Identification of positive and negative regulators in the stepwise developmental progression towards infectivity in Trypanosoma brucei

Abstract Trypanosoma brucei is a protozoan parasite that causes important human and livestock diseases in sub-Saharan Africa. By overexpressing a single RNA-binding protein, RBP6, in non-infectious procyclics trypanosomes, we previously recapitulated in vitro the events occurring in the tsetse fly v...

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Autores principales:	Justin Y. Toh, Agathe Nkouawa, Saúl Rojas Sánchez, Huafang Shi, Nikolay G. Kolev, Christian Tschudi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/da1fde26a8c943f3b0cd78d7331bc63a
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spelling	oai:doaj.org-article:da1fde26a8c943f3b0cd78d7331bc63a2021-12-02T15:54:12ZIdentification of positive and negative regulators in the stepwise developmental progression towards infectivity in Trypanosoma brucei10.1038/s41598-021-85225-22045-2322https://doaj.org/article/da1fde26a8c943f3b0cd78d7331bc63a2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85225-2https://doaj.org/toc/2045-2322Abstract Trypanosoma brucei is a protozoan parasite that causes important human and livestock diseases in sub-Saharan Africa. By overexpressing a single RNA-binding protein, RBP6, in non-infectious procyclics trypanosomes, we previously recapitulated in vitro the events occurring in the tsetse fly vector, namely the development of epimastigotes and infectious, quiescent metacyclic parasites. To identify genes involved in this developmental progression, we individually targeted 86 transcripts by RNAi in the RBP6 overexpression cell line and assessed the loss-of-function phenotypes on repositioning the kinetoplast, an organelle that contains the mitochondrial genome, the expression of BARP or brucei alanine rich protein, a marker for epimastigotes, and metacyclic variant surface glycoprotein. This screen identified 22 genes that positively or negatively regulate the stepwise progression towards infectivity at different stages. Two previously uncharacterized putative nucleic acid binding proteins emerged as potent regulators, namely the cold shock domain-containing proteins CSD1 and CSD2. RNA-Seq data from a selected group of cell lines further revealed that the components of gene expression regulatory networks identified in this study affected the abundance of a subset of transcripts in very similar fashion. Finally, our data suggest a considerable overlap between the genes that regulate the formation of stumpy bloodstream form trypanosomes and the genes that govern the development of metacyclic form parasites.Justin Y. TohAgathe NkouawaSaúl Rojas SánchezHuafang ShiNikolay G. KolevChristian TschudiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Justin Y. Toh Agathe Nkouawa Saúl Rojas Sánchez Huafang Shi Nikolay G. Kolev Christian Tschudi Identification of positive and negative regulators in the stepwise developmental progression towards infectivity in Trypanosoma brucei
description	Abstract Trypanosoma brucei is a protozoan parasite that causes important human and livestock diseases in sub-Saharan Africa. By overexpressing a single RNA-binding protein, RBP6, in non-infectious procyclics trypanosomes, we previously recapitulated in vitro the events occurring in the tsetse fly vector, namely the development of epimastigotes and infectious, quiescent metacyclic parasites. To identify genes involved in this developmental progression, we individually targeted 86 transcripts by RNAi in the RBP6 overexpression cell line and assessed the loss-of-function phenotypes on repositioning the kinetoplast, an organelle that contains the mitochondrial genome, the expression of BARP or brucei alanine rich protein, a marker for epimastigotes, and metacyclic variant surface glycoprotein. This screen identified 22 genes that positively or negatively regulate the stepwise progression towards infectivity at different stages. Two previously uncharacterized putative nucleic acid binding proteins emerged as potent regulators, namely the cold shock domain-containing proteins CSD1 and CSD2. RNA-Seq data from a selected group of cell lines further revealed that the components of gene expression regulatory networks identified in this study affected the abundance of a subset of transcripts in very similar fashion. Finally, our data suggest a considerable overlap between the genes that regulate the formation of stumpy bloodstream form trypanosomes and the genes that govern the development of metacyclic form parasites.
format	article
author	Justin Y. Toh Agathe Nkouawa Saúl Rojas Sánchez Huafang Shi Nikolay G. Kolev Christian Tschudi
author_facet	Justin Y. Toh Agathe Nkouawa Saúl Rojas Sánchez Huafang Shi Nikolay G. Kolev Christian Tschudi
author_sort	Justin Y. Toh
title	Identification of positive and negative regulators in the stepwise developmental progression towards infectivity in Trypanosoma brucei
title_short	Identification of positive and negative regulators in the stepwise developmental progression towards infectivity in Trypanosoma brucei
title_full	Identification of positive and negative regulators in the stepwise developmental progression towards infectivity in Trypanosoma brucei
title_fullStr	Identification of positive and negative regulators in the stepwise developmental progression towards infectivity in Trypanosoma brucei
title_full_unstemmed	Identification of positive and negative regulators in the stepwise developmental progression towards infectivity in Trypanosoma brucei
title_sort	identification of positive and negative regulators in the stepwise developmental progression towards infectivity in trypanosoma brucei
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/da1fde26a8c943f3b0cd78d7331bc63a
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Identification of positive and negative regulators in the stepwise developmental progression towards infectivity in Trypanosoma brucei

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