Comparative transcriptome analysis of geographically distinct virulent and attenuated Babesia bovis strains reveals similar gene expression changes through attenuation

Background: Loss of virulence is a phenotypic adaptation commonly seen in prokaryotic and eukaryotic pathogens. This mechanism is not well studied, especially in organisms with multiple host and life cycle stages such as Babesia, a tick-transmitted hemoparasite of humans and animals. B. bovis, which...

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Autores principales: Pedroni, Monica J., Sondgeroth, Kerry S., Gallego-Lopez, Gina M., Echaide, Ignacio Eduardo, Lau, Audrey OT
Formato: info:ar-repo/semantics/artículo
Lenguaje:Inglés
Publicado: 2018
Materias:
Acceso en línea:https://bmcgenomics.biomedcentral.com/articles/10.1186/1471-2164-14-763
http://hdl.handle.net/20.500.12123/3367
https://doi.org/10.1186/1471-2164-14-763
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author Pedroni, Monica J.
Sondgeroth, Kerry S.
Gallego-Lopez, Gina M.
Echaide, Ignacio Eduardo
Lau, Audrey OT
author_browse Echaide, Ignacio Eduardo
Gallego-Lopez, Gina M.
Lau, Audrey OT
Pedroni, Monica J.
Sondgeroth, Kerry S.
author_facet Pedroni, Monica J.
Sondgeroth, Kerry S.
Gallego-Lopez, Gina M.
Echaide, Ignacio Eduardo
Lau, Audrey OT
author_sort Pedroni, Monica J.
collection INTA Digital
description Background: Loss of virulence is a phenotypic adaptation commonly seen in prokaryotic and eukaryotic pathogens. This mechanism is not well studied, especially in organisms with multiple host and life cycle stages such as Babesia, a tick-transmitted hemoparasite of humans and animals. B. bovis, which infects cattle, has naturally occurring virulent strains that can be reliably attenuated in vivo. Previous studies suggest the virulence loss mechanism may involve post-genomic modification. We investigated the transcriptome profiles of two geographically distinct B. bovis virulent and attenuated strain pairs to better understand virulence loss and to gain insight into pathogen adaptation strategies. Results: Expression microarray and RNA-sequencing approaches were employed to compare transcriptome profiles of two B. bovis strain pairs, with each pair consisting of a virulent parental and its attenuated derivative strain. Differentially regulated transcripts were identified within each strain pair. These included genes encoding for VESA1, SmORFs, undefined membrane and hypothetical proteins. The majority of individual specific gene transcripts differentially regulated within a strain were not shared between the two strains. There was a disproportionately greater number of ves genes upregulated in the virulent parental strains. When compared with their attenuated derivatives, divergently oriented ves genes were included among the upregulated ves genes in the virulent strains, while none of the upregulated ves genes in the attenuated derivatives were oriented head to head. One gene family whose specific members were consistently and significantly upregulated in expression in both attenuated strains was spherical body protein (SBP) 2 encoding gene where SBP2 truncated copies 7, 9 and 11 transcripts were all upregulated. Conclusions: We conclude that ves heterodimer pair upregulation and overall higher frequency of ves gene expressions in the virulent strains is consistent with the involvement of this gene family in virulence. This is logical given the role of VESA1 proteins in cytoadherence of infected cells to endothelial cells. However, upregulation of some ves genes in the attenuated derivatives suggests that the consequence of upregulation is gene-specific. Furthermore, upregulation of the spherical body protein 2 gene family may play a role in the attenuated phenotype. Exactly how these two gene families may contribute to the loss or gain of virulence is discussed.
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spelling INTA33672018-09-14T16:10:06Z Comparative transcriptome analysis of geographically distinct virulent and attenuated Babesia bovis strains reveals similar gene expression changes through attenuation Pedroni, Monica J. Sondgeroth, Kerry S. Gallego-Lopez, Gina M. Echaide, Ignacio Eduardo Lau, Audrey OT Babesia bovis Genética Vacuna Viva Expresión Génica Secuencia Nucleotídica Genetics Live Vaccines Gene Expression Nucleotide Sequence Vacuna Atenuada Background: Loss of virulence is a phenotypic adaptation commonly seen in prokaryotic and eukaryotic pathogens. This mechanism is not well studied, especially in organisms with multiple host and life cycle stages such as Babesia, a tick-transmitted hemoparasite of humans and animals. B. bovis, which infects cattle, has naturally occurring virulent strains that can be reliably attenuated in vivo. Previous studies suggest the virulence loss mechanism may involve post-genomic modification. We investigated the transcriptome profiles of two geographically distinct B. bovis virulent and attenuated strain pairs to better understand virulence loss and to gain insight into pathogen adaptation strategies. Results: Expression microarray and RNA-sequencing approaches were employed to compare transcriptome profiles of two B. bovis strain pairs, with each pair consisting of a virulent parental and its attenuated derivative strain. Differentially regulated transcripts were identified within each strain pair. These included genes encoding for VESA1, SmORFs, undefined membrane and hypothetical proteins. The majority of individual specific gene transcripts differentially regulated within a strain were not shared between the two strains. There was a disproportionately greater number of ves genes upregulated in the virulent parental strains. When compared with their attenuated derivatives, divergently oriented ves genes were included among the upregulated ves genes in the virulent strains, while none of the upregulated ves genes in the attenuated derivatives were oriented head to head. One gene family whose specific members were consistently and significantly upregulated in expression in both attenuated strains was spherical body protein (SBP) 2 encoding gene where SBP2 truncated copies 7, 9 and 11 transcripts were all upregulated. Conclusions: We conclude that ves heterodimer pair upregulation and overall higher frequency of ves gene expressions in the virulent strains is consistent with the involvement of this gene family in virulence. This is logical given the role of VESA1 proteins in cytoadherence of infected cells to endothelial cells. However, upregulation of some ves genes in the attenuated derivatives suggests that the consequence of upregulation is gene-specific. Furthermore, upregulation of the spherical body protein 2 gene family may play a role in the attenuated phenotype. Exactly how these two gene families may contribute to the loss or gain of virulence is discussed. EEA Rafaela Fil: Pedroni, Monica J. Washington State University. College of Veterinary Medicine. Department of Veterinary Microbiology & Pathology. Program of Genomics; Estados Unidos Fil: Sondgeroth, Kerry S. Washington State University. College of Veterinary Medicine. Department of Veterinary Microbiology & Pathology. Program of Genomics; Estados Unidos Fil: Gallego-Lopez, Gina M. Washington State University. College of Veterinary Medicine. Department of Veterinary Microbiology & Pathology. Program of Genomics; Estados Unidos Fil: Echaide, Ignacio Eduardo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela. Laboratorio de Inmunología y Parasitología; Argentina Fil: Lau, Audrey OT. Washington State University. College of Veterinary Medicine. Department of Veterinary Microbiology & Pathology. Program of Genomics; Estados Unidos. Washington State University. College of Veterinary Medicine. Paul G. Allen School for Global Animal Health; Estados Unidos 2018-09-14T16:08:06Z 2018-09-14T16:08:06Z 2013-11 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion https://bmcgenomics.biomedcentral.com/articles/10.1186/1471-2164-14-763 http://hdl.handle.net/20.500.12123/3367 1471-2164 https://doi.org/10.1186/1471-2164-14-763 eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) application/pdf BMC Genomics 14 : 763 (2013)
spellingShingle Babesia bovis
Genética
Vacuna Viva
Expresión Génica
Secuencia Nucleotídica
Genetics
Live Vaccines
Gene Expression
Nucleotide Sequence
Vacuna Atenuada
Pedroni, Monica J.
Sondgeroth, Kerry S.
Gallego-Lopez, Gina M.
Echaide, Ignacio Eduardo
Lau, Audrey OT
Comparative transcriptome analysis of geographically distinct virulent and attenuated Babesia bovis strains reveals similar gene expression changes through attenuation
title Comparative transcriptome analysis of geographically distinct virulent and attenuated Babesia bovis strains reveals similar gene expression changes through attenuation
title_full Comparative transcriptome analysis of geographically distinct virulent and attenuated Babesia bovis strains reveals similar gene expression changes through attenuation
title_fullStr Comparative transcriptome analysis of geographically distinct virulent and attenuated Babesia bovis strains reveals similar gene expression changes through attenuation
title_full_unstemmed Comparative transcriptome analysis of geographically distinct virulent and attenuated Babesia bovis strains reveals similar gene expression changes through attenuation
title_short Comparative transcriptome analysis of geographically distinct virulent and attenuated Babesia bovis strains reveals similar gene expression changes through attenuation
title_sort comparative transcriptome analysis of geographically distinct virulent and attenuated babesia bovis strains reveals similar gene expression changes through attenuation
topic Babesia bovis
Genética
Vacuna Viva
Expresión Génica
Secuencia Nucleotídica
Genetics
Live Vaccines
Gene Expression
Nucleotide Sequence
Vacuna Atenuada
url https://bmcgenomics.biomedcentral.com/articles/10.1186/1471-2164-14-763
http://hdl.handle.net/20.500.12123/3367
https://doi.org/10.1186/1471-2164-14-763
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