Secreted proteomes of different developmental stages of the gastrointestinal nematode Nippostrongylus brasiliensis

Molecular and Cellular Proteomics

Volumn 13, Issue 10, 2014, Pages 2736-2751

  Sotillo, Javier ^a   Sanchez Flores, Alejandro ^b,h   Cantacessi, Cinzia ^a,c   Harcus, Yvonne ^d   Pickering, Darren ^a   Bouchery, Tiffany ^e   Camberis, Mali ^e   Tang, Shiau Choot ^e   Giacomin, Paul ^a   Mulvenna, Jason ^a,f   Mitreva, Makedonka ^g   Berriman, Matthew ^b   LeGros, Graham ^e   Maizels, Rick M ^d   Loukas, Alex ^a  

^a JAMES COOK UNIVERSITY   (Australia)

^b WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

^c UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^d UNIVERSITY OF EDINBURGH   (United Kingdom)

^e MALAGHAN INSTITUTE OF MEDICAL RESEARCH   (New Zealand)

^f QIMR BERGHOFER MEDICAL RESEARCH INSTITUTE   (Australia)

^g WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^h INSTITUTO DE BIOTECNOLOGÍA   (Mexico)

Author keywords

[No Author keywords available]

Indexed keywords

METALLOPROTEINASE; PROTEOME; HELMINTH PROTEIN;

ADULT; ARTICLE; COMPARATIVE STUDY; DATA BASE; DEVELOPMENTAL STAGE; EGG PARASITOID; HOOKWORM INFECTION; HOST PARASITE INTERACTION; IMMUNE RESPONSE; LARVAL STAGE; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; NIPPOSTRONGYLUS BRASILIENSIS; NONHUMAN; NUCLEOTIDE SEQUENCE; PARASITE MIGRATION; PHYLOGENY; PROTEIN ANALYSIS; PROTEIN DOMAIN; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN SECRETION; PROTEOMICS; TRANSCRIPTOMICS; ANIMAL; CONSERVED SEQUENCE; GASTROINTESTINAL TRACT; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GROWTH, DEVELOPMENT AND AGING; HOOKWORM; LIFE CYCLE STAGE; METABOLISM; PARASITOLOGY; PROCEDURES; RAT; SECRETION (PROCESS); SEQUENCE ANALYSIS; SPRAGUE DAWLEY RAT;

NIPPOSTRONGYLUS BRASILIENSIS;

ANCYLOSTOMATOIDEA; ANIMALS; BASE SEQUENCE; CONSERVED SEQUENCE; GASTROINTESTINAL TRACT; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, DEVELOPMENTAL; HELMINTH PROTEINS; LIFE CYCLE STAGES; PHYLOGENY; PROTEOME; PROTEOMICS; RATS; RATS, SPRAGUE-DAWLEY; SEQUENCE ANALYSIS, RNA;

EID: 84907960594     PISSN: 15359476     EISSN: 15359484     Source Type: Journal    
DOI: 10.1074/mcp.M114.038950     Document Type: Article

References (86)

1. Hotez, P. J., Brooker, S., Bethony, J. M., Bottazzi, M. E., Loukas, A., and Xiao, S. (2004) Hookworm infection. N. Engl. J. 351, 799-807
2. Hotez, P. J., Fenwick, A., Savioli, L., and Molyneux, D. H. (2009) Rescuing the bottom billion through control of neglected tropical diseases. Lancet 373, 1570-1575
3. World Health Organization. Global Health Estimates (GHE) 2013: DALYs by age, sex and cause. DALY estimates, 2000-2011. Geneva: World Health Organization, November 2013
4. Camberis, M., Le Gros, G., and Urban, J., Jr. (2003) Animal model of Nippostrongylus brasiliensis and Heligmosomoides polygyrus. Current protocols in immunology / edited by John E. Coligan. [et al.] Chapter 19, Unit 19 12
5. Ehigiator, H. N., Stadnyk, A. W., and Lee, T. D. (2000) Extract of Nippostrongylus brasiliensis stimulates polyclonal type-2 immunoglobulin response by inducing de novo class switch. Infect. Immun. 68, 4913-4922
6. Holland, M. J., Harcus, Y. M., Riches, P. L., and Maizels, R. M. (2000) Proteins secreted by the parasitic nematode Nippostrongylus brasiliensis act as adjuvants for Th2 responses. Eur. J. Immunol. 30, 1977-1987
7. McSorley, H. J., and Loukas, A. (2010) The immunology of human hookworm infections. Parasite Immunol. 32, 549-559
8. McSorley, H. J., and Maizels, R. M. (2012) Helminth infections and host immune regulation. Clin. Microbiol. Rev. 25, 585-608
9. Ohnmacht, C., and Voehringer, D. (2010) Basophils protect against reinfection with hookworms independently of mast cells and memory Th2 cells. J. Immunol. 184, 344-350
10. Conrad, D. H., Ben-Sasson, S. Z., Le Gros, G., Finkelman, F. D., and Paul, W. E. (1990) Infection with Nippostrongylus brasiliensis or injection of anti-IgD antibodies markedly enhances Fc-receptor-mediated interleukin 4 production by non-B, non-T cells. J. Exp. Med. 171, 1497-1508
11. Harvie, M., Camberis, M., and Le Gros, G. (2013) Development of CD4 T cell dependent immunity against N. brasiliensis infection. Front. Immunol. 4, 74
12. Harvie, M., Camberis, M., Tang, S. C., Delahunt, B., Paul, W., and Le Gros, G. (2010) The lung is an important site for priming CD4 T-cell-mediated protective immunity against gastrointestinal helminth parasites. Infect. Immun. 78, 3753-3762
13. Kopf, M., Le Gros, G., Bachmann, M., Lamers, M. C., Bluethmann, H., and Kohler, G. (1993) Disruption of the murine IL-4 gene blocks Th2 cytokine responses. Nature 362, 245-248
14. Lebrun, P., and Spiegelberg, H. L. (1987) Concomitant immunoglobulin E and immunoglobulin G1 formation in Nippostrongylus brasiliensis-infected mice. J. Immunol. 139, 1459-1465
15. Neill, D. R., Wong, S. H., Bellosi, A., Flynn, R. J., Daly, M., Langford, T. K., Bucks, C., Kane, C. M., Fallon, P. G., Pannell, R., Jolin, H. E., and McKenzie, A. N. (2010) Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity. Nature 464, 1367-1370
16. Shin, E. H., Osada, Y., Chai, J. Y., Matsumoto, N., Takatsu, K., and Kojima, S. (1997) Protective roles of eosinophils in Nippostrongylus brasiliensis infection. Int. Arch. Allergy Immunol. 114, 45-50
17. Harcus, Y. M., Parkinson, J., Fernandez, C., Daub, J., Selkirk, M. E., Blaxter, M. L., and Maizels, R. M. (2004) Signal sequence analysis of expressed sequence tags from the nematode Nippostrongylus brasiliensis and the evolution of secreted proteins in parasites. Genome Biol. 5, R39
18. 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. Nat. Genet. doi: 10.1038/ng.2875
19. Lawrence, R. A., Gray, C. A., Osborne, J., and Maizels, R. M. (1996) Nippostrongylus brasiliensis: cytokine responses and nematode expulsion in normal and IL-4-deficient mice. Exp. Parasitol. 84, 65-73
20. Grabherr, M. G., Haas, B. J., Yassour, M., Levin, J. Z., Thompson, D. A., Amit, I., Adiconis, X., Fan, L., Raychowdhury, R., Zeng, Q., Chen, Z., Mauceli, E., Hacohen, N., Gnirke, A., Rhind, N., di Palma, F., Birren, B. W., Nusbaum, C., Lindblad-Toh, K., Friedman, N., and Regev, A. (2011) Full-length transcriptome assembly from RNA-Seq data without a reference genome. Nat. Biotechnol. 29, 644-652
21. Haas, B. J., Papanicolaou, A., Yassour, M., Grabherr, M., Blood, P. D., Bowden, J., Couger, M. B., Eccles, D., Li, B., Lieber, M., Macmanes, M. D., Ott, M., Orvis, J., Pochet, N., Strozzi, F., Weeks, N., Westerman, R., William, T., Dewey, C. N., Henschel, R., Leduc, R. D., Friedman, N., and Regev, A. (2013) De novo transcript sequence reconstruction from RNA-seq using the Trinity platform for reference generation and analysis. Nat. Protoc. 8, 1494-1512
22. Healer, J., Ashall, F., and Maizels, R. M. (1991) Characterization of proteolytic enzymes from larval and adult Nippostrongylus brasiliensis. Parasitology 103, 305-314
23. 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. Mol. Biochem. Parasitol. 160, 8-21
24. Sotillo, J., Valero, L., Sanchez Del Pino, M. M., Fried, B., Esteban, J. G., Marcilla, A., and Toledo, R. (2008) Identification of antigenic proteins from Echinostoma caproni (Trematoda) recognized by mouse immunoglobulins M, A, and G using an immunoproteomic approach. Parasite Immunol. 30, 271-279
25. Yan, J. X., Wait, R., Berkelman, T., Harry, R. A., Westbrook, J. A., Wheeler, C. H., and Dunn, M. J. (2000) A modified silver staining protocol for visualization of proteins compatible with matrix-assisted laser desorption/ionization and electrospray ionization-mass spectrometry. Electrophoresis 21, 3666-3672
26. 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. Mol. Cell Proteomics 8, 109-121
27. Cantacessi, C., Mulvenna, J., Young, N. D., Kasny, M., Horak, P., Aziz, A., Hofmann, A., Loukas, A., and Gasser, R. B. (2012) A deep exploration of the transcriptome and "excretory/secretory" proteome of adult Fascioloides magna. Mol. Cell Proteomics 11, 1340-1353
28. Searle, B. C. (2010) Scaffold: a bioinformatic tool for validating MS/MS-based proteomic studies. Proteomics 10, 1265-1269
29. Keller, A., Nesvizhskii, A. I., Kolker, E., and Aebersold, R. (2002) Empirical statistical model to estimate the accuracy of peptide identifications made by MS/MS and database search. Anal. Chem. 74, 5383-5392
30. Nesvizhskii, A. I., Keller, A., Kolker, E., and Aebersold, R. (2003) A statistical model for identifying proteins by tandem mass spectrometry. Anal. Chem. 75, 4646-4658
31. Conesa, A., Gotz, S., Garcia-Gomez, J. M., Terol, J., Talon, M., and Robles, M. (2005) Blast2GO: a universal tool for annotation, visualization, and analysis in functional genomics research. Bioinformatics 21, 3674-3676
32. Finn, R. D., Clements, J., and Eddy, S. R. (2011) HMMER web server: interactive sequence similarity searching. Nucleic Acids Res. 39, W29-W37
33. Marchler-Bauer, A., Lu, S., Anderson, J. B., Chitsaz, F., Derbyshire, M. K., DeWeese-Scott, C., Fong, J. H., Geer, L. Y., Geer, R. C., Gonzales, N. R., Gwadz, M., Hurwitz, D. I., Jackson, J. D., Ke, Z., Lanczycki, C. J., Lu, F., Marchler, G. H., Mullokandov, M., Omelchenko, M. V., Robertson, C. L., Song, J. S., Thanki, N., Yamashita, R. A., Zhang, D., Zhang, N., Zheng, C., and Bryant, S. H. (2011) CDD: a Conserved Domain Database for the functional annotation of proteins. Nucleic Acids Res. 39, D225-D229
34. Emanuelsson, O., Brunak, S., von Heijne, G., and Nielsen, H. (2007) Locating proteins in the cell using TargetP, SignalP, and related tools. Nat. Protoc. 2, 953-971
35. Krogh, A., Larsson, B., von Heijne, G., and Sonnhammer, E. L. (2001) Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. J. Mol. Biol. 305, 567-580
36. Blom, N., Sicheritz-Ponten, T., Gupta, R., Gammeltoft, S., and Brunak, S. (2004) Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence. Proteomics 4, 1633-1649
37. Parkinson, J., and Blaxter, M. (2003) SimiTri - visualizing similarity relationships for groups of sequences. Bioinformatics 19, 390-395
38. Cantacessi, C., Mitreva, M., Jex, A. R., Young, N. D., Campbell, B. E., Hall, R. S., Doyle, M. A., Ralph, S. A., Rabelo, E. M., Ranganathan, S., Sternberg, P. W., Loukas, A., and Gasser, R. B. (2010) Massively parallel sequencing and analysis of the Necator americanus transcriptome. PLoS Negl. Trop. Dis. 4, e684
39. 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. J. Proteomics 74, 1573-1594
40. Bennuru, S., Semnani, R., Meng, Z., Ribeiro, J. M., Veenstra, T. D., and Nutman, T. B. (2009) Brugia malayi excreted/secreted proteins at the host/parasite interface: stage- and gender-specific proteomic profiling. PLoS Negl. Trop. Dis. 3, e410
41. Blaxter, M. L., De Ley, P., Garey, J. R., Liu, L. X., Scheldeman, P., Vierstraete, A., Vanfleteren, J. R., Mackey, L. Y., Dorris, M., Frisse, L. M., Vida, J. T., and Thomas, W. K. (1998) A molecular evolutionary framework for the phylum Nematoda. Nature 392, 71-75
42. Abascal, F., Zardoya, R., and Posada, D. (2005) ProtTest: selection of best-fit models of protein evolution. Bioinformatics 21, 2104-2105
43. Tamura, K., Peterson, D., Peterson, N., Stecher, G., Nei, M., and Kumar, S. (2011) MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol. Biol. Evol. 28, 2731-2739
44. Miller, M. A., Pfeiffer, W., and Schwartz, T. "Creating the CIPRES Science Gateway for inference of large phylogenetic trees" in Proceedings of the Gateway Computing Environments Workshop (GCE), 14 Nov. 2010, New Orleans, LA pp 1-8, 8
45. 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. J. Biol. Chem. 271, 6672-6678
46. Murray, J., Gregory, W. F., Gomez-Escobar, N., Atmadja, A. K., and Maizels, R. M. (2001) Expression and immune recognition of Brugia malayi VAL-1, a homolog of vespid venom allergens and Ancylostoma secreted proteins. Mol. Biochem. Parasitol. 118, 89-96
47. Reece, J. J., Siracusa, M. C., Southard, T. L., Brayton, C. F., Urban, J. F., Jr., and Scott, A. L. (2008) Hookworm-induced persistent changes to the immunological environment of the lung. Infect. Immun. 76, 3511-3524
48. Young, N. D., Jex, A. R., Cantacessi, C., Hall, R. S., Campbell, B. E., Spithill, T. W., Tangkawattana, S., Tangkawattana, P., Laha, T., and Gasser, R. B. (2011) A portrait of the transcriptome of the neglected trematode, Fasciola gigantica - biological and biotechnological implications. PLoS Negl. Trop. Dis. 5, e1004
49. Garg, G., Bernal, D., Trelis, M., Forment, J., Ortiz, J., Valero, M. L., Pedrola, L., Martinez-Blanch, J., Esteban, J. G., Ranganathan, S., Toledo, R., and Marcilla, A. (2013) The transcriptome of Echinostoma caproni adults: further characterization of the secretome and identification of new potential drug targets. J. Proteomics 89, 202-214
50. 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. Mol. Cell Proteomics 10, M111 010157
51. Marcilla, A., Trelis, M., Cortes, A., Sotillo, J., Cantalapiedra, F., Minguez, M. T., Valero, M. L., Sanchez del Pino, M. M., Munoz-Antoli, C., Toledo, R., and Bernal, D. (2012) Extracellular vesicles from parasitic helminths contain specific excretory/secretory proteins and are internalized in intestinal host cells. PLoS One 7, e45974
52. Boehnisch, C., Wong, D., Habig, M., Isermann, K., Michiels, N. K., Roeder, T., May, R. C., and Schulenburg, H. (2011) Protist-type lysozymes of the nematode Caenorhabditis elegans contribute to resistance against pathogenic Bacillus thuringiensis. PLoS One 6, e24619
53. Eichinger, L., Pachebat, J. A., Glockner, G., Rajandream, M. A., Sucgang, R., Berriman, M., Song, J., Olsen, R., Szafranski, K., Xu, Q., Tunggal, B., Kummerfeld, S., Madera, M., Konfortov, B. A., Rivero, F., Bankier, A. T., Lehmann, R., Hamlin, N., Davies, R., Gaudet, P., Fey, P., Pilcher, K., Chen, G., Saunders, D., Sodergren, E., Davis, P., Kerhornou, A., Nie, X., Hall, N., Anjard, C., Hemphill, L., Bason, N., Farbrother, P., Desany, B., Just, E., Morio, T., Rost, R., Churcher, C., Cooper, J., Haydock, S., van Driessche, N., Cronin, A., Goodhead, I., Muzny, D., Mourier, T., Pain, A., Lu, M., Harper, D., Lindsay, R., Hauser, H., James, K., Quiles, M., Madan Babu, M., Saito, T., Buchrieser, C., Wardroper, A., Felder, M., Thangavelu, M., Johnson, D., Knights, A., Loulseged, H., Mungall, K., Oliver, K., Price, C., Quail, M. A., Urushihara, H., Hernandez, J., Rabbinowitsch, E., Steffen, D., Sanders, M., Ma, J., Kohara, Y., Sharp, S., Simmonds, M., Spiegler, S., Tivey, A., Sugano, S., White, B., Walker, D., Woodward, J., Winckler, T., Tanaka, Y., Shaulsky, G., Schleicher, M., Weinstock, G., Rosenthal, A., Cox, E. C., Chisholm, R. L., Gibbs, R., Loomis, W. F., Platzer, M., Kay, R. R., Williams, J., Dear, P. H., Noegel, A. A., Barrell, B., and Kuspa, A. (2005) The genome of the social amoeba Dictyostelium discoideum. Nature 435, 43-57
54. Morassutti, A. L., Levert, K., Pinto, P. M., da Silva, A. J., Wilkins, P., and Graeff-Teixeira, C. (2012) Characterization of Angiostrongylus cantonensis excretory-secretory proteins as potential diagnostic targets. Exp. Parasitol. 130, 26-31
55. Sotillo, J., Valero, M. L., Sanchez Del Pino, M. M., Fried, B., Esteban, J. G., Marcilla, A., and Toledo, R. (2010) Excretory/secretory proteome of the adult stage of Echinostoma caproni. Parasitol. Res. 107, 691-697
56. Batra, S., Singh, S. P., Gupta, S., Katiyar, J. C., and Srivastava, V. M. (1990) Reactive oxygen intermediates metabolizing enzymes in Ancylostoma ceylanicum and Nippostrongylus brasiliensis. Free Radic. Biol. Med. 8, 271-274
57. Hewitson, J. P., Ivens, A. C., Harcus, Y., Filbey, K. J., McSorley, H. J., Murray, J., Bridgett, S., Ashford, D., Dowle, A. A., and Maizels, R. M. (2013) Secretion of protective antigens by tissue-stage nematode larvae revealed by proteomic analysis and vaccination-induced sterile immunity. PLoS Pathog. 9, e1003492
58. Nisbet, A. J., Zarlenga, D. S., Knox, D. P., Meikle, L. I., Wildblood, L. A., and Matthews, J. B. (2011) A calcium-activated apyrase from Teladorsagia circumcincta: an excretory/secretory antigen capable of modulating host immune responses? Parasite Immunol. 33, 236-243
59. Valenzuela, J. G., Charlab, R., Galperin, M. Y., and Ribeiro, J. M. (1998) Purification, cloning, and expression of an apyrase from the bed bug Cimex lectularius. A new type of nucleotide-binding enzyme. J. Biol. Chem. 273, 30583-30590
60. Zarlenga, D. S., Nisbet, A. J., Gasbarre, L. C., and Garrett, W. M. (2011) A calcium-activated nucleotidase secreted from Ostertagia ostertagi 4th-stage larvae is a member of the novel salivary apyrases present in blood-feeding arthropods. Parasitology 138, 333-343
61. Hussein, A. S., Chacon, 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. J. Biol. Chem. 274, 9312-9319
62. Lee, D. L. (1996) Why do some nematode parasites of the alimentary tract secrete acetylcholinesterase? Int. J. Parasitol. 26, 499-508
63. Cantacessi, C., Hofmann, A., Pickering, D., Navarro, S., Mitreva, M., and Loukas, A. (2013) TIMPs of parasitic helminths - a large-scale analysis of high-throughput sequence datasets. Parasit. Vectors 6, 156
64. Mitreva, M., McCarter, J. P., Arasu, P., Hawdon, J., Martin, J., Dante, M., Wylie, T., Xu, J., Stajich, J. E., Kapulkin, W., Clifton, S. W., Waterston, R. H., and Wilson, R. K. (2005) Investigating hookworm genomes by comparative analysis of two Ancylostoma species. BMC Genomics 6, 58
65. Zhan, B., Badamchian, M., Meihua, B., Ashcom, J., Feng, J., Hawdon, J., Shuhua, X., and Hotez, P. J. (2002) Molecular cloning and purification of Ac-TMP, a developmentally regulated putative tissue inhibitor of metallo00protease released in relative abundance by adult Ancylostoma hookworms. Am. J. Trop. Med. Hyg. 66, 238-244
66. Cuellar, C., Wu, W., and Mendez, S. (2009) The hookworm tissue inhibitor of metalloproteases (Ac-TMP-1) modifies dendritic cell function and induces generation of CD4 and CD8 suppressor T cells. PLoS Negl. Trop. Dis. 3, e439
67. Bower, M. A., Constant, S. L., and Mendez, S. (2008) Necator americanus: the Na-ASP-2 protein secreted by the infective larvae induces neutrophil recruitment in vivo and in vitro. Exp. Parasitol. 118, 569-575
68. Diemert, D. J., Pinto, A. G., Freire, J., Jariwala, A., Santiago, H., Hamilton, R. G., Periago, M. V., Loukas, A., Tribolet, L., Mulvenna, J., Correa-Oliveira, R., Hotez, P. J., and Bethony, J. M. (2012) Generalized urticaria induced by the Na-ASP-2 hookworm vaccine: implications for the development of vaccines against helminths. J. Allergy Clin. Immunol. 130, 169-176 e166
69. Bond, J. S., and Beynon, R. J. (1995) The astacin family of metalloendopeptidases. Protein Sci. 4, 1247-1261
70. Baska, P., Wisniewski, M., Krzyzowska, M., Dlugosz, E., Zygner, W., Gorski, P., and Wedrychowicz, H. (2013) Molecular cloning and characterisation of in vitro immune response against astacin-like metalloprotease Ace-MTP-2 from Ancylostoma ceylanicum. Exp. Parasitol. 133, 472-482
71. Stepek, G., McCormack, G., Birnie, A. J., and Page, A. P. (2011) The astacin metalloprotease moulting enzyme NAS-36 is required for normal cuticle ecdysis in free-living and parasitic nematodes. Parasitology. 138, 237-248
72. Varatharajalu, R., Parandaman, V., Ndao, M., Andersen, J. F., and Neva, F. A. (2011) Strongyloides stercoralis excretory/secretory protein strongylastacin specifically recognized by IgE antibodies in infected human sera. Microbiol. Immunol. 55, 115-122
73. 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. Infect. Immun. 74, 961-967
74. Hotez, P. J., Ashcom, J., Zhan, B., Bethony, J., Loukas, A., Hawdon, J., Wang, Y., Jin, Q., Jones, K. C., Dobardzic, A., Dobardzic, R., Bolden, J., Essiet, I., Brandt, W., Russell, P. K., Zook, B. C., Howard, B., and Chacon, M. (2003) Effect of vaccination with a recombinant fusion protein encoding an astacinlike metalloprotease (MTP-1) secreted by host-stimulated Ancylostoma caninum third-stage infective larvae. J. Parasitol. 89, 853-855
75. Gomez Gallego, S., Loukas, A., Slade, R. W., Neva, F. A., Varatharajalu, R., Nutman, T. B., and Brindley, P. J. (2005) Identification of an astacin-like metallo-proteinase transcript from the infective larvae of Strongyloides stercoralis. Parasitol. Int. 54, 123-133
76. 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, 6001-6008
77. 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. J. Parasitol. 82, 197-202
78. Guiliano, D. B., Hong, X., McKerrow, J. H., Blaxter, M. L., Oksov, Y., Liu, J., Ghedin, E., and Lustigman, S. (2004) A gene family of cathepsin L-like proteases of filarial nematodes are associated with larval molting and cuticle and eggshell remodeling. Mol. Biochem. Parasitol. 136, 227-242
79. 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. Biotechnol. Adv. 27, 376-388
80. He, Y., Barker, S. J., MacDonald, A. J., Yu, Y., Cao, L., Li, J., Parhar, R., Heck, S., Hartmann, S., Golenbock, D. T., Jiang, S., Libri, N. A., Semper, A. E., Rosenberg, W. M., and Lustigman, S. (2009) Recombinant Ov-ASP-1, a Th1-biased protein adjuvant derived from the helminth Onchocerca volvulus, can directly bind and activate antigen-presenting cells. J. Immunol. 182, 4005-4016
81. Moyle, M., Foster, D. L., McGrath, D. E., Brown, S. M., Laroche, Y., De Meutter, J., Stanssens, P., Bogowitz, C. A., Fried, V. A., Ely, J. A., Soule, H. R., and Vlasuk, G. P. (1994) A hookworm glycoprotein that inhibits neutrophil function is a ligand of the integrin CD11b/CD18. J. Biol. Chem. 269, 10008-10015
82. Osman, A., Wang, C. K., Winter, A., Loukas, A., Tribolet, L., Gasser, R. B., and Hofmann, A. (2012) Hookworm SCP/TAPS protein structure - A key to understanding host-parasite interactions and developing new interventions. Biotechnol. Adv. 30, 652-657
83. O'Rourke, D., Baban, D., Demidova, M., Mott, R., and Hodgkin, J. (2006) Genomic clusters, putative pathogen recognition molecules, and antimicrobial genes are induced by infection of C. elegans with M. nematophilum. Genome Res. 16, 1005-1016
84. Ookuma, S., Fukuda, M., and Nishida, E. (2003) Identification of a DAF-16 transcriptional target gene, scl-1, that regulates longevity and stress resistance in Caenorhabditis elegans. Curr. Biol. 13, 427-431
85. Wang, J., and Kim, S. K. (2003) Global analysis of dauer gene expression in Caenorhabditis elegans. Development 130, 1621-1634
86. Navarro, S., Ferreira, I., and Loukas, A. (2013) The hookworm pharmacopoeia for inflammatory diseases. Int. J. Parasitol. 43, 225-231