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Starch Branching Enzyme 1 Is Important for Amylopectin Synthesis and Cyst Reactivation in Toxoplasma gondii

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 bra...

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Autores principales: Yang, Jing, He, Zhengming, Chen, Chengjie, Zhao, Junlong, Fang, Rui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9241709/
https://www.ncbi.nlm.nih.gov/pubmed/35446124
http://dx.doi.org/10.1128/spectrum.01891-21
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author Yang, Jing
He, Zhengming
Chen, Chengjie
Zhao, Junlong
Fang, Rui
author_facet Yang, Jing
He, Zhengming
Chen, Chengjie
Zhao, Junlong
Fang, Rui
author_sort Yang, Jing
collection PubMed
description 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.
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spelling pubmed-92417092022-06-30 Starch Branching Enzyme 1 Is Important for Amylopectin Synthesis and Cyst Reactivation in Toxoplasma gondii Yang, Jing He, Zhengming Chen, Chengjie Zhao, Junlong Fang, Rui Microbiol Spectr Research Article 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. American Society for Microbiology 2022-04-21 /pmc/articles/PMC9241709/ /pubmed/35446124 http://dx.doi.org/10.1128/spectrum.01891-21 Text en Copyright © 2022 Yang et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Yang, Jing
He, Zhengming
Chen, Chengjie
Zhao, Junlong
Fang, Rui
Starch Branching Enzyme 1 Is Important for Amylopectin Synthesis and Cyst Reactivation in Toxoplasma gondii
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 Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9241709/
https://www.ncbi.nlm.nih.gov/pubmed/35446124
http://dx.doi.org/10.1128/spectrum.01891-21
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