Skip to main content Accessibility help

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



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.


Corresponding author

*Corresponding author: School of Biological Sciences, Life Sciences Building, University of Bristol, Bristol BS8 1TQ, UK. E-mail:


Hide All
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.
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.
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.
Asojo, O. A. (2011). Structure of a two-CAP-domain protein from the human hookworm parasite Necator americanus . Acta crystallographica., Biological Crystallography 67, 455462.
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.
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.
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.
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.
Bolla, R. I. and Roberts, L. S. (1968). Gametogenesis and chromosomal complement in Strongyloides ratti (Nematoda: Rhabdiasoidea). Journal of Parasitology 54, 849855.
Bond, J. S. and Beynon, R. J. (1995). The astacin family of metalloendopeptidases. Protein Science 4, 12471261.
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.
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.
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.
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.
Cantacessi, C. and Gasser, R. B. (2012). SCP/TAPS proteins in helminths – where to from now? Molecular and Cellular Probes 26, 5459.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Fülöp, V., Böcskei, Z. and Polgár, L. (1998). Prolyl oligopeptidase: an unusual beta-propeller domain regulates proteolysis. Cell 94, 161170.
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.
Gardner, M. P., Gems, D. and Viney, M. E. (2004). Aging in a very short-lived nematode. Experimental Gerontology 39, 12671276.
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.
Gass, J. and Khosla, C. (2007). Prolyl endopeptidases. Cellular and Molecular Life Sciences 64, 345355.
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.
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.
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.
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.
Hammond, M. P. and Robinson, R. D. (1994). Chromosome complement, gametogenesis, and development of Strongyloides stercoralis . Journal of Parasitology 80, 689695.
Hartmann, S. and Lucius, R. (2003). Modulation of host immune responses by nematode cystatins. International Journal for Parasitology 33, 12911302.
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.
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.
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.
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.
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.
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.
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.
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.
Huntington, J. A., Read, R. J. and Carrell, R. W. (2000). Structure of a serpin–protease complex shows inhibition by deformation. Nature 407, 923926.
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.
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.
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.
Irving, J. A. (2000). Phylogeny of the Serpin superfamily: implications of patterns of amino acid conservation for structure and function. Genome Research 10, 18451864.
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.
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.
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.
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.
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.
Knox, D. P. (2007). Proteinase inhibitors and helminth parasite infection. Parasite Immunology 29, 5771.
Koelsch, G., Mares, M., Metcalf, P. and Fusek, M. (1994). Multiple functions of pro-parts of aspartic proteinase zymogens. FEBS Letters 343, 610.
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.
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.
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.
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.
Lee, D. L. (1996). Why do some nematode parasites of the alimentary tract secrete acetylcholinesterase? International Journal for Parasitology 26, 499508.
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.
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.
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.
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.
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.
Maizels, R. M. and Yazdanbakhsh, M. (2003). Immune regulation by helminth parasites: cellular and molecular mechanisms. Nature Reviews Immunology 3, 733744.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Page, A. P. and Winter, A. D. (2003). Enzymes involved in the biogenesis of the nematode cuticle. Advances in Parasitology 53, 85148.
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.
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.
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.
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.
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.
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.
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.
Rawlings, N. D., Tolle, D. P. and Barrett, A. J. (2004). Evolutionary families of peptidase inhibitors. Biochemical Journal 378, 705716.
Rawlings, N. D., Barrett, A. J. and Bateman, A. (2010). MEROPS: the peptidase database. Nucleic Acids Research 38, D227D233.
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.
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.
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.
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.
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.
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.
Selkirk, M. E., Lazari, O. and Matthews, J. B. (2005). Functional genomics of nematode acetylcholinesterases. Parasitology 131, S318.
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.
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.
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.
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.
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.
Sonnhammer, E. L. and Durbin, R. (1997). Analysis of protein domain families in Caenorhabditis elegans . Genomics 46, 200216.
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.
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.
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.
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.
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.
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.
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.
Tracey, K. J. (2009). Reflex control of immunity. Nature Reviews Immunology 9, 418428.
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.
Viney, M. E. (1994). A genetic analysis of reproduction in Strongyloides ratti . Parasitology 109, 511515.
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.
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.
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.
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.
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.
Ward, J. D. (2015). Rendering the intractable more tractable: tools from Caenorhabditis elegans ripe for import into parasitic nematodes. Genetics 201, 12791294.
Whelan, R. A. K., Hartmann, S. and Rausch, S. (2012). Nematode modulation of inflammatory bowel disease. Protoplasma 249, 871886.
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.
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.
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.
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.
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.



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed