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...

Descripción completa

Guardado en:
Detalles Bibliográficos
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:
R
Q
Acceso en línea:https://doaj.org/article/da1fde26a8c943f3b0cd78d7331bc63a
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:da1fde26a8c943f3b0cd78d7331bc63a
record_format dspace
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
work_keys_str_mv AT justinytoh identificationofpositiveandnegativeregulatorsinthestepwisedevelopmentalprogressiontowardsinfectivityintrypanosomabrucei
AT agathenkouawa identificationofpositiveandnegativeregulatorsinthestepwisedevelopmentalprogressiontowardsinfectivityintrypanosomabrucei
AT saulrojassanchez identificationofpositiveandnegativeregulatorsinthestepwisedevelopmentalprogressiontowardsinfectivityintrypanosomabrucei
AT huafangshi identificationofpositiveandnegativeregulatorsinthestepwisedevelopmentalprogressiontowardsinfectivityintrypanosomabrucei
AT nikolaygkolev identificationofpositiveandnegativeregulatorsinthestepwisedevelopmentalprogressiontowardsinfectivityintrypanosomabrucei
AT christiantschudi identificationofpositiveandnegativeregulatorsinthestepwisedevelopmentalprogressiontowardsinfectivityintrypanosomabrucei
_version_ 1718385479984873472