Stage-Specific and Selective Delivery of Caged Azidosugars into the Intracellular Parasite <italic toggle="yes">Toxoplasma gondii</italic> by Using an Esterase-Ester Pair Technique

ABSTRACT Toxoplasma gondii is an obligate intracellular parasite that chronically infects up to a third of the human population. The parasites persist in the form of cysts in the central nervous system and serve as a reservoir for the reactivation of toxoplasmic encephalitis. The cyst wall is known...

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Autores principales:	Tadakimi Tomita, Hua Wang, Peng Wu, Louis M. Weiss
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	chemical biology click chemistry glycobiology intracellular pathogen porcine esterase small molecular delivery Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/31a18a400d9f44cb8d433b77a2b9f679
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spelling	oai:doaj.org-article:31a18a400d9f44cb8d433b77a2b9f6792021-11-15T15:22:20ZStage-Specific and Selective Delivery of Caged Azidosugars into the Intracellular Parasite <italic toggle="yes">Toxoplasma gondii</italic> by Using an Esterase-Ester Pair Technique10.1128/mSphere.00142-192379-5042https://doaj.org/article/31a18a400d9f44cb8d433b77a2b9f6792019-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00142-19https://doaj.org/toc/2379-5042ABSTRACT Toxoplasma gondii is an obligate intracellular parasite that chronically infects up to a third of the human population. The parasites persist in the form of cysts in the central nervous system and serve as a reservoir for the reactivation of toxoplasmic encephalitis. The cyst wall is known to have abundant O-linked N-acetylgalactosamine glycans, but the existing metabolic labeling methods do not allow selective labeling of intracellular parasite glycoproteins without labeling of host glycans. In this study, we have integrated Cu(I)-catalyzed bioorthogonal click chemistry with a specific esterase-ester pair system in order to selectively deliver azidosugars to the intracellular parasites. We demonstrated that α-cyclopropyl modified GalNAz was cleaved by porcine liver esterase produced in the parasites but not in the host cells. Our proof-of-concept study demonstrates the feasibility and potential of this esterase-ester click chemistry approach for the selective delivery of small molecules in a stage-specific manner. IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells. We have devised a method that can deliver caged molecules into an intracellular parasite, Toxoplasma gondii, that express an uncaging enzyme in a stage-specific manner without affecting host cell biology. This system provides a valuable tool for studying many intracellular parasites.Tadakimi TomitaHua WangPeng WuLouis M. WeissAmerican Society for Microbiologyarticlechemical biologyclick chemistryglycobiologyintracellular pathogenporcine esterasesmall molecular deliveryMicrobiologyQR1-502ENmSphere, Vol 4, Iss 3 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	chemical biology click chemistry glycobiology intracellular pathogen porcine esterase small molecular delivery Microbiology QR1-502
spellingShingle	chemical biology click chemistry glycobiology intracellular pathogen porcine esterase small molecular delivery Microbiology QR1-502 Tadakimi Tomita Hua Wang Peng Wu Louis M. Weiss Stage-Specific and Selective Delivery of Caged Azidosugars into the Intracellular Parasite <italic toggle="yes">Toxoplasma gondii</italic> by Using an Esterase-Ester Pair Technique
description	ABSTRACT Toxoplasma gondii is an obligate intracellular parasite that chronically infects up to a third of the human population. The parasites persist in the form of cysts in the central nervous system and serve as a reservoir for the reactivation of toxoplasmic encephalitis. The cyst wall is known to have abundant O-linked N-acetylgalactosamine glycans, but the existing metabolic labeling methods do not allow selective labeling of intracellular parasite glycoproteins without labeling of host glycans. In this study, we have integrated Cu(I)-catalyzed bioorthogonal click chemistry with a specific esterase-ester pair system in order to selectively deliver azidosugars to the intracellular parasites. We demonstrated that α-cyclopropyl modified GalNAz was cleaved by porcine liver esterase produced in the parasites but not in the host cells. Our proof-of-concept study demonstrates the feasibility and potential of this esterase-ester click chemistry approach for the selective delivery of small molecules in a stage-specific manner. IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells. We have devised a method that can deliver caged molecules into an intracellular parasite, Toxoplasma gondii, that express an uncaging enzyme in a stage-specific manner without affecting host cell biology. This system provides a valuable tool for studying many intracellular parasites.
format	article
author	Tadakimi Tomita Hua Wang Peng Wu Louis M. Weiss
author_facet	Tadakimi Tomita Hua Wang Peng Wu Louis M. Weiss
author_sort	Tadakimi Tomita
title	Stage-Specific and Selective Delivery of Caged Azidosugars into the Intracellular Parasite <italic toggle="yes">Toxoplasma gondii</italic> by Using an Esterase-Ester Pair Technique
title_short	Stage-Specific and Selective Delivery of Caged Azidosugars into the Intracellular Parasite <italic toggle="yes">Toxoplasma gondii</italic> by Using an Esterase-Ester Pair Technique
title_full	Stage-Specific and Selective Delivery of Caged Azidosugars into the Intracellular Parasite <italic toggle="yes">Toxoplasma gondii</italic> by Using an Esterase-Ester Pair Technique
title_fullStr	Stage-Specific and Selective Delivery of Caged Azidosugars into the Intracellular Parasite <italic toggle="yes">Toxoplasma gondii</italic> by Using an Esterase-Ester Pair Technique
title_full_unstemmed	Stage-Specific and Selective Delivery of Caged Azidosugars into the Intracellular Parasite <italic toggle="yes">Toxoplasma gondii</italic> by Using an Esterase-Ester Pair Technique
title_sort	stage-specific and selective delivery of caged azidosugars into the intracellular parasite <italic toggle="yes">toxoplasma gondii</italic> by using an esterase-ester pair technique
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/31a18a400d9f44cb8d433b77a2b9f679
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Stage-Specific and Selective Delivery of Caged Azidosugars into the Intracellular Parasite <italic toggle="yes">Toxoplasma gondii</italic> by Using an Esterase-Ester Pair Technique

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