Thiosemicarbazone Copper Chelator BLT-1 Blocks Apicomplexan Parasite Replication by Selective Inhibition of Scavenger Receptor B Type 1 (SR-BI)

Coccidian parasites are obligate intracellular pathogens that affect humans and animals. Apicomplexans are defective in de novo synthesis of cholesterol, which is required for membrane biosynthesis and offspring formation. In consequence, cholesterol has to be scavenged from host cells. It is mainly...

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Autores principales:	Camilo Larrazabal, Sara López-Osorio, Zahady D. Velásquez, Carlos Hermosilla, Anja Taubert, Liliana M. R. Silva
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Toxoplasma gondii</i> <i>Neospora caninum</i> <i>Besnoitia besnoiti</i> <i>Eimeria bovis</i> <i>Eimeria arloingi</i> SR-BI Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/24fecbc6af05416292a514b764d8e898
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spelling	oai:doaj.org-article:24fecbc6af05416292a514b764d8e8982021-11-25T18:25:29ZThiosemicarbazone Copper Chelator BLT-1 Blocks Apicomplexan Parasite Replication by Selective Inhibition of Scavenger Receptor B Type 1 (SR-BI)10.3390/microorganisms91123722076-2607https://doaj.org/article/24fecbc6af05416292a514b764d8e8982021-11-01T00:00:00Zhttps://www.mdpi.com/2076-2607/9/11/2372https://doaj.org/toc/2076-2607Coccidian parasites are obligate intracellular pathogens that affect humans and animals. Apicomplexans are defective in de novo synthesis of cholesterol, which is required for membrane biosynthesis and offspring formation. In consequence, cholesterol has to be scavenged from host cells. It is mainly taken up from extracellular sources via LDL particles; however, little is known on the role of HDL and its receptor SR-BI in this process. Here, we studied effects of the SR-BI-specific blocker BLT-1 on the development of different fast (<i>Toxoplasma gondii</i>, <i>Neospora caninum</i>, <i>Besnoitia besnoiti</i>) and slow (<i>Eimeria bovis</i> and <i>Eimeria arloingi)</i> replicating coccidian species. Overall, development of all these parasites was significantly inhibited by BLT-1 treatment indicating a common SR-BI-related key mechanism in the replication process. However, SR-BI gene transcription was not affected by <i>T. gondii, N. caninum</i> and <i>B. besnoiti</i> infections. Interestingly, BLT-1 treatment of infective stages reduced invasive capacities of all fast replicating parasites paralleled by a sustained increase in cytoplasmic Ca<sup>++</sup> levels. Moreover, BLT1-mediated blockage of SR-BI led to enhanced host cell lipid droplet abundance and neutral lipid content, thereby confirming the importance of this receptor in general lipid metabolism. Finally, the current data suggest a conserved role of SR-BI for successful coccidian infections.Camilo LarrazabalSara López-OsorioZahady D. VelásquezCarlos HermosillaAnja TaubertLiliana M. R. SilvaMDPI AGarticle<i>Toxoplasma gondii</i><i>Neospora caninum</i><i>Besnoitia besnoiti</i><i>Eimeria bovis</i><i>Eimeria arloingi</i>SR-BIBiology (General)QH301-705.5ENMicroorganisms, Vol 9, Iss 2372, p 2372 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Toxoplasma gondii</i> <i>Neospora caninum</i> <i>Besnoitia besnoiti</i> <i>Eimeria bovis</i> <i>Eimeria arloingi</i> SR-BI Biology (General) QH301-705.5
spellingShingle	<i>Toxoplasma gondii</i> <i>Neospora caninum</i> <i>Besnoitia besnoiti</i> <i>Eimeria bovis</i> <i>Eimeria arloingi</i> SR-BI Biology (General) QH301-705.5 Camilo Larrazabal Sara López-Osorio Zahady D. Velásquez Carlos Hermosilla Anja Taubert Liliana M. R. Silva Thiosemicarbazone Copper Chelator BLT-1 Blocks Apicomplexan Parasite Replication by Selective Inhibition of Scavenger Receptor B Type 1 (SR-BI)
description	Coccidian parasites are obligate intracellular pathogens that affect humans and animals. Apicomplexans are defective in de novo synthesis of cholesterol, which is required for membrane biosynthesis and offspring formation. In consequence, cholesterol has to be scavenged from host cells. It is mainly taken up from extracellular sources via LDL particles; however, little is known on the role of HDL and its receptor SR-BI in this process. Here, we studied effects of the SR-BI-specific blocker BLT-1 on the development of different fast (<i>Toxoplasma gondii</i>, <i>Neospora caninum</i>, <i>Besnoitia besnoiti</i>) and slow (<i>Eimeria bovis</i> and <i>Eimeria arloingi)</i> replicating coccidian species. Overall, development of all these parasites was significantly inhibited by BLT-1 treatment indicating a common SR-BI-related key mechanism in the replication process. However, SR-BI gene transcription was not affected by <i>T. gondii, N. caninum</i> and <i>B. besnoiti</i> infections. Interestingly, BLT-1 treatment of infective stages reduced invasive capacities of all fast replicating parasites paralleled by a sustained increase in cytoplasmic Ca<sup>++</sup> levels. Moreover, BLT1-mediated blockage of SR-BI led to enhanced host cell lipid droplet abundance and neutral lipid content, thereby confirming the importance of this receptor in general lipid metabolism. Finally, the current data suggest a conserved role of SR-BI for successful coccidian infections.
format	article
author	Camilo Larrazabal Sara López-Osorio Zahady D. Velásquez Carlos Hermosilla Anja Taubert Liliana M. R. Silva
author_facet	Camilo Larrazabal Sara López-Osorio Zahady D. Velásquez Carlos Hermosilla Anja Taubert Liliana M. R. Silva
author_sort	Camilo Larrazabal
title	Thiosemicarbazone Copper Chelator BLT-1 Blocks Apicomplexan Parasite Replication by Selective Inhibition of Scavenger Receptor B Type 1 (SR-BI)
title_short	Thiosemicarbazone Copper Chelator BLT-1 Blocks Apicomplexan Parasite Replication by Selective Inhibition of Scavenger Receptor B Type 1 (SR-BI)
title_full	Thiosemicarbazone Copper Chelator BLT-1 Blocks Apicomplexan Parasite Replication by Selective Inhibition of Scavenger Receptor B Type 1 (SR-BI)
title_fullStr	Thiosemicarbazone Copper Chelator BLT-1 Blocks Apicomplexan Parasite Replication by Selective Inhibition of Scavenger Receptor B Type 1 (SR-BI)
title_full_unstemmed	Thiosemicarbazone Copper Chelator BLT-1 Blocks Apicomplexan Parasite Replication by Selective Inhibition of Scavenger Receptor B Type 1 (SR-BI)
title_sort	thiosemicarbazone copper chelator blt-1 blocks apicomplexan parasite replication by selective inhibition of scavenger receptor b type 1 (sr-bi)
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/24fecbc6af05416292a514b764d8e898
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Thiosemicarbazone Copper Chelator BLT-1 Blocks Apicomplexan Parasite Replication by Selective Inhibition of Scavenger Receptor B Type 1 (SR-BI)

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