Hostname: page-component-cd9895bd7-gxg78 Total loading time: 0 Render date: 2024-12-19T03:02:37.427Z Has data issue: false hasContentIssue false

The genome of Strongyloides spp. gives insights into protein families with a putative role in nematode parasitism

Published online by Cambridge University Press:  13 September 2016

VICKY L. HUNT*
Affiliation:
School of Biological Sciences, Life Sciences Building, University of Bristol, Bristol BS8 1TQ, UK
ISHENG J. TSAI
Affiliation:
Biodiversity Research Center, Academia Sinica, Taipei 11529, Taiwan
MURRAY E. SELKIRK
Affiliation:
Department of Life Sciences, Department of Life Sciences, Imperial College London, London SW7 2AZ, UK
MARK VINEY
Affiliation:
School of Biological Sciences, Life Sciences Building, University of Bristol, Bristol BS8 1TQ, UK
*
*Corresponding author: School of Biological Sciences, Life Sciences Building, University of Bristol, Bristol BS8 1TQ, UK. E-mail: [email protected]

Summary

Parasitic nematodes are important and abundant parasites adapted to live a parasitic lifestyle, with these adaptations all aimed at facilitating their survival and reproduction in their hosts. The recently sequenced genomes of four Strongyloides species, gastrointestinal parasites of humans and other animals, alongside transcriptomic and proteomic analysis of free-living and parasitic stages of their life cycles have revealed a number of protein families with a putative role in their parasitism. Many of these protein families have also been associated with parasitism in other parasitic nematode species, suggesting that these proteins may play a fundamental role in nematode parasitism more generally. Here, we review key protein families that have a putative role in Strongyloides’ parasitism – acetylcholinesterases, astacins, aspartic proteases, prolyl oligopeptidases, proteinase inhibitors (trypsin inhibitors and cystatins), SCP/TAPS and transthyretin-like proteins – and the evidence for their key, yet diverse, roles in the parasitic lifestyle.

Type
Special Issue Review
Copyright
Copyright © Cambridge University Press 2016 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Albertson, D. G., Nwaorgu, O. C. and Sulston, J. E. (1979). Chromatin diminution and a chromosomal mechanism of sexual differentiation in Strongyloides papillosus . Chromosoma 75, 7587.Google Scholar
Armstrong, S. D., Babayan, S. A., Lhermitte-Vallarino, N., Gray, N., Xia, D., Martin, C., Kumar, S., Taylor, D. W., Blaxter, M. L., Wastling, J. M. and Makepeace, B. L. (2014). Comparative analysis of the secretome from a model filarial nematode (Litomosoides sigmodontis) reveals maximal diversity in gravid female parasites. Molecular & Cellular Proteomics 13, 25272544.CrossRefGoogle Scholar
Arumugam, S., Zhan, B., Abraham, D., Ward, D., Lustigman, S. and Klei, T. R. (2014). Vaccination with recombinant Brugia malayi cystatin proteins alters worm migration, homing and final niche selection following a subcutaneous challenge of Mongolian gerbils (Meriones unguiculatus) with B. malayi infective larvae. Parasites & Vectors 7, 43.Google Scholar
Asojo, O. A. (2011). Structure of a two-CAP-domain protein from the human hookworm parasite Necator americanus . Acta crystallographica., Biological Crystallography 67, 455462.Google Scholar
Asojo, O. A., Goud, G., Dhar, K., Loukas, A., Zhan, B., Deumic, V., Liu, S., Borgstahl, G. E. O. and Hotez, P. J. (2005). X-ray structure of Na-ASP-2, a pathogenesis-related-1 protein from the nematode parasite, Necator americanus, and a vaccine antigen for human hookworm infection. Journal of Molecular Biology 346, 801814.CrossRefGoogle Scholar
Balasubramanian, N., Toubarro, D., Nascimento, G., Ferreira, R. and Simões, N. (2012). Purification, molecular characterization and gene expression analysis of an aspartic protease (Sc-ASP113) from the nematode Steinernema carpocapsae during the parasitic stage. Molecular and Biochemical Parasitology 182, 3744.Google Scholar
Bastos, I. M. D., Grellier, P., Martins, N. F., Cadavid-Restrepo, G., de Souza-Ault, M. R., Augustyns, K., Teixeira, A. R. L., Schrével, J., Maigret, B., da Silveira, J. F. and Santana, J. M. (2005). Molecular, functional and structural properties of the prolyl oligopeptidase of Trypanosoma cruzi (POP Tc80), which is required for parasite entry into mammalian cells. Biochemical Journal 388, 2938.CrossRefGoogle ScholarPubMed
Bastos, I. M. D., Motta, F. N., Grellier, P. and Santana, J. M. (2013). Parasite prolyl oligopeptidases and the challenge of designing chemotherapeuticals for Chagas disease, leishmaniasis and African trypanosomiasis. Current Medicinal Chemistry 20, 31033115.Google Scholar
Bolla, R. I. and Roberts, L. S. (1968). Gametogenesis and chromosomal complement in Strongyloides ratti (Nematoda: Rhabdiasoidea). Journal of Parasitology 54, 849855.Google Scholar
Bond, J. S. and Beynon, R. J. (1995). The astacin family of metalloendopeptidases. Protein Science 4, 12471261.Google Scholar
Borchert, N., Becker-Pauly, C., Wagner, A., Fischer, P., Stöcker, W. and Brattig, N. W. (2007). Identification and characterization of onchoastacin, an astacin-like metalloproteinase from the filaria Onchocerca volvulus . Microbes and Infection 9, 498506.Google Scholar
Brindley, P. J., Gam, A. A., McKerrow, J. H. and Neva, F. A. (1995). Ss40: the zinc endopeptidase secreted by infective larvae of Strongyloides stercoralis . Experimental Parasitology 80, 17.Google Scholar
Brindley, P. J., Kalinna, B. H., Wong, J. Y., Bogitsh, B. J., King, L. T., Smyth, D. J., Verity, C. K., Abbenante, G., Brinkworth, R. I., Fairlie, D. P., Smythe, M. L., Milburn, P. J., Bielefeldt-Ohmann, H., Zheng, Y. and McManus, D. P. (2001). Proteolysis of human hemoglobin by schistosome cathepsin D. Molecular and Biochemical Parasitology 112, 103112.CrossRefGoogle ScholarPubMed
Camargo, A. C., Caldo, H. and Reis, M. L. (1979). Susceptibility of a peptide derived from bradykinin to hydrolysis by brain endo-oligopeptidases and pancreatic proteinases. Journal of Biological Chemistry 254, 53045307.CrossRefGoogle ScholarPubMed
Cantacessi, C. and Gasser, R. B. (2012). SCP/TAPS proteins in helminths – where to from now? Molecular and Cellular Probes 26, 5459.Google Scholar
Cantacessi, C., Campbell, B. E., Visser, A., Geldhof, P., Nolan, M. J., Nisbet, A. J., Matthews, J. B., Loukas, A., Hofmann, A., Otranto, D., Sternberg, P. W. and Gasser, R. B. (2009). A portrait of the “SCP/TAPS” proteins of eukaryotes-developing a framework for fundamental research and biotechnological outcomes. Biotechnology Advances 27, 376388.CrossRefGoogle ScholarPubMed
Cantacessi, C., Gasser, R. B., Strube, C., Schnieder, T., Jex, A. R., Hall, R. S., Campbell, B. E., Young, N. D., Ranganathan, S., Sternberg, P. W. and Mitreva, M. (2011). Deep insights into Dictyocaulus viviparus transcriptomes provides unique prospects for new drug targets and disease intervention. Biotechnology Advances 29, 261271.Google Scholar
Cappello, M., Vlasuk, G. P., Bergum, P. W., Huang, S. and Hotez, P. J. (1995). Ancylostoma caninum anticoagulant peptide: a hookworm-derived inhibitor of human coagulation factor Xa. Proceedings of the National Academy of Sciences of the United States of America 92, 61526156.Google Scholar
Chen, C. K.-M., Chan, N.-L. and Wang, A. H.-J. (2011). The many blades of the β-propeller proteins: conserved but versatile. Trends in Biochemical Sciences 36, 553561.CrossRefGoogle ScholarPubMed
Combes, D., Fedon, Y., Grauso, M., Toutant, J. P. and Arpagaus, M. (2000). Four genes encode acetylcholinesterases in the nematodes Caenorhabditis elegans and Caenorhabditis briggsae. cDNA sequences, genomic structures, mutations and in vivo expression. Journal of Molecular Biology 300, 727742.Google Scholar
Culetto, E., Combes, D., Fedon, Y., Roig, A., Toutant, J. P. and Arpagaus, M. (1999). Structure and promoter activity of the 5’ flanking region of ace-1, the gene encoding acetylcholinesterase of class A in Caenorhabditis elegans . Journal of Molecular Biology 290, 951966.Google Scholar
Culley, F. J., Brown, A., Conroy, D. M., Sabroe, I., Pritchard, D. I. and Williams, T. J. (2000). Eotaxin is specifically cleaved by hookworm metalloproteases preventing its action in vitro and in vivo . Journal of Immunology 165, 64476453.Google Scholar
Culotti, J. G., Von Ehrenstein, G., Culotti, M. R. and Russell, R. L. (1981). A second class of acetylcholinesterase-deficient mutants of the nematode Caenorhabditis elegans . Genetics 97, 281305.Google Scholar
Dainichi, T., Maekawa, Y., Ishii, K., Zhang, T., Nashed, B. F., Sakai, T., Takashima, M. and Himeno, K. (2001). Nippocystatin, a cysteine protease inhibitor from Nippostrongylus brasiliensis, inhibits antigen processing and modulates antigen-specific immune response. Infection and Immunity 69, 73807386.Google Scholar
Darby, M., Schnoeller, C., Vira, A., Culley, F., Bobat, S., Logan, E., Kirstein, F., Wess, J., Cunningham, A. F., Brombacher, F., Selkirk, M. E. and Horsnell, W. G. C. (2015). The M3 Muscarinic receptor is required for optimal adaptive immunity to Helminth and bacterial infection. PLoS Pathogens 11, 115.CrossRefGoogle ScholarPubMed
Dash, C., Kulkarni, A., Dunn, B. and Rao, M. (2003). Aspartic peptidase inhibitors: implications in drug development. Critical Reviews in Biochemistry and Molecular Biology 38, 89119.Google Scholar
Davis, M. W., Birnie, A. J., Chan, A. C., Page, A. P. and Jorgensen, E. M. (2004). A conserved metalloprotease mediates ecdysis in Caenorhabditis elegans . Development 131, 60016008.Google Scholar
Del Valle, A., Jones, B. F., Harrison, L. M., Chadderdon, R. C. and Cappello, M. (2003). Isolation and molecular cloning of a secreted hookworm platelet inhibitor from adult Ancylostoma caninum . Molecular and Biochemical Parasitology 129, 167177.Google Scholar
Fajtová, P., Štefanić, S., Hradilek, M., Dvořák, J., Vondrášek, J., Jílková, A., Ulrychová, L., McKerrow, J. H., Caffrey, C. R., Mareš, M. and Horn, M. (2015). Prolyl Oligopeptidase from the Blood Fluke Schistosoma mansoni: from functional analysis to anti-schistosomal inhibitors. PLOS Neglected Tropical Diseases 9, e0003827.CrossRefGoogle ScholarPubMed
Fülöp, V., Böcskei, Z. and Polgár, L. (1998). Prolyl oligopeptidase: an unusual beta-propeller domain regulates proteolysis. Cell 94, 161170.CrossRefGoogle ScholarPubMed
Gamble, H. R., Fetterer, R. H. and Mansfield, L. S. (1996). Developmentally regulated zinc metalloproteinases from third- and fourth-stage larvae of the ovine nematode Haemonchus contortus . Journal of Parasitology 82, 197202.Google Scholar
Gardner, M. P., Gems, D. and Viney, M. E. (2004). Aging in a very short-lived nematode. Experimental Gerontology 39, 12671276.Google Scholar
Gardner, M. P., Gems, D. and Viney, M. E. (2006). Extraordinary plasticity in aging in Strongyloides ratti implies a gene-regulatory mechanism of lifespan evolution. Aging Cell 5, 315323.Google Scholar
Gass, J. and Khosla, C. (2007). Prolyl endopeptidases. Cellular and Molecular Life Sciences 64, 345355.Google Scholar
Gibney, G., Camp, S., Dionne, M., MacPhee-Quigley, K. and Taylor, P. (1990). Mutagenesis of essential functional residues in acetylcholinesterase. Proceedings of the National Academy of Sciences of the United States of America 87, 75467550.CrossRefGoogle ScholarPubMed
Goud, G. N., Bottazzi, M. E., Zhan, B., Mendez, S., Deumic, V., Plieskatt, J., Liu, S., Wang, Y., Bueno, L., Fujiwara, R., Samuel, A., Ahn, S. Y., Solanki, M., Asojo, O. A., Wang, J., Bethony, J. M., Loukas, A., Roy, M. and Hotez, P. J. (2005). Expression of the Necator americanus hookworm larval antigen Na-ASP-2 in Pichia pastoris and purification of the recombinant protein for use in human clinical trials. Vaccine 23, 47544764.Google Scholar
Grellier, P., Vendeville, S., Joyeau, R., Bastos, I. M. D., Drobecq, H., Frappier, F., Teixeira, A. R. L., Schrevel, J., Davioud-Charvet, E., Sergheraert, C. and Santana, J. M. (2001). Trypanosoma cruzi prolyl oligopeptidase Tc80 is involved in nonphagocytic mammalian cell invasion by trypomastigotes. Journal of Biological Chemistry 276, 4707847086.Google Scholar
Grisaru, D., Sternfeld, M., Eldor, A., Glick, D. and Soreq, H. (1999). Structural roles of acetylcholinesterase variants in biology and pathology. European Journal of Biochemistry 264, 672686.Google Scholar
Hammond, M. P. and Robinson, R. D. (1994). Chromosome complement, gametogenesis, and development of Strongyloides stercoralis . Journal of Parasitology 80, 689695.Google Scholar
Hartmann, S. and Lucius, R. (2003). Modulation of host immune responses by nematode cystatins. International Journal for Parasitology 33, 12911302.CrossRefGoogle ScholarPubMed
Hartmann, S., Schönemeyer, A., Sonnenburg, B., Vray, B. and Lucius, R. (2002). Cystatins of filarial nematodes up-regulate the nitric oxide production of interferon-gamma-activated murine macrophages. Parasite Immunology 24, 253262.Google Scholar
Hawdon, J. M., Jones, B. F., Hoffman, D. R. and Hotez, P. J. (1996). Cloning and characterization of Ancylostoma-secreted protein. A novel protein associated with the transition to parasitism by infective hookworm larvae. Journal of Biological Chemistry 271, 66726678.Google Scholar
Hewitson, J. P., Harcus, Y. M., Curwen, R. S., Dowle, A. A., Atmadja, A. K., Ashton, P. D., Wilson, A. and Maizels, R. M. (2008). The secretome of the filarial parasite, Brugia malayi: proteomic profile of adult excretory-secretory products. Molecular and Biochemical Parasitology 160, 821.Google Scholar
Hewitson, J. P., Grainger, J. R. and Maizels, R. M. (2009). Helminth immunoregulation: the role of parasite secreted proteins in modulating host immunity. Molecular and Biochemical Parasitology 167, 111.Google Scholar
Hewitson, J. P., Harcus, Y., Murray, J., van Agtmaal, M., Filbey, K. J., Grainger, J. R., Bridgett, S., Blaxter, M. L., Ashton, P. D., Ashford, D. A., Curwen, R. S., Wilson, R. A., Dowle, A. A. and Maizels, R. M. (2011). Proteomic analysis of secretory products from the model gastrointestinal nematode Heligmosomoides polygyrus reveals dominance of venom allergen-like (VAL) proteins. Journal of Proteomics 74, 15731594.CrossRefGoogle ScholarPubMed
Hino, A., Tanaka, T., Takaishi, M., Fujii, Y., Palomares-Rius, J. E., Hasegawa, K., Maruyama, H. and Kikuchi, T. (2014). Karyotype and reproduction mode of the rodent parasite Strongyloides venezuelensis . Parasitology 141, 17361745.Google Scholar
Hishida, R., Ishihara, T., Kondo, K. and Katsura, I. (1996). hch-1, a gene required for normal hatching and normal migration of a neuroblast in C. elegans, encodes a protein related to TOLLOID and BMP-1. EMBO Journal 15, 41114122.Google Scholar
Hunt, V. L., Tsai, I. J., Coghlan, A., Reid, A. J., Holroyd, N., Foth, B. J., Tracey, A., Cotton, J. A., Stanley, E. J., Beasley, H., Bennett, H. M., Brooks, K., Harsha, B., Kajitani, R., Kulkarni, A., Harbecke, D., Nagayasu, E., Nichol, S., Ogura, Y., Quail, M. A., Randle, N., Xia, D., Brattig, N. W., Soblik, H., Ribeiro, D. M., Sanchez-Flores, A., Hayashi, T., Itoh, T., Denver, D. R., Grant, W., Stoltzfus, J. D., Lok, J. B., Murayama, H., Wastling, J., Streit, A., Kikuchi, T., Viney, M. and Berriman, M. (2016). The genomic basis of parasitism in the Strongyloides clade of nematodes. Nature Genetics 48, 299307.Google Scholar
Huntington, J. A., Read, R. J. and Carrell, R. W. (2000). Structure of a serpin–protease complex shows inhibition by deformation. Nature 407, 923926.Google Scholar
Hussein, A. S., Chacón, M. R., Smith, A. M., Tosado-Acevedo, R. and Selkirk, M. E. (1999). Cloning, expression, and properties of a nonneuronal secreted acetylcholinesterase from the parasitic nematode Nippostrongylus brasiliensis . Journal of Biological Chemistry 274, 93129319.Google Scholar
Hussein, A. S., Smith, A. M., Chacon, M. R. and Selkirk, M. E. (2000). Determinants of substrate specificity of a second non-neuronal secreted acetylcholinesterase from the parasitic nematode Nippostrongylus brasiliensis . European Journal of Biochemistry 267, 22762282.Google Scholar
Hussein, A. S., Harel, M. and Selkirk, M. E. (2002). A distinct family of acetylcholinesterases is secreted by Nippostrongylus brasiliensis: Molecular and Biochemical Parasitology 123, 125134.Google Scholar
Irving, J. A. (2000). Phylogeny of the Serpin superfamily: implications of patterns of amino acid conservation for structure and function. Genome Research 10, 18451864.CrossRefGoogle ScholarPubMed
Irving, J. A., Pike, R. N., Dai, W., Brömme, D., Worrall, D. M., Silverman, G. A., Coetzer, T. H. T., Dennison, C., Bottomley, S. P. and Whisstock, J. C. (2002). Evidence that serpin architecture intrinsically supports papain-like cysteine protease inhibition: engineering alpha(1)-antitrypsin to inhibit cathepsin proteases. Biochemistry 41, 49985004.Google Scholar
Jacob, J., Vanholme, B., Haegeman, A. and Gheysen, G. (2007). Four transthyretin-like genes of the migratory plant-parasitic nematode Radopholus similis: members of an extensive nematode-specific family. Gene 402, 919.CrossRefGoogle ScholarPubMed
Johnson, C. D., Duckett, J. G., Culotti, J. G., Herman, R. K., Meneely, P. M. and Russell, R. L. (1981). An acetylcholinesterase-deficient mutant of the nematode Caenorhabditis elegans . Genetics 97, 261279.Google Scholar
Johnson, C. D., Rand, J. B., Herman, R. K., Stern, B. D. and Russell, R. L. (1988). The acetylcholinesterase genes of C. elegans: identification of a third gene (ace-3) and mosaic mapping of a synthetic lethal phenotype. Neuron 1, 165173.Google Scholar
Jolodar, A., Fischer, P., Büttner, D. W., Miller, D. J., Schmetz, C. and Brattig, N. W. (2004). Onchocerca volvulus: expression and immunolocalization of a nematode cathepsin D-like lysosomal aspartic protease. Experimental Parasitology 107, 145156.Google Scholar
Knox, D. P. (2007). Proteinase inhibitors and helminth parasite infection. Parasite Immunology 29, 5771.Google Scholar
Koelsch, G., Mares, M., Metcalf, P. and Fusek, M. (1994). Multiple functions of pro-parts of aspartic proteinase zymogens. FEBS Letters 343, 610.Google Scholar
Kolson, D. L. and Russell, R. L. (1985). A novel class of acetylcholinesterase, revealed by mutations, in the nematode Caenorhabditis elegans . Journal of Neurogenetics 2, 93110.Google Scholar
Law, R. H. P., Zhang, Q., McGowan, S., Buckle, A. M., Silverman, G. A., Wong, W., Rosado, C. J., Langendorf, C. G., Pike, R. N., Bird, P. I. and Whisstock, J. C. (2006). An overview of the serpin superfamily. Genome Biology 7, 216.Google Scholar
Lazari, O., Hussein, A. S., Selkirk, M. E., Davidson, A. J., Thompson, F. J. and Matthews, J. B. (2003). Cloning and expression of two secretory acetylcholinesterases from the bovine lungworm, Dictyocaulus viviparus . Molecular and Biochemical Parasitology 132, 8392.Google Scholar
Lee, D. L. (1970). The fine structure of the excretory system in adult Nippostrongylus brasiliensis (Nematoda) and a suggested function for the “excretory glands”. Tissue & Cell 2, 225231.Google Scholar
Lee, D. L. (1996). Why do some nematode parasites of the alimentary tract secrete acetylcholinesterase? International Journal for Parasitology 26, 499508.Google Scholar
Lercher, M. J., Blumenthal, T. and Hurst, L. D. (2003). Coexpression of neighboring genes in Caenorhabditis elegans is mostly due to operons and duplicate genes. Genome Research 13, 238243.CrossRefGoogle ScholarPubMed
Li, X., Shao, H., Junio, A., Nolan, T. J., Massey, H. C., Pearce, E. J., Viney, M. E. and Lok, J. B. (2011). Transgenesis in the parasitic nematode Strongyloides ratti . Molecular and Biochemical Parasitology 179, 114119.CrossRefGoogle ScholarPubMed
Lin, B., Zhuo, K., Chen, S., Hu, L., Sun, L., Wang, X., Zhang, L.-H. and Liao, J. (2016). A novel nematode effector suppresses plant immunity by activating host reactive oxygen species-scavenging system. New Phytologist 209, 11591173.Google Scholar
Loewenstein-Lichtenstein, Y., Glick, D., Gluzman, N., Sternfeld, M., Zakut, H. and Soreq, H. (1996). Overlapping drug interaction sites of human Butyryicholinesterase dissected by site-directed mutagenesis. Molecular Pharmacology 50, 14231431.Google Scholar
Loukas, A., Bethony, J. M., Mendez, S., Fujiwara, R. T., Goud, G. N., Ranjit, N., Zhan, B., Jones, K., Bottazzi, M. E. and Hotez, P. J. (2005). Vaccination with recombinant aspartic hemoglobinase reduces parasite load and blood loss after hookworm infection in dogs. PLoS Medicine 2, e295.Google Scholar
Maizels, R. M. and Yazdanbakhsh, M. (2003). Immune regulation by helminth parasites: cellular and molecular mechanisms. Nature Reviews Immunology 3, 733744.Google Scholar
Maizels, R. M., McSorley, H. J. and Smyth, D. J. (2014). Helminths in the hygiene hypothesis: sooner or later? Clinical and Experimental Immunology 177, 3846.Google Scholar
Manoury, B., Gregory, W. F., Maizels, R. M. and Watts, C. (2001). Bm-CPI-2, a cystatin homolog secreted by the filarial parasite Brugia malayi, inhibits class II MHC-restricted antigen processing. Current Biology 11, 447451.Google Scholar
McKerrow, J. H., Brindley, P., Brown, M., Gam, A. A., Staunton, C. and Neva, F. A. (1990). Strongyloides stercoralis: identification of a protease that facilitates penetration of skin by the infective larvae. Experimental Parasitology 70, 134143.Google Scholar
McKeand, J. B., Knox, D. P., Duncan, J. L. and Kennedy, M. W. (1994). The immunogenicity of the acetylcholinesterases of the cattle lungworm Dictyocaulus viviparus . International Journal for Parasitology 24, 501510.Google Scholar
McSorley, H. J., Hewitson, J. P. and Maizels, R. M. (2013). Immunomodulation by helminth parasites: defining mechanisms and mediators. International Journal for Parasitology 43, 301310.Google Scholar
Mello, L. V., O'Meara, H., Rigden, D. J. and Paterson, S. (2009). Identification of novel aspartic proteases from Strongyloides ratti and characterisation of their evolutionary relationships, stage-specific expression and molecular structure. BMC Genomics 10, 611.Google Scholar
Menon, R., Gasser, R. B., Mitreva, M. and Ranganathan, S. (2012). An analysis of the transcriptome of Teladorsagia circumcincta: its biological and biotechnological implications. BMC Genomics 13, S10.Google Scholar
Mitreva, M., McCarter, J. P., Martin, J., Dante, M., Wylie, T., Chiapelli, B., Pape, D., Clifton, S. W., Nutman, T. B. and Waterston, R. H. (2004). Comparative genomics of gene expression in the parasitic and free-living nematodes Strongyloides stercoralis and Caenorhabditis elegans . Genome Research 14, 209220.CrossRefGoogle ScholarPubMed
Mitreva, M., Jasmer, D. P., Zarlenga, D. S., Wang, Z., Abubucker, S., Martin, J., Taylor, C. M., Yin, Y., Fulton, L., Minx, P., Yang, S.-P., Warren, W. C., Fulton, R. S., Bhonagiri, V., Zhang, X., Hallsworth-Pepin, K., Clifton, S. W., McCarter, J. P., Appleton, J., Mardis, E. R. and Wilson, R. K. (2011). The draft genome of the parasitic nematode Trichinella spiralis . Nature Genetics 43, 228235.Google Scholar
Moyle, M., Foster, D. L., McGrath, D. E., Brown, S. M., Laroche, Y., De Meutter, J., Stanssens, P., Bogowitz, C. A., Fried, V. A. and Ely, J. A. (1994). A hookworm glycoprotein that inhibits neutrophil function is a ligand of the integrin CD11b/CD18. Journal of Biological Chemistry 269, 1000810015.Google Scholar
Mulvenna, J., Hamilton, B., Nagaraj, S. H., Smyth, D., Loukas, A. and Gorman, J. J. (2009). Proteomics analysis of the excretory/secretory component of the blood-feeding stage of the hookworm, Ancylostoma caninum . Molecular & Cellular Proteomics 8, 109121.Google Scholar
Nisbet, A. J., McNeilly, T. N., Wildblood, L. A., Morrison, A. A., Bartley, D. J., Bartley, Y., Longhi, C., McKendrick, I. J., Palarea-Albaladejo, J. and Matthews, J. B. (2013). Successful immunization against a parasitic nematode by vaccination with recombinant proteins. Vaccine 31, 40174023.Google Scholar
Novelli, J., Page, A. P. and Hodgkin, J. (2006). The C terminus of collagen SQT-3 has complex and essential functions in nematode collagen assembly. Genetics 172, 22532267.CrossRefGoogle Scholar
Ogilvie, B. M., Rothwell, T. L. W., Bremmer, K. C., Schnitzerling, H. J., Nolan, J. and Keith, R. K. (1973). Acetylcholinesterase secretion by parasitic nematodes. I. Evidence for secretion of the enzyme by a number of species. International Journal for Parasitology 3, 589597.Google Scholar
Ollis, D. L., Cheah, E., Cygler, M., Dijkstra, B., Frolow, F., Sybille, M., Harel, M., James Remington, S., Silman, I., Schrag, J., Sussman, J. L., Koen, H. G. V. and Goldman, A. (1992). The alpha/ beta hydrolase fold. Protein Engineering, Design and Selection 5, 197211.Google Scholar
Ordentlich, A., Barak, D., Kronman, C., Ariel, N., Segall, Y., Velan, B. and Shafferman, A. (1995). Contribution of aromatic moieties of tyrosine 133 and of the anionic subsite tryptophan 86 to catalytic efficiency and allosteric modulation of acetylcholinesterase. Journal of Biological Chemistry 270, 20822091.Google Scholar
Page, A. P. and Winter, A. D. (2003). Enzymes involved in the biogenesis of the nematode cuticle. Advances in Parasitology 53, 85148.Google Scholar
Page, A. P., Stepek, G., Winter, A. D. and Pertab, D. (2014). Enzymology of the nematode cuticle: a potential drug target? International Journal for Parasitology. Drugs and Drug Resistance 4, 133141.Google Scholar
Pemberton, P. A., Stein, P. E., Pepys, M. B., Potter, J. M. and Carrell, R. W. (1988). Hormone binding globulins undergo serpin conformational change in inflammation. Nature 336, 257258.Google Scholar
Pfaff, A. W., Schulz-Key, H., Soboslay, P. T., Taylor, D. W., MacLennan, K. and Hoffmann, W. H. (2002). Litomosoides sigmodontis cystatin acts as an immunomodulator during experimental filariasis. International Journal for Parasitology 32, 171178.Google Scholar
Power, D. M., Elias, N. P., Richardson, S. J., Mendes, J., Soares, C. M. and Santos, C. R. (2000). Evolution of the thyroid hormone-binding protein, transthyretin. General and Comparative Endocrinology 119, 241255.Google Scholar
Radić, Z., Gibney, G., Kawamoto, S., MacPhee-Quigley, K., Bongiorno, C. and Taylor, P. (1992). Expression of recombinant acetylcholinesterase in a baculovirus system: kinetic properties of glutamate 199 mutants. Biochemistry 31, 97609767.Google Scholar
Ramazzina, I., Folli, C., Secchi, A., Berni, R. and Percudani, R. (2006). Completing the uric acid degradation pathway through phylogenetic comparison of whole genomes. Nature Chemical Biology 2, 144148.Google Scholar
Rand, J. B. and Nonet, M. L. (1997). Neurotransmitter assignents for specific neurons. In C. elegans II (ed. Riddle, D. L., Blumenthal, T., Meyer, B. J. and Priess, J. R.), Cold Spring Harbor, New York. Cold Spring Harbor Laboratory Press. Pages 10491052.Google Scholar
Rawlings, N. D., Tolle, D. P. and Barrett, A. J. (2004). Evolutionary families of peptidase inhibitors. Biochemical Journal 378, 705716.Google Scholar
Rawlings, N. D., Barrett, A. J. and Bateman, A. (2010). MEROPS: the peptidase database. Nucleic Acids Research 38, D227D233.Google Scholar
Ray, C. A., Black, R. A., Kronheim, S. R., Greenstreet, T. A., Sleath, P. R., Salvesen, G. S. and Pickup, D. J. (1992). Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme. Cell 69, 597604.Google Scholar
Santos, L. O., Garcia-Gomes, A. S., Catanho, M., Sodre, C. L., Santos, A. L. S., Branquinha, M. H. and d'Avila-Levy, C. M. (2013). Aspartic peptidases of human pathogenic trypanosomatids: perspectives and trends for chemotherapy. Current Medicinal Chemistry 20, 31163133.Google Scholar
Sauer-Eriksson, A. E., Linusson, A. and Lundberg, E. (2009). Transthyretin-related and transthyretin-like proteins. In Recent Advances in Transthyretin Evolution, Structure and Biological Functions (ed. Richardson, S. J. and Cody, V.). Heidelberg, Germany. Springer Berlin Heidelberg. Pages 109122.Google Scholar
Schwarz, E. M., Korhonen, P. K., Campbell, B. E., Young, N. D., Jex, A. R., Jabbar, A., Hall, R. S., Mondal, A., Howe, A. C., Pell, J., Hofmann, A., Boag, P. R., Zhu, X.-Q., Gregory, T., Loukas, A., Williams, B. A., Antoshechkin, I., Brown, C., Sternberg, P. W. and Gasser, R. B. (2013). The genome and developmental transcriptome of the strongylid nematode Haemonchus contortus . Genome Biology 14, R89.Google Scholar
Schwarz, E. M., Hu, Y., Antoshechkin, I., Miller, M. M., Sternberg, P. W. and Aroian, R. V. (2015). The genome and transcriptome of the zoonotic hookworm Ancylostoma ceylanicum identify infection-specific gene families. Nature Genetics 47, 416422.Google Scholar
Segerberg, M. A. and Stretton, A. O. W. (1993). Actions of cholinergic drugs in the nematode Ascaris suum. Complex pharmacology of muscle and motorneuron. Journal of .General Physiology 101, 271286.Google Scholar
Selkirk, M. E., Lazari, O. and Matthews, J. B. (2005). Functional genomics of nematode acetylcholinesterases. Parasitology 131, S318.Google Scholar
Shafferman, A., Velan, B., Ordentlich, A., Kronman, C., Grosfeld, H., Leitner, M., Flashner, Y., Cohen, S., Barak, D. and Ariel, N. (1992). Substrate inhibition of acetylcholinesterase: residues affecting signal transduction from the surface to the catalytic center. EMBO Journal 11, 35613568.Google Scholar
Shao, H., Li, X., Nolan, T. J., Massey, H. C., Pearce, E. J. and Lok, J. B. (2012). Transposon-mediated chromosomal integration of transgenes in the parasitic nematode Strongyloides ratti and establishment of stable transgenic lines. PLoS Pathogens 8, e1002871.Google Scholar
Sharma, A., Eapen, A. and Subbarao, S. K. (2005). Purification and characterization of a hemoglobin degrading aspartic protease from the malarial parasite Plasmodium vivax . Journal of Biochemistry 138, 7178.Google Scholar
Shaw, R. J., McNeill, M. M., Maass, D. R., Hein, W. R., Barber, T. K., Wheeler, M., Morris, C. A. and Shoemaker, C. B. (2003). Identification and characterisation of an aspartyl protease inhibitor homologue as a major allergen of Trichostrongylus colubriformis . International Journal for Parasitology 33, 12331243.CrossRefGoogle Scholar
Soblik, H., Younis, A. E., Mitreva, M., Renard, B. Y., Kirchner, M., Geisinger, F., Steen, H. and Brattig, N. W. (2011). Life cycle stage-resolved proteomic analysis of the excretome/secretome from Strongyloides ratti-identification of stage-specific proteases. Molecular & Cellular Proteomics 10, M111.010157.Google Scholar
Sonnhammer, E. L. and Durbin, R. (1997). Analysis of protein domain families in Caenorhabditis elegans . Genomics 46, 200216.Google Scholar
Stassens, P., Bergum, P. W., Gansemans, Y., Jespers, L., Laroche, Y., Huang, S., Maki, S., Messens, J., Lauwereys, M., Cappello, M., Hotez, P. J., Lasters, I. and Vlasuk, G. P. (1996). Anticoagulant repertoire of the hookworm Ancylostoma caninum . Proceedings of the National Academy of Sciences of the United States of America 93, 21492154.Google Scholar
Stepek, G., McCormack, G., Winter, A. D. and Page, A. P. (2015). A highly conserved, inhibitable astacin metalloprotease from Teladorsagia circumcincta is required for cuticle formation and nematode development. International Journal for Parasitology 45, 345355.Google Scholar
Sun, Y., Liu, G., Li, Z., Chen, Y., Liu, Y., Liu, B. and Su, Z. (2013). Modulation of dendritic cell function and immune response by cysteine protease inhibitor from murine nematode parasite Heligmosomoides polygyrus . Immunology 138, 370381.Google Scholar
Sussman, J. L., Harel, M., Frolow, F., Oefner, C., Goldmant, A., Toker, L. and Silman, I. (1991). Acetyicholinesterase from Torpedo calfornica: a prototypic acetyicholine-binding protein. Science 253, 872879.Google Scholar
Suzuki, M., Sagoh, N., Iwasaki, H., Inoue, H. and Takahashi, K. (2004). Metalloproteases with EGF, CUB, and thrombospondin-1 domains function in molting of Caenorhabditis elegans . Biological Chemistry 385, 565568.Google Scholar
Tang, Y. T., Gao, X., Rosa, B. A., Abubucker, S., Hallsworth-Pepin, K., Martin, J., Tyagi, R., Heizer, E., Zhang, X., Bhonagiri-Palsikar, V., Minx, P., Warren, W. C., Wang, Q., Zhan, B., Hotez, P. J., Sternberg, P. W., Dougall, A., Gaze, S. T., Mulvenna, J., Sotillo, J., Ranganathan, S., Rabelo, E. M., Wilson, R. K., Felgner, P. L., Bethony, J., Hawdon, J. M., Gasser, R. B., Loukas, A. and Mitreva, M. (2014). Genome of the human hookworm Necator americanus . Nature Genetics 46, 261269.Google Scholar
Tort, J., Brindley, P. J., Knox, D., Wolfe, K. H. and Dalton, J. P. (1999). Proteinases and associated genes of parasitic helminths. Advances in Parasitology 43, 161266.Google Scholar
Tracey, K. J. (2009). Reflex control of immunity. Nature Reviews Immunology 9, 418428.CrossRefGoogle ScholarPubMed
Valdivieso, E., Perteguer, M. J., Hurtado, C., Campioli, P., Rodríguez, E., Saborido, A., Martínez-Sernández, V., Gómez-Puertas, P., Ubeira, F. M. and Gárate, T. (2015). ANISERP: a new serpin from the parasite Anisakis simplex . Parasites & Vectors 8, 399.Google Scholar
Viney, M. E. (1994). A genetic analysis of reproduction in Strongyloides ratti . Parasitology 109, 511515.Google Scholar
Wang, E. A., Rosen, V., Cordes, P., Hewick, R. M., Kriz, M. J., Luxenberg, D. P., Sibley, B. S. and Wozney, J. M. (1988). Purification and characterization of other distinct bone-inducing factors. Proceedings of the National Academy of Sciences of the United States of America 85, 94849488.Google Scholar
Wang, H., Yu, M., Ochani, M., Amella, C. A., Tanovic, M., Susarla, S., Li, J. H., Wang, H., Yang, H., Ulloa, L., Al-Abed, Y., Czura, C. J. and Tracey, K. J. (2003). Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 421, 384388.Google Scholar
Wang, X., Li, W., Zhao, D., Liu, B., Shi, Y., Chen, B., Yang, H., Guo, P., Geng, X., Shang, Z., Peden, E., Kage-Nakadai, E., Mitani, S. and Xue, D. (2010). Caenorhabditis elegans transthyretin-like protein TTR-52 mediates recognition of apoptotic cells by the CED-1 phagocyte receptor. Nature Cell Biology 12, 655664.Google Scholar
Wang, T., Van Steendam, K., Dhaenens, M., Vlaminck, J., Deforce, D., Jex, A. R., Gasser, R. B. and Geldhof, P. (2013). Proteomic analysis of the excretory-secretory products from larval stages of Ascaris suum reveals high abundance of glycosyl hydrolases. PLoS Neglected Tropical Diseases 7, e2467.Google Scholar
Wang, S., Wei, W., Luo, X., Wang, S., Hu, S. and Cai, X. (2015). Comparative genomic analysis of aspartic proteases in eight parasitic platyhelminths: insights into functions and evolution. Gene 559, 5261.Google Scholar
Ward, J. D. (2015). Rendering the intractable more tractable: tools from Caenorhabditis elegans ripe for import into parasitic nematodes. Genetics 201, 12791294.Google Scholar
Whelan, R. A. K., Hartmann, S. and Rausch, S. (2012). Nematode modulation of inflammatory bowel disease. Protoplasma 249, 871886.Google Scholar
Williamson, A. L., Brindley, P. J., Abbenante, G., Prociv, P., Berry, C., Girdwood, K., Pritchard, D. I., Fairlie, D. P., Hotez, P. J., Dalton, J. P. and Loukas, A. (2002). Cleavage of hemoglobin by hookworm cathepsin D aspartic proteases and its potential contribution to host specificity. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology 16, 14581460.Google Scholar
Williamson, A. L., Lustigman, S., Oksov, Y., Deumic, V., Plieskatt, J., Mendez, S., Zhan, B., Bottazzi, M. E., Hotez, P. J. and Loukas, A. (2006). Ancylostoma caninum MTP-1, an astacin-like metalloprotease secreted by infective hookworm larvae, is involved in tissue migration. Infection and Immunity 74, 961967.Google Scholar
Wilson, M. S., Taylor, M. D., O'Gorman, M. T., Balic, A., Barr, T. A., Filbey, K., Anderton, S. M. and Maizels, R. M. (2010). Helminth-induced CD19+CD23hi B cells modulate experimental allergic and autoimmune inflammation. European Journal of Immunology 40, 16821696.CrossRefGoogle ScholarPubMed
Zang, X. and Maizels, R. M. (2001). Serine proteinase inhibitors from nematodes and the arms race between host and pathogen. Trends in Biochemical Sciences 26, 191197.Google Scholar
Zang, X., Yazdanbakhsh, M., Jiang, H., Kanost, M. R. and Maizels, R. M. (1999). A novel serpin expressed by blood-borne microfilariae of the parasitic nematode Brugia malayi inhibits human neutrophil serine proteinases. Blood 94, 14181428.Google Scholar