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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.

Show MeSH

Related in: MedlinePlus

Schematic diagram showing the carbohydrate metabolic pathways involved in the ESPs of EgPSCs transcriptome (Reference from Eisenreich W et al. [19] with some modifications).Glycolysis (GL, purple arrows) and gluconeogenesis (GN, grass green arrows); pentose-phosphate pathway (PPP, broken purple arrows); tricarboxylic acid cycle (TCA, blue circle) other catabolic reactions that occur in the mitochondrion and in the cytosol (black arrows). Anabolic reactions leading to amino acids, nucleotides, and lipids are indicated by broken thick black arrows. Metabolites are marked in black. Enzymes identified in our study are marked in red, while other enzymes are marked in blue. Abbreviations: HK, hexokinase; PFK, phosphofructokinase; FBP, fructose bisphosphatase; PK, pyruvate kinase; PDH, pyruvate dehydrogenase complex; PCK, PEP-carboxylase; PPI, phosphohexose isomerase; TPI, triose phosphate isomerase; PGK, phosphoglycerate kinase; GAPDH, glyceraldehydes 3-phosphate dehydrogenase; PC, pyruvate carboxylase; LDH, lactate dehydrogenase; PEPCK, phosphoenol pyruvate carboxykinase; G6PD, glucose-6-phosphate dehydrogenase; ALDOA, fructose-biphosphate aldolase; PGK, phosphoglycerate kinase; PGAM, phosphoglycerate mutase; ENO, enolase; G6Pase, glucose 6-phosphatase; G6PD, glucose-6-phosphate dehydrogenase; 6GPDH, 6-phosphogluconatedehydrogenase. Gln, Glutanine; Asp, aspartic acid; Arg, arginine; Pro, proline; His, histidine; Ala, alanine; Tyr, tyrosine; Cys, cysteine; Ade, adenine; Hyp, hypoxanthine.
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pntd-0003392-g001: Schematic diagram showing the carbohydrate metabolic pathways involved in the ESPs of EgPSCs transcriptome (Reference from Eisenreich W et al. [19] with some modifications).Glycolysis (GL, purple arrows) and gluconeogenesis (GN, grass green arrows); pentose-phosphate pathway (PPP, broken purple arrows); tricarboxylic acid cycle (TCA, blue circle) other catabolic reactions that occur in the mitochondrion and in the cytosol (black arrows). Anabolic reactions leading to amino acids, nucleotides, and lipids are indicated by broken thick black arrows. Metabolites are marked in black. Enzymes identified in our study are marked in red, while other enzymes are marked in blue. Abbreviations: HK, hexokinase; PFK, phosphofructokinase; FBP, fructose bisphosphatase; PK, pyruvate kinase; PDH, pyruvate dehydrogenase complex; PCK, PEP-carboxylase; PPI, phosphohexose isomerase; TPI, triose phosphate isomerase; PGK, phosphoglycerate kinase; GAPDH, glyceraldehydes 3-phosphate dehydrogenase; PC, pyruvate carboxylase; LDH, lactate dehydrogenase; PEPCK, phosphoenol pyruvate carboxykinase; G6PD, glucose-6-phosphate dehydrogenase; ALDOA, fructose-biphosphate aldolase; PGK, phosphoglycerate kinase; PGAM, phosphoglycerate mutase; ENO, enolase; G6Pase, glucose 6-phosphatase; G6PD, glucose-6-phosphate dehydrogenase; 6GPDH, 6-phosphogluconatedehydrogenase. Gln, Glutanine; Asp, aspartic acid; Arg, arginine; Pro, proline; His, histidine; Ala, alanine; Tyr, tyrosine; Cys, cysteine; Ade, adenine; Hyp, hypoxanthine.

Mentions: E. granulosus has evolved an optimal strategy to gain energy and nutrition from its host using ESPs (Fig. 1). Firstly, the parasite can regulate glycolysis (GL). We identified nine enzymes associated with GL, including the rate-limiting enzymes PFK1 and pyruvate kinase. Through GL, non-essential amino acids (e.g., glutamine, aspartic acid, arginine, proline, histidine, alanine, tyrosine and cysteine), fatty acids, adenine and hypoxanthine nucleotides, as well as pyrimidine, could be synthesized to support parasite development and growth. Alternatively, glucose and other carbohydrates could be synthesized via gluconeogenesis (GN) when alternative carbon sources (e.g., glucogenic amino acids, lactate, and glycerol) were available. In addition to the reversible enzymatic GL steps, several reactions are essential in the GN pathway from pyruvate via oxaloacetate to glucose: the reactions catalyzed by pyruvate carboxylase, phosphoenolpyuvate carboxykinase (PEPCK), fructose-1, 6-bisphosphatase, and glucose-6-phosphatase leading to oxaloacetate, phosphoenolpyruvate (PEP), fructose-6-phosphate, and glucose. Finally, tricarboxylic acid (TCA) enzymes, such as aconitate hydratase, succinate dehydrogenase complex, malate dehydrogenase, were identified in the TCA cycle. Other enzymes involved in carbohydrate metabolism are shown in Table 4.


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)

Schematic diagram showing the carbohydrate metabolic pathways involved in the ESPs of EgPSCs transcriptome (Reference from Eisenreich W et al. [19] with some modifications).Glycolysis (GL, purple arrows) and gluconeogenesis (GN, grass green arrows); pentose-phosphate pathway (PPP, broken purple arrows); tricarboxylic acid cycle (TCA, blue circle) other catabolic reactions that occur in the mitochondrion and in the cytosol (black arrows). Anabolic reactions leading to amino acids, nucleotides, and lipids are indicated by broken thick black arrows. Metabolites are marked in black. Enzymes identified in our study are marked in red, while other enzymes are marked in blue. Abbreviations: HK, hexokinase; PFK, phosphofructokinase; FBP, fructose bisphosphatase; PK, pyruvate kinase; PDH, pyruvate dehydrogenase complex; PCK, PEP-carboxylase; PPI, phosphohexose isomerase; TPI, triose phosphate isomerase; PGK, phosphoglycerate kinase; GAPDH, glyceraldehydes 3-phosphate dehydrogenase; PC, pyruvate carboxylase; LDH, lactate dehydrogenase; PEPCK, phosphoenol pyruvate carboxykinase; G6PD, glucose-6-phosphate dehydrogenase; ALDOA, fructose-biphosphate aldolase; PGK, phosphoglycerate kinase; PGAM, phosphoglycerate mutase; ENO, enolase; G6Pase, glucose 6-phosphatase; G6PD, glucose-6-phosphate dehydrogenase; 6GPDH, 6-phosphogluconatedehydrogenase. Gln, Glutanine; Asp, aspartic acid; Arg, arginine; Pro, proline; His, histidine; Ala, alanine; Tyr, tyrosine; Cys, cysteine; Ade, adenine; Hyp, hypoxanthine.
© Copyright Policy
Related In: Results  -  Collection

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

pntd-0003392-g001: Schematic diagram showing the carbohydrate metabolic pathways involved in the ESPs of EgPSCs transcriptome (Reference from Eisenreich W et al. [19] with some modifications).Glycolysis (GL, purple arrows) and gluconeogenesis (GN, grass green arrows); pentose-phosphate pathway (PPP, broken purple arrows); tricarboxylic acid cycle (TCA, blue circle) other catabolic reactions that occur in the mitochondrion and in the cytosol (black arrows). Anabolic reactions leading to amino acids, nucleotides, and lipids are indicated by broken thick black arrows. Metabolites are marked in black. Enzymes identified in our study are marked in red, while other enzymes are marked in blue. Abbreviations: HK, hexokinase; PFK, phosphofructokinase; FBP, fructose bisphosphatase; PK, pyruvate kinase; PDH, pyruvate dehydrogenase complex; PCK, PEP-carboxylase; PPI, phosphohexose isomerase; TPI, triose phosphate isomerase; PGK, phosphoglycerate kinase; GAPDH, glyceraldehydes 3-phosphate dehydrogenase; PC, pyruvate carboxylase; LDH, lactate dehydrogenase; PEPCK, phosphoenol pyruvate carboxykinase; G6PD, glucose-6-phosphate dehydrogenase; ALDOA, fructose-biphosphate aldolase; PGK, phosphoglycerate kinase; PGAM, phosphoglycerate mutase; ENO, enolase; G6Pase, glucose 6-phosphatase; G6PD, glucose-6-phosphate dehydrogenase; 6GPDH, 6-phosphogluconatedehydrogenase. Gln, Glutanine; Asp, aspartic acid; Arg, arginine; Pro, proline; His, histidine; Ala, alanine; Tyr, tyrosine; Cys, cysteine; Ade, adenine; Hyp, hypoxanthine.
Mentions: E. granulosus has evolved an optimal strategy to gain energy and nutrition from its host using ESPs (Fig. 1). Firstly, the parasite can regulate glycolysis (GL). We identified nine enzymes associated with GL, including the rate-limiting enzymes PFK1 and pyruvate kinase. Through GL, non-essential amino acids (e.g., glutamine, aspartic acid, arginine, proline, histidine, alanine, tyrosine and cysteine), fatty acids, adenine and hypoxanthine nucleotides, as well as pyrimidine, could be synthesized to support parasite development and growth. Alternatively, glucose and other carbohydrates could be synthesized via gluconeogenesis (GN) when alternative carbon sources (e.g., glucogenic amino acids, lactate, and glycerol) were available. In addition to the reversible enzymatic GL steps, several reactions are essential in the GN pathway from pyruvate via oxaloacetate to glucose: the reactions catalyzed by pyruvate carboxylase, phosphoenolpyuvate carboxykinase (PEPCK), fructose-1, 6-bisphosphatase, and glucose-6-phosphatase leading to oxaloacetate, phosphoenolpyruvate (PEP), fructose-6-phosphate, and glucose. Finally, tricarboxylic acid (TCA) enzymes, such as aconitate hydratase, succinate dehydrogenase complex, malate dehydrogenase, were identified in the TCA cycle. Other enzymes involved in carbohydrate metabolism are shown in Table 4.

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