Statistics of completed genome sequencing for several tapeworms.
Abstract
Cestode parasites rely on their host to obtain their nutrients. Elucidation of tapeworm genomes has shown a remarkable reduction in the coding of multiple enzymes, particularly those of anabolic pathways. Previous findings showed that 10–13% of the proteins found in the vesicular fluid of Taenia solium cysticerci are of host origin. Further proteomic characterization allowed identification of 4,259 different proteins including 891 of host origin in the parasite’s protein lysates. One explanation for this high abundance and diversity of host proteins in the parasite lysates is related to the functional exploitation of host proteins by cysticerci. Supporting this concept is the uptake of host haptoglobin and hemoglobin by the parasite, as a way to acquire iron. Surprisingly, internalized host proteins are minimally degraded by the parasite physiological machinery. Additional proteomic analysis demonstrated that these host proteins become part of the organic matrix of calcareous corpuscles; as 60–70% of the protein content are host proteins. In this review, a collection of available genomic and proteomic data for taeniid cestodes is assembled, the subject of the use and processing of host proteins is particularly addressed; a sketchy and unique cell physiological profile starts to emerge for these parasitic organisms.
Keywords
- Taenia solium
- Cestoda
- Genome
- Proteome
- Host proteins
- Calcareous Corpuscles
1. Introduction
Tapeworms are invertebrate metazoans producing zoonotic parasite diseases in animals and humans. These parasites have a worldwide distribution, but they especially affect human populations in developing countries and are considered neglected diseases [1]. Their larvae, known as metacestodes (including forms such as cysticercus in
Tapeworms produce long-term infections, being able to survive within its host for several years [8], maintaining a dynamic and complex host-parasite relationship [9]. Their lifecycles involve two host (intermediate and final) and include several developmental stages: embryo, larvae and adult stage [10] that can lodge in different tissues of their hosts producing diseases with a wide range of clinical presentations [11].
After description of the genomes of four tapeworms in 2013 [12], molecular studies of these organism have entered an integrative era; including approaches involving genomics, transcriptomics and proteomics [13]. These approaches are presented as promising avenues for the discovery of new pathways to improve our understanding of parasite diseases caused by cestodes, in the hope of developing better surveillance, treatment and control guidelines.
This chapter reviews current perspectives in the study of flatworms; special emphasis is placed on the genomics and proteomics of cestodes and taeniid parasites. The conspicuous and abundant presence of host proteins is particularly considered for taeniid larval forms.
2. The Platyhelminth genome
Access to massive sequencing technologies allowed characterization of entire genomes for some of the most relevant flatworms; being the free living
Genome size (Mb) | No. of Genes | Longest scaffold size (Mb) | N50 length (Mb) | N90 length (kb) | GC content (%) | |
---|---|---|---|---|---|---|
122.3 | 12490 | 0.7 | 0.07 | 5.3 | 43 | |
240 | 12890 | 10.5 | 44.8 | 8500 | 43.7 | |
169 | 13,161 | 7.3 | 0.58 | 29.4 | 43.2 | |
168 | 13,323 | 4.2 | 0.34 | 14.3 | 43.1 | |
115 | 10345 | 20.1 | 13.8 | 2900 | 42.2 | |
114.9 | 10231 | 16 | 5.2 | 200 | 42 | |
115 | 11449 | 0.574 | 0.075 | 3.8 | 42 | |
86 | 8756 | 16 | 10.2 | 11.6 | 41 | |
141.1 | 10241 | 2.4 | 0.5 | 82 | 35.9 | |
177 | 15169 | 6.9 | 2.3 | 412.2 | 35.3 |
Other taeniid genomes have been reported outside the International Helminth Genomes Consortium during the past five years:
3. Gene gain/reduction along tapeworm evolution
The genomic data of the first four tapeworm genomes sequenced [12] permitted identification of reduction events for groups of genes such as Wnt, which corroborated some data that suggested the loss of these genes in trematodes [46]. Moreover, other genes as Nek kinases, peroxisomal genes and ParaHox members, as well as neuropeptides and G-protein coupled receptors (GPCRs) [15].
The loss of approximately 10 Hox gene families in tapeworms during their evolutionary pathway apparently affected the morphology of those organisms, i.e., the lack of eye-cups and gut [12]; Hox genes such as pax3/7, gbx, hbn and rax are mainly involved in neuronal development or eye development [47, 48, 49, 50], as well as ParaHox genes in the formation of the digestive tract [51]. Another type of proteins absent in cestodes are those related to germ cells such as piwi, tudor and Vasa, although the latter have been found possible orthologues in the PL10 family [12].
Tapeworms have developed a specialized detoxification system that includes a single cytochrome p450 gene [12, 52], as well as a redox homeostatic system based on thioredoxin glutathione reductase and the expansion of glutathione S-transferases [53, 54, 55]. In addition, there was an expansion of some very specific protein families such as non-canonical heat shock proteins, with
Our current knowledge on cestode’s and taeniid’s genomes is still limited but the speed of genomic data acquisition can advance significantly in this new era. We envisage a better understanding of these host–parasite interactions, at a molecular/evolutionary level that can help us unravel events that have permitted the adaptations of these platyhelminths to the host environment.
4. Metabolic adaptations of tapeworms
A great impact of having available complete tapeworm genomes is the characterization of the metabolic pathways in these organisms. Now we know that taeniid tapeworms cannot synthesize fatty acids and cholesterol de novo [25, 60]. For example, KEGG analysis for fatty acid biosynthesis in
The synthesis of pyrimidines is also absent for taeniids [65], indicating that they acquire pyrimidines from their hosts. The biosynthesis of purines shows a similar landscape [15]. Parasitic flatworms are considered auxotrophic for eight of the nine amino acids that are essential for humans (Phe, His, Lys, Leu, Met, Thr, Trp, and Val). Cestodes have a limited ability to synthesize amino acids, as an example, serine and proline are absent in
5. Taeniid larval tissues contain large amounts of host proteins
The presence of host proteins in the tissues of the cystic larval forms of taeniids has been known for a long time [66, 67, 68, 69, 70]. It has been proposed that the mechanism for the uptake of these proteins is fluid pinocytosis in the cysticerci of
Recent quantitative estimates indicated that host proteins might represent 11–13% of the protein content in the vesicular fluid of
6. Utilization of host proteins by cysticerci; iron chaperons and IgG
A known trait of parasitism is the use of the host as a provider of resources; sugars, amino acids, nucleosides, vitamins, coenzymes and/or microelements are good examples of resources that a parasite can acquire from its host. However, considering the abundance and diversity of host proteins present in the tissues of taeniid larvae, a pertinent question would be: are these parasites benefited by the accumulation of host proteins, beyond simply serving as a source of amino acids or as osmotic regulators? We have explored a couple of prospects: the use of host iron chaperones for the management of the parasite’s iron necessities, as well as the use of host immunoglobulins as a source of amino acids [70, 71, 74].
Iron is an essential element for virtually all living organisms. Pathogens have evolved mechanisms to uptake iron from their hosts. Usually, iron is uptaken from plasma proteins: hemoglobin (heme prosthetic group) or haptoglobin-hemoglobin complexes, hemopexin (heme prosthetic group), transferrin or lactoferrin (iron), ferritin (iron), etc. In fact, the constant battle between host and pathogens for this element is well-studied [75, 76]. Hepcidin, the hormone that control iron levels in mammals, was first discovered as an antimicrobial peptide [76, 77]. In this light, it is expected that cestodes would acquire iron from their host, however, the mechanism remains elusive. Some evidence have suggested that hemoglobin or the haptoglobin-hemoglobin complexes could serve as an iron source for the cysts [78]. To support this notion, we have documented the immunolocalization of haptoglobin, hemoglobin, hepcidin and ferritin in the cyst; immunoblotting using crude larval extracts confirmed the finding [73]. We also showed that haptoglobin-hemoglobin complexes were detected in crude larval extracts in their expected molecular weight, indicating that those complexes are only marginally degraded. In fact, free haptoglobin purified from cysts protein lysates has been shown to retain their hemoglobin binding activity, suggesting that the cyst are acquiring iron from those sources. However, future studies are needed to understand how the uptake is performed (is there a specific receptor?), how the heme prosthetic group or iron is removed from those complexes? and which parasite proteins are performing those roles.
Another aspect related to the host’s protein uptake by tapeworm’s larvae, is the utilization of these proteins as a source of amino acids. Internalization of IgG has been traced using a metabolically labeled (Leu-3H) IgG produced
7. The calcareous corpuscles as a final deposit for host proteins
The tracking of metabolically radiolabeled IgG demonstrated that cysticerci do not significantly use these proteins as a major source of amino acids [71]. A possibility was that these proteins could end in the calcareous corpuscles (CC), that are known as a waste of toxic metabolites and other materials. These CC are microscopic calcifications occurring in the lumen of protonephridial canals, resulting after accretion of mineral salts (calcium carbonate and calcium phosphate) on an organic matrix composed by polysaccharides and other macromolecules [79, 80]. The CC are involved in the removal of toxic solutes and regulation of mineral trafficking [81]. Formation of CC has been proposed as a mechanism for protecting cysticerci from calcification [79]. The CC represent about 10% of the dry weight of total larval tissue [82]. It has been estimated that in aged
Searching for host proteins in the organic matrix of CC from
8. Conclusions
Genomic and proteomic information on flatworms and particularly on cestode parasites is growing rapidly during the last decade, allowing new approaches to a number of questions.
Taeniid metacestodes uptake large amounts of host proteins, some of which may be used to meet physiological needs of these parasites.
Host proteins appear to be marginally degraded; it’s importance as a source of amino acids appears to be negligible.
Proteomic analyses of the organic matrix of the calcareous corpuscles evidenced that a majority of proteins in the organic matrix are of host origin, suggesting that these proteins are sent to the CC as a final destination.
A consequence of the incremental uptake of host proteins during the lifetime of cysts that terminate being part of the organic matrix of calcareous corpuscles, would be a parallel increment in amount of calcareous corpuscles. Accumulation of corpuscles in larval tissue might represent a biological timer that limits the life span of cysticerci in the host.
Acknowledgments
This report was supported in part by grants A1-5-11306 (CONACYT) and [IN 205820] PAPIIT-UNAM.
Conflict of interest
The authors declare that there are no conflict of interest associated with the manuscript.
References
- 1.
Webb C, Cabada MM. Intestinal cestodes. Current Opinion in Infectious Diseases 2017;30(5):504-510. DOI: 10.1097/QCO.0b013e3282ef579e - 2.
Eckert J, Deplazes P. Biological, Epidemiological, and Clinical Aspects of Echinococcosis, a Zoonosis of Increasing Concern. Clinical Microbiology Reviews. 2004;17(1):107-135. DOI: 10.1128/cmr.17.1.107-135.2004 - 3.
Gripper LB, Welburn SC. Neurocysticercosis infection and disease–A review. Acta Tropica. 2016; 66:218-224. DOI: 10.1016/j.actatropica.2016.11.015Abba - 4.
Abba K, Ramaratnam S, Ranganathan LN. Anthelmintics for people with neurocysticercosis. Cochrane Database of Systematic Reviews 2010;17;2010(3):CD000215. DOI: 10.1002/14651858.CD000215.pub3 - 5.
O’Neal SE, Flecker RH. Hospitalization frequency and charges for neurocysticercosis, Emerging Infectious Diseases. 2015;21(6):969-976. DOI:10.3201/eid2106.141324 - 6.
Brunetti E, Kern P, Vuitton DA. Expert consensus for the diagnosis and treatment of cystic and alveolar echinococcosis in humans. Acta Tropica. 2010;114(1):1-16. DOI: 10.1016/j.actatropica.2009.11.001 - 7.
Garcia HH, Moro PL, Schantz PM. Zoonotic helminth infections of humans: echinococcosis, cysticercosis and fascioliasis. Current Opinion in Infectious Diseases. 2007;20(5):489-494. DOI: 10.1097/QCO.0b013e3282a95e39 - 8.
Olson PD, Littlewood DTJ, Bray RA, Mariaux J. Interrelationships and evolution of the tapeworms (Platyhelminthes: Cestoda). Molecular Phylogenetics and Evolution. 2001;19(3):443-467. DOI: 10.1006/mpev.2001.0930 - 9.
Egger B. Making Heads or Tails of Tapeworms. Trends in Parasitology. 2016;32(7):511-512. DOI: 10.1016/j.pt.2016.04.003. DOI: 10.1016/j.pt.2016.04.003 - 10.
Sulima A, Savijoki K, Bien J, Näreaho A, Salamatin R, Conn DB, et al. Comparative proteomic analysis of Hymenolepis diminuta cysticercoid and adult stages. Frontiers in Microbiology. 2018;15;8:2672. DOI:10.3389/fmicb.2017.02672 - 11.
Craig P, Ito A. Intestinal cestodes. Current Opinion in Infectious Diseases. 2007;20(5):524-532. DOI: 10.1097/QCO.0b013e3282ef579e - 12.
Tsai IJ, Zarowiecki M, Holroyd N, Garciarrubio A, Sanchez-Flores A, Brooks KL, et al. The genomes of four tapeworm species reveal adaptations to parasitism. Nature. 2013;496(7443):57-63. DOI: 10.1038/nature12031 - 13.
Marzano V, Mancinelli L, Bracaglia G, Del Chierico F, Vernocchi P, Di Girolamo F, et al. “Omic” investigations of protozoa and worms for a deeper understanding of the human gut “parasitome.” PLoS Neglected Tropical Diseases. 2017;11(11):e0005916. DOI: 10.1371/journal.pntd.0005916 - 14.
Robb SMC, Ross E, Alvarado AS. SmedGD: The Schmidtea mediterranea genome database. Nucleic Acids Researcher. 2008;36(SUPPL. 1):D599-D606. DOI:10.1093/nar/gkm684 - 15.
Helminth I, Consortium G. Comparative genomics of the major parasitic worms. Nature Genetics. 2019;51(1):163-174. DOI: 10.1038/s41588-018-0262-1 - 16.
Zheng H, Zhang W, Zhang L, Zhang Z, Li J, Lu G, et al. The genome of the hydatid tapeworm Echinococcus granulosus . Nature. 2013;45(10):1168-1175. DOI:10.1038/ng.2757 - 17.
Grohme MA, Schloissnig S, Rozanski A, Pippel M, Young GR, Winkler S, et al. The genome of S. mediterranea and the evolution of cellular core mechanisms. Nature Publishing Group. 2018;554(7690):56-61. DOI: 10.1038/nature25473 - 18.
Rozanski A, Moon HK, Brandl H, Martín-Durán JM, Grohme MA, Hüttner K, et al. PlanMine 3.0 - improvements to a mineable resource of flatworm biology and biodiversity. Nucleic Acids Research. 2019;47(D1):D812–D820. DOI:10.1093/nar/gky1070 - 19.
Luo F, Yin M, Mo X, Sun C, Wu Q , Zhu B, et al. An improved genome assembly of the fluke Schistosoma japonicum . PLoS Neglected Tropical Diseases. 2019;13(8):e0007612. DOI: 10.1371/journal.pntd.0007612 - 20.
Zhou Y, Zheng H, Chen Y, Zhang L, Wang K, Guo J, et al. The Schistosoma japonicum genome reveals features of host-parasite interplay. Nature. 2009; 460(7253):345-351. DOI: 10.1038/nature08140 - 21.
Young ND, Jex AR, Li B, Liu S, Yang L, Xiong Z, et al. Whole-genome sequence of Schistosoma haematobium . Nature Genetics. 2012;44(2):221-225. DOI:10.1038/ng.1065 - 22.
Stroehlein AJ, Korhonen PK, Chong TM, Lim YL, Chan KG, Webster B, et al. High-quality Schistosoma haematobium genome achieved by single-molecule and long-range sequencing. Gigascience. 2019;8(9):1-12. DOI:10.1093/gigascience/giz108 - 23.
Berriman M, Haas BJ, Loverde PT, Wilson RA, Dillon GP, Cerqueira GC, et al. The genome of the blood fluke Schistosoma mansoni . Nature. 2009;460(7253):352-358. DOI: 10.1038/nature08160 - 24.
Protasio A V., Tsai IJ, Babbage A, Nichol S, Hunt M, Aslett MA, et al. A systematically improved high quality genome and transcriptome of the human blood fluke Schistosoma mansoni . PLoS Neglected Tropical Diseases. 2012;6(1):1455. DOI: 10.1371/journal.pntd.0001455 - 25.
Wang X, Chen W, Huang Y, Sun J, Men J, Liu H, et al. The draft genome of the carcinogenic human liver fluke Clonorchis sinensis . Genome Biology. 2011;12(10):R107. DOI: 10.1186/gb-2011-12-10-r107 - 26.
Huang Y, Chen W, Wang X, Liu H, Chen Y, Guo L, et al. The Carcinogenic Liver Fluke, Clonorchis sinensis : New Assembly, Reannotation and Analysis of the Genome and Characterization of Tissue Transcriptomes. PLoS One. 2013;8(1):e54732. DOI: 10.1371/journal.pone.0054732 - 27.
Wasik K, Gurtowski J, Zhou X, Ramos OM, Delás MJ, Battistoni G, et al. Genome and transcriptome of the regeneration-competent flatworm, Macrostomum lignano. PNAS. 2015;112(40):12462-12467. DOI:10.1073/pnas.1516718112 - 28.
Wudarski J, Simanov D, Ustyantsev K, De Mulder K, Grelling M, Grudniewska M, et al. Efficient transgenesis and annotated genome sequence of the regenerative flatworm model Macrostomum lignano . Nature Communications 2017;8(1):1-12. DOI: 10.1038/s41467-017-02214-8 - 29.
Hahn C, Fromm B, Bachmann L. Comparative Genomics of Flatworms (Platyhelminthes) Reveals Shared Genomic Features of Ecto- and Endoparastic Neodermata. Genome Biology and Evolution. 2014;6(5):1105-1117. DOI:10.1093/gbe/evu078 - 30.
Young ND, Nagarajan N, Lin SJ, Korhonen PK, Jex AR, Hall RS, et al. The Opisthorchis viverrini genome provides insights into life in the bile duct. Nature Communications. 2014;5(13):1-11. DOI:10.1038/ncomms5378 - 31.
Wang S, Wang S, Luo Y, Xiao L, Luo X, Gao S, et al. Comparative genomics reveals adaptive evolution of Asian tapeworm in switching to a new intermediate host. Nature Communications. 2016;7(1):1-12. DOI:10.1038/ncomms12845 - 32.
Maldonado LL, Assis J, Araújo FMG, Salim ACM, Macchiaroli N, Cucher M, et al. The Echinococcus canadensis ( G7 ) genome : a key knowledge of parasitic platyhelminth human diseases. BMC Genomics. 2017;1-23. DOI:10.1186/s12864-017-3574-0 - 33.
McNulty SN, Tort JF, Rinaldi G, Fischer K, Rosa BA, Smircich P, et al. Genomes of Fasciola hepatica from the Americas Reveal Colonization with Neorickettsia Endobacteria Related to the Agents of Potomac Horse and Human Sennetsu Fevers. PLOS Genetics. 2017;13(1):e1006537. DOI:10.1371/journal.pgen.1006537 - 34.
Li W, Liu B, Yang Y, Ren Y, Wang S, Liu C, et al. The genome of tapeworm Taenia multiceps sheds light on understanding parasitic mechanism and control of coenurosis disease. DNA Research. 2018;25(June):499-510. DOI:10.1093/dnares/dsy020 - 35.
Maldonado LL, Arrabal JP, Rosenzvit MC, Kamenetzky L. Revisiting the Phylogenetic History of Helminths Through Genomics , the Case of the New Echinococcus oligarthrus Genome. Frontiers in Genetics. 2019;10:708. DOI:10.3389/fgene.2019.00708 - 36.
Nowak RM, Jastr JP, Kuśmirek W, Sałamatin R, Rydzanicz M, Sobczyk-kopcioł A, et al. Assembly and annotation of the model tapeworm Hymenolepis diminuta . Scientific Data. 2019;3;6(1):302. DOI: 10.1038/s41597-019-0311-3 - 37.
Ershov NI, Mordvinov VA, Prokhortchouk EB, Pakharukova MY, Gunbin K V., Ustyantsev K, et al. New insights from Opisthorchis felineus genome: Update on genomics of the epidemiologically important liver flukes. BMC Genomics 2019;20(1):1-22. DOI: 10.1186/s12864-019-5752-8 - 38.
Oey H, Zakrzewski M, Narain K, Devi KR, Agatsuma T, Nawaratna S, et al. Whole-genome sequence of the oriental lung fluke Paragonimus westermani . Gigascience. 2018; 8(1):1-8. DOI: 10.1093/gigascience/giy146 - 39.
Oey H, Zakrzewski M, Gravermann K, Young ND, Korhonen PK, Gobert GN, et al. Whole-genome sequence of the bovine blood fluke Schistosoma bovis supports interspecific hybridization with S .Haematobium . PLoS Pathogens. 2019;15(1):e1007513–e1007513. DOI: 10.1371/journal.ppat.1007513 - 40.
Howe KL, Bolt BJ, Shafie M, Kersey P, Berriman M. WormBase ParaSite − a comprehensive resource for helminth genomics. Molecular and Biochemical Parasitology. 2017;215:2-10. DOI: 10.1016/j.molbiopara.2016.11.005 - 41.
Howe KL, Bolt BJ, Cain S, Chan J, Chen WJ, Davis P, et al. WormBase 2016: expanding to enable helminth genomic research. Nucleic Acids Reseacher. 2016;44(D1):D774–D780. DOI: 10.1093/nar/gkv1217 - 42.
Thomas SH, Wagner RD, Arakaki AK, Skolnick J, Kirby JR, Shimkets LJ, et al. The Mosaic Genome of Anaeromyxobacter dehalogenans Strain 2CP-C Suggests an Aerobic Common Ancestor to the Delta-Proteobacteria. PLoS One 2008;3(5):e2103. DOI: 10.1371/journal.pone.0002103 - 43.
Vinogradov AE. Genome size and GC-percent in vertebrates as determined by flow cytometry: The triangular relationship. Cytometry. 1998;31(2):100-109. DOI:10.1002/(sici)1097-0320(19980201)31:2<100::aid-cyto5>3.0.co;2-q - 44.
Zhao Z, Zhang F. Sequence context analysis in the mouse genome: Single nucleotide polymorphisms and CpG island sequences. Genomics.;87:68-74. DOI: 10.1016/j.ygeno.2005.09.012 - 45.
Piovesan A, Pelleri MC, Antonaros F, Strippoli P, Caracausi M, Vitale L. On the length, weight and GC content of the human genome. BMC Research Notes. 2019;12(1):106. DOI:10.1186/s13104-019-4137-z - 46.
Riddiford N, Olson PD. Wnt gene loss in flatworms. Development Genes and Evolution. 2011;221(4):187-197. DOI: 10.1007/s00427-011-0370-8 - 47.
Philippidou P, Dasen JS. Hox Genes: Choreographers in Neural Development, Architects of Circuit Organization. Neuron. 2013;2;80(1):12-34. DOI:10.1016/j.neuron.2013.09.020 - 48.
Mathers PH, Grinberg A, Mahon KA, Jamrich M. The Rx homeobox gene is essential for vertebrate eye development. Nature. 1997;387(6633):603-607. DOI:10.1038/42475 - 49.
Castro LFC, Rasmussen SLK, Holland PWH, Holland ND, Holland LZ. A Gbx homeobox gene in amphioxus: Insights into ancestry of the ANTP class and evolution of the midbrain/hindbrain boundary. Developmental Biology. 2006;1;295(1):40-51. DOI: 10.1016/j.ydbio.2006.03.003 - 50.
Walldorf U, Kiewe A, Wickert M, Ronshaugen M, McGinnis W. Homeobrain, a novel paired-like homeobox gene is expressed in the Drosophila brain. Mechanisms of Development. 2000;96(1):141-144. DOI: 10.1016/s0925-4773(00)00380-4 - 51.
Brooke NM, Garcia-Fernàndez J, Holland PWH. The ParaHox gene cluster is an evolutionary sister of the Hox gene cluster. Nature. 1998;15];392(6679):920-2. DOI: 10.1038/31933 - 52.
Pakharukova MY, Vavilin VA, Sripa B, Laha T, Brindley PJ, Mordvinov VA. Functional Analysis of the Unique Cytochrome P450 of the Liver Fluke Opisthorchis felineus. PLoS Neglected Tropical Diseases. 2015;9(12): e0004258. DOI: doi: 10.1371/journal.pntd.0004258 - 53.
Salinas G, Selkirk ME, Chalar C, Maizels RM, Fernández C. Linked thioredoxin-glutathione systems in platyhelminths. Trends in Parasitology. 2004, 20(7):340-346. DOI: 10.1016/j.pt.2004.05.002 - 54.
Cvilink V, Lamka J, Skálová L. Xenobiotic metabolizing enzymes and metabolism of anthelminthics in helminthes. Drug Metabolism Reviews. 2009; 41(1):8-26. DOI: 10.1080/03602530802602880 - 55.
Harispe L, García G, Arbildi P, Pascovich L, Chalar C, Zaha A, et al. Biochemical analysis of a recombinant glutathione transferase from the cestode Echinococcus granulosus . Acta Tropica. 2010;114(1):31-36. DOI:10.1016/j.actatropica.2009.12.003 - 56.
Huang X, Xu J, Wang Y, Guo C, Chen L, Gu X, et al. GP50 as a promising early diagnostic antigen for Taenia multiceps infection in goats by indirect ELISA. Parasites and Vectors. 2016;9(1):618. DOI: 10.1186/s13071-016-1915-5 - 57.
Muro C, Gomez-Puerta LA, Flecker RH, Gamboa R, Barreto PV, Dorny P, et al. Porcine cysticercosis: Possible cross-reactivity of Taenia hydatigena to GP50 antigen in the enzyme-linked immunoelectrotransfer blot assay. The American Journal of Tropical Medicine and Hygiene. 2017;97(6):1830-1832. DOI: 10.4269/ajtmh.17-0378 - 58.
Hancock K, Pattabh S, Greene RM, Yushak ML, Williams F,et al. Characterization and cloning of GP50, a Taenia solium antigen diagnostic for cysticercosis. Molecular and Biochemical Parasitology. 2004;133(1):115-124. DOI:10.1016/j.molbiopara.2003.10.001 - 59.
Garcia HH, O’Neal SE, Noh J, Handali S, Gilman RH, Gonzalez AE, et al. Laboratory diagnosis of neurocysticercosis ( Taenia solium ). Journal of Clinical Microbiology. 2018;56(9). DOI: 10.1128/JCM.00424-18 - 60.
Frayha GJ. Comparative metabolism of acetate in the taeniid tapeworms Echinococcus granulosus ,E. multilocularis andTaenia hydatigena . Comparative Biochemistry and Physiology Part B: Comparative Biochemistry Comp Biochem Physiol - Part B Biochem. Elsevier. 1971;39(1):167-170. DOI: 10.1016/0305-0491(71)90264-1 - 61.
Kanehisa M, Goto S. KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Research, 2000; 1;28(1):27-30. DOI: 10.1093/nar/28.1.27 - 62.
Kanehisa M. Toward understanding the origin and evolution of cellular organisms. Protein Science. 2019;28(11):1947-1951. DOI: 10.1002/pro.3715 - 63.
Illescas O, Carrero JC, Bobes RJ, Flisser A, Rosas G, Laclette JP. Molecular characterization, functional expression, tissue localization and protective potential of a Taenia solium fatty acid-binding protein. Molecular and Biochemical Parasitology. 2012 Dec 1;186(2):117-125. DOI:10.1016/j.molbiopara.2012.10.002 - 64.
Pearce EJ, Huang SCC. The metabolic control of schistosome egg production. Cell Microbiology. 2015;17(6):796-801. DOI: 10.1111/cmi.12444 - 65.
Heath RL. Biosynthesis de novo of purines and pyrimidines in Mesocestoides (Cestoda) I. International Journal of Parasitology. 1970;56(1):98-102 - 66.
Hustead ST, Williams JF. Permeability studies on taeniid metacestodes. II. Antibody mediated effects on membrane permeability in larvae of Taenia taeniaeformis andTaenia crassiceps . Journal of Parasitology. 1977;63(2):322-326 - 67.
Machnicka B, Grzybowski J. Host serum proteins in Taenia saginata metacestode fluid. Veterinary Parasitology. 1986;19(1-2):47-54. DOI:10.1016/0304-4017(86)90031-2 - 68.
Hayunga EG, Sumner MP, Letonja T. Evidence for selective incorporation of host immunoglobulin by strobilocerci of Taenia taeniaeformis . Journal of Parasitology. 1989;75(4):638-642 - 69.
Ambrosio J, Landa A, Merchant MT, Laclette JP. Protein uptake by cysticerci of Taenia crassiceps . Archives of medical research. 1994; 25(3):325-330 - 70.
Aldridge JR, Jennette MA, Kuhn RE. Uptake and Secretion of Host Proteins by Taenia crassiceps Metacestodes. Journal of Parasitology. 2006;1;92(5):1101-2. DOI: 10.1645/GE-835R.1 - 71.
Flores-Bautista J, Navarrete-Perea J, Fragoso G, Flisser A, Soberón X, Laclette JP. Fate of uptaken host proteins in Taenia solium andTaenia crassiceps cysticerci. Biosciences Report. 2018;6;38(4). DOI: 10.1042/BSR20180636 - 72.
Damian RT. Presidential Address: The Exploitation of Host Immune Responses by Parasites. Journal of Parasitology. 1987;73(1):1. DOI:10.1017/s0031182097002357 - 73.
Navarreta-Pera J, Isasa M, Paulo JA, Corral-corral R, Flores-bautista J, Herna B, Gygi SP, et al. Quantitative multiplexed proteomics of Taenia solium cysts obtained from the skeletal muscle and central nervous system of pigs. 2017; 25;11(9):e0005962. DOI: 10.1371/journal.pntd.0005962 - 74.
Navarrete-Perea J, Moguel B, Mendoza-Hernández G, Fragoso G, Sciutto E, Bobes RJ, et al. Identification and quantification of host proteins in the vesicular fluid of porcine Taenia solium cysticerci. Experimental Parasitology. 2014 Aug;143(1):11-17. DOI: 10.1016/j.exppara.2014.04.011 - 75.
Kronstad JW, Caza M. Shared and distinct mechanisms of iron acquisition by bacterial and fungal pathogens of humans. Frontiers in Cellular and Infection Microbiology. 2013; 19;3:80. DOI: 10.3389/fcimb.2013.00080 - 76.
Barton JC, Acton RT. Hepcidin, iron, and bacterial infection. In: Vitamins and Hormones. Academic Press Inc. 2019;110:223-242. DOI:10.1016/bs.vh.2019.01.011 - 77.
Yiannikourides A, Latunde-Dada G. A Short Review of Iron Metabolism and Pathophysiology of Iron Disorders. Medicines. 2019;6(3):85. DOI:10.3390/medicines6030085 - 78.
Navarrete-Perea J, Toledano-Magaña Y, De La Torre P, Sciutto E, Bobes RJ, Soberón X, et al. Role of porcine serum haptoglobin in the host-parasite relationship of Taenia solium cysticercosis. Molecular and Biochemical Parasitology. 2016;1;207(2):61-7. DOI: 10.1016/j.molbiopara.2016.05.010 - 79.
Vargas-Parada L, Merchant MT, Willms K, Laclette JP. Formation of calcareous corpuscles in the lumen of excretory canals of Taenia solium cysticerci. Parasitology Research. 1999;85(2):88-92. DOI: 10.1007/s004360050514 - 80.
von Brand T, Nylen MU, Martin GN, Churchwell FK, Stites E. Cestode calcareous corpuscles: Phosphate relationships, crystallization patterns, and variations in size and shape. Experimental Parasitology. 1969;25(C):291-310. DOI: 10.1016/0014-4894(69)90075-7 - 81.
McCullough JS, Fairweather I. The structure, composition, formation and possible functions of calcareous corpuscles in Trilocularia acanthiaevulgaris Olsson 1867 (Cestoda, Tetraphyllidea). Parasitology Researcher. 1987;74(2):175-182. DOI: 10.1007/BF00536030 - 82.
Chung YB, Kong Y, Cho SY, Yang HJ. Purification and localization of a 10 kDa calcareous corpuscle binding protein of Spirometra mansoni plerocercoid. 2 Parasitology Research. 2003;235-237. DOI: 10.1007/s00436-002-0694-4