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Transcriptome profiles of the protoscoleces of Echinococcus granulosus reveal that excretory-secretory products are essential to metabolic adaptation.

Pan W, Shen Y, Han X, Wang Y, Liu H, Jiang Y, Zhang Y, Wang Y, Xu Y, Cao J - PLoS Negl Trop Dis (2014)

Bottom Line: Eleven ESPs were identified as intracellular enzymes that regulate glycolysis/gluconeogenesis (GL/GN) pathways, while a further 44 antigenic proteins, 25 molecular chaperones and four proteases were highly represented.Many proteins were also found to be significantly enriched in development-related signaling pathways, such as the TGF-β receptor pathways and insulin pathways.This study provides valuable information on the metabolic adaptation of parasites to their hosts that can be used to aid the development of novel intervention targets for hydatid treatment and control.

View Article: PubMed Central - PubMed

Affiliation: National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, People's Republic of China; Key Laboratory of Parasite and Vector Biology, Ministry of Health, Shanghai, People's Republic of China; WHO Collaborating Center for Malaria, Schistosomiasis and Filariasis, Shanghai, People's Republic of China.

ABSTRACT

Background: Cystic hydatid disease (CHD) is caused by the larval stages of the cestode and affects humans and domestic animals worldwide. Protoscoleces (PSCs) are one component of the larval stages that can interact with both definitive and intermediate hosts. Previous genomic and transcriptomic data have provided an overall snapshot of the genomics of the growth and development of this parasite. However, our understanding of how PSCs subvert the immune response of hosts and maintains metabolic adaptation remains unclear. In this study, we used Roche 454 sequencing technology and in silico secretome analysis to explore the transcriptome profiles of the PSCs from E. granulosus and elucidate the potential functions of the excretory-secretory proteins (ESPs) released by the parasite.

Methodology/principal findings: A large number of nonredundant sequences as unigenes were generated (26,514), of which 22,910 (86.4%) were mapped to the newly published E. granulosus genome and 17,705 (66.8%) were distributed within the coding sequence (CDS) regions. Of the 2,280 ESPs predicted from the transcriptome, 138 ESPs were inferred to be involved in the metabolism of carbohydrates, while 124 ESPs were inferred to be involved in the metabolism of protein. Eleven ESPs were identified as intracellular enzymes that regulate glycolysis/gluconeogenesis (GL/GN) pathways, while a further 44 antigenic proteins, 25 molecular chaperones and four proteases were highly represented. Many proteins were also found to be significantly enriched in development-related signaling pathways, such as the TGF-β receptor pathways and insulin pathways.

Conclusions/significance: This study provides valuable information on the metabolic adaptation of parasites to their hosts that can be used to aid the development of novel intervention targets for hydatid treatment and control.

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Related in: MedlinePlus

The transcription profiling of putative ESPs in EgPSCs transcriptome.The 20 most abundant ESPs encoded in the transcriptome are shown. Abbreviations: RP-S27Ae, putative small subunit ribosomal protein S27Ae; GAPDH, glyceraldehydes-3-phosphate dehydrogenase; ndk, nucleoside diphosphate kinase B-like; ATP2B, Ca2+ transporting ATPase plasma membrane; HSP90α, heat shock protein alpha; 26S p42A, 26S proteasome regulatory complex subunit p42A.
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pntd-0003392-g002: The transcription profiling of putative ESPs in EgPSCs transcriptome.The 20 most abundant ESPs encoded in the transcriptome are shown. Abbreviations: RP-S27Ae, putative small subunit ribosomal protein S27Ae; GAPDH, glyceraldehydes-3-phosphate dehydrogenase; ndk, nucleoside diphosphate kinase B-like; ATP2B, Ca2+ transporting ATPase plasma membrane; HSP90α, heat shock protein alpha; 26S p42A, 26S proteasome regulatory complex subunit p42A.

Mentions: In this study, we found that 36 ESP domains were molecular chaperones (Table S5), and identified a further 25 proteins that were present with high levels of abundance (Table 4), including several novel molecules (heat shock proteins, HSP90 and HSP40, universal stress protein [Usp], calreticulin, calcineurin B, GrpE in the HSP60 family and Gp96). HSP90 was the most strongly expressed of all the molecular chaperons (Fig. 2), suggesting it is one of the key molecules in mediating parasite development. This is supported by the fact that nitration of HSP90 is known to induce cell death [73], and HSP90 has been used as a drug target in protozoa intervention [74]. Previous studies have also shown that UspA and Usp8 are associated with stress resistance and growth in bacterial species [75]. ESPs might disrupt the expression of intracellular 70 protein in the host immune cells, while the parasite itself might release HSP70 to prevent damage from those same cells [76]. These molecular chaperone-like proteins may be released to regulate the stress responses that arise in the extremely harsh intestinal environments of definitive hosts (e.g., numerous highly active proteases, variable pH levels).


Transcriptome profiles of the protoscoleces of Echinococcus granulosus reveal that excretory-secretory products are essential to metabolic adaptation.

Pan W, Shen Y, Han X, Wang Y, Liu H, Jiang Y, Zhang Y, Wang Y, Xu Y, Cao J - PLoS Negl Trop Dis (2014)

The transcription profiling of putative ESPs in EgPSCs transcriptome.The 20 most abundant ESPs encoded in the transcriptome are shown. Abbreviations: RP-S27Ae, putative small subunit ribosomal protein S27Ae; GAPDH, glyceraldehydes-3-phosphate dehydrogenase; ndk, nucleoside diphosphate kinase B-like; ATP2B, Ca2+ transporting ATPase plasma membrane; HSP90α, heat shock protein alpha; 26S p42A, 26S proteasome regulatory complex subunit p42A.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4263413&req=5

pntd-0003392-g002: The transcription profiling of putative ESPs in EgPSCs transcriptome.The 20 most abundant ESPs encoded in the transcriptome are shown. Abbreviations: RP-S27Ae, putative small subunit ribosomal protein S27Ae; GAPDH, glyceraldehydes-3-phosphate dehydrogenase; ndk, nucleoside diphosphate kinase B-like; ATP2B, Ca2+ transporting ATPase plasma membrane; HSP90α, heat shock protein alpha; 26S p42A, 26S proteasome regulatory complex subunit p42A.
Mentions: In this study, we found that 36 ESP domains were molecular chaperones (Table S5), and identified a further 25 proteins that were present with high levels of abundance (Table 4), including several novel molecules (heat shock proteins, HSP90 and HSP40, universal stress protein [Usp], calreticulin, calcineurin B, GrpE in the HSP60 family and Gp96). HSP90 was the most strongly expressed of all the molecular chaperons (Fig. 2), suggesting it is one of the key molecules in mediating parasite development. This is supported by the fact that nitration of HSP90 is known to induce cell death [73], and HSP90 has been used as a drug target in protozoa intervention [74]. Previous studies have also shown that UspA and Usp8 are associated with stress resistance and growth in bacterial species [75]. ESPs might disrupt the expression of intracellular 70 protein in the host immune cells, while the parasite itself might release HSP70 to prevent damage from those same cells [76]. These molecular chaperone-like proteins may be released to regulate the stress responses that arise in the extremely harsh intestinal environments of definitive hosts (e.g., numerous highly active proteases, variable pH levels).

Bottom Line: Eleven ESPs were identified as intracellular enzymes that regulate glycolysis/gluconeogenesis (GL/GN) pathways, while a further 44 antigenic proteins, 25 molecular chaperones and four proteases were highly represented.Many proteins were also found to be significantly enriched in development-related signaling pathways, such as the TGF-β receptor pathways and insulin pathways.This study provides valuable information on the metabolic adaptation of parasites to their hosts that can be used to aid the development of novel intervention targets for hydatid treatment and control.

View Article: PubMed Central - PubMed

Affiliation: National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, People's Republic of China; Key Laboratory of Parasite and Vector Biology, Ministry of Health, Shanghai, People's Republic of China; WHO Collaborating Center for Malaria, Schistosomiasis and Filariasis, Shanghai, People's Republic of China.

ABSTRACT

Background: Cystic hydatid disease (CHD) is caused by the larval stages of the cestode and affects humans and domestic animals worldwide. Protoscoleces (PSCs) are one component of the larval stages that can interact with both definitive and intermediate hosts. Previous genomic and transcriptomic data have provided an overall snapshot of the genomics of the growth and development of this parasite. However, our understanding of how PSCs subvert the immune response of hosts and maintains metabolic adaptation remains unclear. In this study, we used Roche 454 sequencing technology and in silico secretome analysis to explore the transcriptome profiles of the PSCs from E. granulosus and elucidate the potential functions of the excretory-secretory proteins (ESPs) released by the parasite.

Methodology/principal findings: A large number of nonredundant sequences as unigenes were generated (26,514), of which 22,910 (86.4%) were mapped to the newly published E. granulosus genome and 17,705 (66.8%) were distributed within the coding sequence (CDS) regions. Of the 2,280 ESPs predicted from the transcriptome, 138 ESPs were inferred to be involved in the metabolism of carbohydrates, while 124 ESPs were inferred to be involved in the metabolism of protein. Eleven ESPs were identified as intracellular enzymes that regulate glycolysis/gluconeogenesis (GL/GN) pathways, while a further 44 antigenic proteins, 25 molecular chaperones and four proteases were highly represented. Many proteins were also found to be significantly enriched in development-related signaling pathways, such as the TGF-β receptor pathways and insulin pathways.

Conclusions/significance: This study provides valuable information on the metabolic adaptation of parasites to their hosts that can be used to aid the development of novel intervention targets for hydatid treatment and control.

Show MeSH
Related in: MedlinePlus