, as an important carbon source, was critical to parasites growth under an unfavorable environment and the reactivation of bradyzoites to tachyzoites. The findings obtained from our study provides a new avenue for the development of Toxoplasma vaccines and anti-chronic toxoplasmosis drugs. |
| first_indexed | 2024-12-12T17:13:06Z |
| format | Article |
| id | doaj.art-0ac8d1952afe44149bec1a1fd8ba99ad |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-12-12T17:13:06Z |
| publishDate | 2022-06-01 |
| publisher | American Society for Microbiology |
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| series | Microbiology Spectrum |
| spelling | doaj.art-0ac8d1952afe44149bec1a1fd8ba99ad2022-12-22T00:17:50ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972022-06-0110310.1128/spectrum.01891-21Starch Branching Enzyme 1 Is Important for Amylopectin Synthesis and Cyst Reactivation in Toxoplasma gondiiJing Yang0Zhengming He1Chengjie Chen2Junlong Zhao3Rui Fang4State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, ChinaState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, ChinaState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, ChinaState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, ChinaState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, ChinaABSTRACT Toxoplasma gondii (T. gondii) bradyzoites facilitate chronic infections that evade host immune response. Furthermore, reactivation in immunocompromised individuals causes severe toxoplasmosis. The presence of abundant granules containing the branched starch amylopectin is major characteristic of bradyzoites that is nearly absent from tachyzoites that drive acute disease. T. gondii genome encodes to potential Starch branching enzyme 1 (SBE1) that creates branching during amylopectin biosynthesis. However, the physiological function of the amylopectin in T. gondii remains unclear. In this study, we generated a SBE1 knockout parasites and revealed that deletion of SBE1 caused amylopectin synthesis defects while having no significant impact on the growth of tachyzoites under normal culture conditions in vitro as well as virulence and brain cyst formation. Nevertheless, SBE1 knockout decreased the influx of exogenous glucose and reduced tachyzoites proliferation in nutrition-deficient conditions. Deletion of SBE1 together with the α-amylase (α-AMY), responsible for starch digestion, abolished amylopectin production and attenuated virulence while restoring brain cyst formation. In addition, cysts with defective amylopectin metabolism showed abnormal morphology and were avirulent to mice. In conclusion, SBE1 is essential for the synthesis of amylopectin, which serves as energy storage during the development and reactivation of bradyzoites. IMPORTANCE Toxoplasmosis has become a global, serious public health problem due to the extensiveness of the host. There are great differences in the energy metabolism in the different stages of infection. The most typical difference is the abundant accumulation of amylopectin granules in bradyzoites, which is almost absent in tachyzoites. Until now, the physiological functions of amylopectin have not been clearly elucidated. We focused on starch branching enzyme 1 (SBE1) in the synthesis pathway to reveal the exact physiological significance of amylopectin. Our study clarified the role of SBE1 in the synthesis pathway and amylopectin in tachyzoites and bradyzoites, and demonstrated that amylopectin, as an important carbon source, was critical to parasites growth under an unfavorable environment and the reactivation of bradyzoites to tachyzoites. The findings obtained from our study provides a new avenue for the development of Toxoplasma vaccines and anti-chronic toxoplasmosis drugs.https://journals.asm.org/doi/10.1128/spectrum.01891-21Toxoplasma gondiiamylopectin synthesisstarch branching enzymebradyzoitesreactivation |
| spellingShingle | Jing Yang Zhengming He Chengjie Chen Junlong Zhao Rui Fang Starch Branching Enzyme 1 Is Important for Amylopectin Synthesis and Cyst Reactivation in Toxoplasma gondii Microbiology Spectrum Toxoplasma gondii amylopectin synthesis starch branching enzyme bradyzoites reactivation |
| title | Starch Branching Enzyme 1 Is Important for Amylopectin Synthesis and Cyst Reactivation in Toxoplasma gondii |
| title_full | Starch Branching Enzyme 1 Is Important for Amylopectin Synthesis and Cyst Reactivation in Toxoplasma gondii |
| title_fullStr | Starch Branching Enzyme 1 Is Important for Amylopectin Synthesis and Cyst Reactivation in Toxoplasma gondii |
| title_full_unstemmed | Starch Branching Enzyme 1 Is Important for Amylopectin Synthesis and Cyst Reactivation in Toxoplasma gondii |
| title_short | Starch Branching Enzyme 1 Is Important for Amylopectin Synthesis and Cyst Reactivation in Toxoplasma gondii |
| title_sort | starch branching enzyme 1 is important for amylopectin synthesis and cyst reactivation in toxoplasma gondii |
| topic | Toxoplasma gondii amylopectin synthesis starch branching enzyme bradyzoites reactivation |
| url | https://journals.asm.org/doi/10.1128/spectrum.01891-21 |
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