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Genetic basis for phenotypic differences between different Toxoplasma gondii type I strains

BACKGROUND: Toxoplasma gondii has a largely clonal population in North America and Europe, with types I, II and III clonal lineages accounting for the majority of strains isolated from patients. RH, a particular type I strain, is most frequently used to characterize Toxoplasma biology. However, comp...

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Autores principales: Yang, Ninghan, Farrell, Andrew, Niedelman, Wendy, Melo, Mariane, Lu, Diana, Julien, Lindsay, Marth, Gabor T, Gubbels, Marc-Jan, Saeij, Jeroen PJ
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3710486/
https://www.ncbi.nlm.nih.gov/pubmed/23837824
http://dx.doi.org/10.1186/1471-2164-14-467
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author Yang, Ninghan
Farrell, Andrew
Niedelman, Wendy
Melo, Mariane
Lu, Diana
Julien, Lindsay
Marth, Gabor T
Gubbels, Marc-Jan
Saeij, Jeroen PJ
author_facet Yang, Ninghan
Farrell, Andrew
Niedelman, Wendy
Melo, Mariane
Lu, Diana
Julien, Lindsay
Marth, Gabor T
Gubbels, Marc-Jan
Saeij, Jeroen PJ
author_sort Yang, Ninghan
collection PubMed
description BACKGROUND: Toxoplasma gondii has a largely clonal population in North America and Europe, with types I, II and III clonal lineages accounting for the majority of strains isolated from patients. RH, a particular type I strain, is most frequently used to characterize Toxoplasma biology. However, compared to other type I strains, RH has unique characteristics such as faster growth, increased extracellular survival rate and inability to form orally infectious cysts. Thus, to identify candidate genes that could account for these parasite phenotypic differences, we determined genetic differences and differential parasite gene expression between RH and another type I strain, GT1. Moreover, as differences in host cell modulation could affect Toxoplasma replication in the host, we determined differentially modulated host processes among the type I strains through host transcriptional profiling. RESULTS: Through whole genome sequencing, we identified 1,394 single nucleotide polymorphisms (SNPs) and insertions/deletions (indels) between RH and GT1. These SNPs/indels together with parasite gene expression differences between RH and GT1 were used to identify candidate genes that could account for type I phenotypic differences. A polymorphism in dense granule protein, GRA2, determined RH and GT1 differences in the evasion of the interferon gamma response. In addition, host transcriptional profiling identified that genes regulated by NF-ĸB, such as interleukin (IL)-12p40, were differentially modulated by the different type I strains. We subsequently showed that this difference in NF-ĸB activation was due to polymorphisms in GRA15. Furthermore, we observed that RH, but not other type I strains, recruited phosphorylated IĸBα (a component of the NF-ĸB complex) to the parasitophorous vacuole membrane and this recruitment of p- IĸBα was partially dependent on GRA2. CONCLUSIONS: We identified candidate parasite genes that could be responsible for phenotypic variation among the type I strains through comparative genomics and transcriptomics. We also identified differentially modulated host pathways among the type I strains, and these can serve as a guideline for future studies in examining the phenotypic differences among type I strains.
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spelling pubmed-37104862013-07-14 Genetic basis for phenotypic differences between different Toxoplasma gondii type I strains Yang, Ninghan Farrell, Andrew Niedelman, Wendy Melo, Mariane Lu, Diana Julien, Lindsay Marth, Gabor T Gubbels, Marc-Jan Saeij, Jeroen PJ BMC Genomics Research Article BACKGROUND: Toxoplasma gondii has a largely clonal population in North America and Europe, with types I, II and III clonal lineages accounting for the majority of strains isolated from patients. RH, a particular type I strain, is most frequently used to characterize Toxoplasma biology. However, compared to other type I strains, RH has unique characteristics such as faster growth, increased extracellular survival rate and inability to form orally infectious cysts. Thus, to identify candidate genes that could account for these parasite phenotypic differences, we determined genetic differences and differential parasite gene expression between RH and another type I strain, GT1. Moreover, as differences in host cell modulation could affect Toxoplasma replication in the host, we determined differentially modulated host processes among the type I strains through host transcriptional profiling. RESULTS: Through whole genome sequencing, we identified 1,394 single nucleotide polymorphisms (SNPs) and insertions/deletions (indels) between RH and GT1. These SNPs/indels together with parasite gene expression differences between RH and GT1 were used to identify candidate genes that could account for type I phenotypic differences. A polymorphism in dense granule protein, GRA2, determined RH and GT1 differences in the evasion of the interferon gamma response. In addition, host transcriptional profiling identified that genes regulated by NF-ĸB, such as interleukin (IL)-12p40, were differentially modulated by the different type I strains. We subsequently showed that this difference in NF-ĸB activation was due to polymorphisms in GRA15. Furthermore, we observed that RH, but not other type I strains, recruited phosphorylated IĸBα (a component of the NF-ĸB complex) to the parasitophorous vacuole membrane and this recruitment of p- IĸBα was partially dependent on GRA2. CONCLUSIONS: We identified candidate parasite genes that could be responsible for phenotypic variation among the type I strains through comparative genomics and transcriptomics. We also identified differentially modulated host pathways among the type I strains, and these can serve as a guideline for future studies in examining the phenotypic differences among type I strains. BioMed Central 2013-07-10 /pmc/articles/PMC3710486/ /pubmed/23837824 http://dx.doi.org/10.1186/1471-2164-14-467 Text en Copyright © 2013 Yang et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Yang, Ninghan
Farrell, Andrew
Niedelman, Wendy
Melo, Mariane
Lu, Diana
Julien, Lindsay
Marth, Gabor T
Gubbels, Marc-Jan
Saeij, Jeroen PJ
Genetic basis for phenotypic differences between different Toxoplasma gondii type I strains
title Genetic basis for phenotypic differences between different Toxoplasma gondii type I strains
title_full Genetic basis for phenotypic differences between different Toxoplasma gondii type I strains
title_fullStr Genetic basis for phenotypic differences between different Toxoplasma gondii type I strains
title_full_unstemmed Genetic basis for phenotypic differences between different Toxoplasma gondii type I strains
title_short Genetic basis for phenotypic differences between different Toxoplasma gondii type I strains
title_sort genetic basis for phenotypic differences between different toxoplasma gondii type i strains
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3710486/
https://www.ncbi.nlm.nih.gov/pubmed/23837824
http://dx.doi.org/10.1186/1471-2164-14-467
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