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Article Number - 19EC4499816


Vol.5(1), pp. 6-14 , April 2013
DOI: 10.5897/JCBBR12.013
ISSN: 2141-2227



Full Length Research Paper

Annotation of virulence factors in schistosomes for the development of a SchistoVir database


Adewale S. Adebayo1 and Chiaka I. Anumudu2*




1Cell Biology and Genetics Unit, Department of Zoology, University of Ibadan, Oyo State, Nigeria

2Cellular Parasitology Programme, Department of Zoology, University of Ibadan, Oyo State, Nigeria.


Email: chiaka.anumudu@mail.ui.edu.ng, walsaks002@yahoo.com






 Accepted: 08 March 2013  Published: 30 April 2013

Copyright © 2013 Author(s) retain the copyright of this article.
This article is published under the terms of the Creative Commons Attribution License 4.0


Scientific efforts in the eradication of neglected tropical diseases, such as those caused by the parasitic helminthes, can be improved if a database of key virulence factors directly implicated in pathogenesis is available. As a first step towards creating SchistoVir, a database of virulence protein factors in schistosomes, in this study, we curated, annotated and aligned sequences of twenty virulence factors identified from the literature, using several bioinformatics tools including UniProtKB, SchistoDB, VirulentPred, InterProScan, ProtScale, MotifScan, TDRtarget, SignalP, MODBASE, PDB and MUSCLE. Among the protein entries, the most frequently occurring amino acid residues were lysine, serine, leucine, glutamine, glycine and cysteine in order of magnitude. Although sequence repeat regions (SRRs) of significant value were identified manually in fifty percent of the proteins (while dipeptide repeats (DiPs) and single amino acid repeats (SAARs) were not), nevertheless, seventy-two percent of the protein entries were classified as virulent by the prediction model, VirulentPred. Most of the entries (eighty percent) did not have target compounds based on the database of available chemical compounds at TDRtargets. Fourteen of the twenty entries (seventy percent) had more than 30 consecutively negative amino acid residues based on the ProtScale’s Kyte and Doolittle hydrophobicity plot. Hence, they would be hydrophobic enough to be transmembrane in location or secretory in nature. Only 7 (tyrosinase, serine protease1, Tspan-1, VAL4, cathepsin b and L and calreticulin) had cleavage sites and signal peptides, while none had a significant signal anchor probability. The annotations and characterization provided by this work and the development of a SchistoVir database will aid in further research of schistosome pathogenesis and control.

 

Key words: Protein database, bioinformatics tools, virulence proteins/factors, annotation, schistosomes.

Aslam A, Quinn P, McIntosh RS, Shi J, Ghumra A, McKerrow JH, Bunting KA, Dunne DW, Doenhoff MJ, Sherie LM, Ke Z, Richard JP (2008). Proteases from Schistosoma mansoni cercariae cleave IgE at solvent exposed interdomain region. Mol. Immunol. 45(2):567-574.
http://dx.doi.org/10.1016/j.molimm.2007.05.021
PMid:17631966
 
Bendtsen JD, Nielsen H, von Heijne G, Brunak S (2004). Improved prediction of signal peptides: SignalP 3.0. J. Mol. Biol. 340:783-795.
http://dx.doi.org/10.1016/j.jmb.2004.05.028
PMid:15223320
 
Berriman M, Haas BJ,LoVerdo PT, Wilson RA, Dillon GP, Cerquiera GC, El Sayed NM (2009). The genome of the blood fluke Schistosoma mansoni. Nature 460:352-358
http://dx.doi.org/10.1038/nature08160
PMid:19606141 PMCid:PMC2756445
 
Bos DH, Mayfield C, Minchella DJ (2009). Analysis of regulatory protease sequences identified through bioinformatic data mining of the Schistosoma mansoni genome. BMC Genomics 10: 488-492.
http://dx.doi.org/10.1186/1471-2164-10-488
PMid:19845954 PMCid:PMC2772863
 
Boumis G, Angelucci F, Bellelli A, Brunori M, Dimastrogiovanni D, Miele AE (2011). Structural and functional characterization of Schistosoma mansoni Thioredoxin. Protein Sci. 20(6):1069-1076.
http://dx.doi.org/10.1002/pro.634
PMid:21465612 PMCid:PMC3104236
 
Blanco MT, Sacristán B, Lucio L, Blanco J, Pérez-Giraldo C, Gómez-García AC (2010). Cell surface hydrophobicity as an indicator of other virulence factors in Candida albicans. Rev. Iberoam Micol. 27(4):195-199.
http://dx.doi.org/10.1016/j.riam.2010.09.001
PMid:20849975
 
Braschi S, Borges WC, Wilson RA (2006). Proteomic analysis of the schistosome tegument and its surface membranes. Mem Inst Oswaldo Cruz. 101(I): 205-212.
http://dx.doi.org/10.1590/S0074-02762006000900032
PMid:17308771
 
Caprona A, Riveaua G, Caprona M, Trottein F (2005). Schistosomes: the road from host–parasite interactions to vaccines in clinical trials. Trends Parasitol. 21(3): 143-149.
http://dx.doi.org/10.1016/j.pt.2005.01.003
PMid:15734662
 
Cardoso FC, Macedo GC, Gava E, Kitten GT, Mati VL (2008). Schistosoma mansoni Tegument Protein Sm29 Is Able to Induce a Th1-Type of Immune Response and Protection against Parasite Infection. PLoS Negl Trop Dis. 2(10): e308.
http://dx.doi.org/10.1371/journal.pntd.0000308
PMid:18827884 PMCid:PMC2553283
 
Chalmers IW, McArdle AJ, Coulson RM, Wagner MA, Schmid R, Hirai H, Hoffmann KF (2008). Developmentally regulated expression, alternative splicing and distinct sub-groupings in members of the Schistosoma mansoni venom allergen-like (SmVAL) gene family. BMC Genomics 9:89.
http://dx.doi.org/10.1186/1471-2164-9-89
PMid:18294395 PMCid:PMC2270263
 
Crowther GJ, Shanmugam D, Carmona SJ, Doyle MA, Hertz-Fowler C, Berriman M, Nwaka S, Ralph SA, Roos DS, Van Voorhis WC, Agüero F (2010). Identification of Attractive Drug Targets in Neglected-Disease Pathogens Using an In Silico Approach. PLoS Negl Trop Dis. 4(8): e804.
http://dx.doi.org/10.1371/journal.pntd.0000804
PMid:20808766 PMCid:PMC2927427
 
Curwen RS, Ashton PD, Sundaralingam S, and Wilson RA (2006). Identification of Novel Proteases and Immunomodulators in the Secretions of Schistosome Cercariae That Facilitate Host Entry. Mol. Cell. Proteomics 5(5):835-844.
http://dx.doi.org/10.1074/mcp.M500313-MCP200
PMid:16469760
 
Dalton JP, Clough FA, Jones MK, Brindley PJ (1997). The cysteine proteinases of Schistosoma mansoni cercariae. Parasitology 114: 105-112.
http://dx.doi.org/10.1017/S003118209600830X
PMid:9051919
 
Depledge DP, Lower RP, Smith DF (2007). RepSeq – A database of amino acid repeats present in lower eukaryotic pathogens. BMC Bioinformatics 8:122.
http://dx.doi.org/10.1186/1471-2105-8-122
PMid:17428323 PMCid:PMC1854910
 
Dvorak J, Mashiyama ST, Braschi S, Sajid M, Knudsen GM, Hansell E, Lim KC, Hsieh I, Bahgat M, Mackenzie B, Medzihradszky KF, Babbitt PC, Caffrey CF and McKerrow JH (2008). Differential use of protease families for invasion by schistosome cercariae. Biochimie 90: 345-358.
http://dx.doi.org/10.1016/j.biochi.2007.08.013
PMid:17936488
 
Edgar RC (2004). MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics 5:113.
http://dx.doi.org/10.1186/1471-2105-5-113
PMid:15318951 PMCid:PMC517706
 
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.
http://dx.doi.org/10.1038/nprot.2007.131
PMid:17446895
 
Fankhauser N, Nguyen-Ha T, Adler J, Mäse P (2007). Surface antigens and potential virulence factors from parasites detected by comparative genomics of perfect amino acid repeats. Proteome Sci. 5: 20.
http://dx.doi.org/10.1186/1477-5956-5-20
PMid:18096064 PMCid:PMC2254594
 
Fitzpatrick JM, Hirai YHH, Hoffmann KF (2007). Schistosome egg production is dependent upon the activities of two developmentally regulated tyrosinases. FASEB J. 21: 823-835.
http://dx.doi.org/10.1096/fj.06-7314com
PMid:17167065
 
Fumagalli M, Pozzoli U, Cagliani R, Comi GP, Bresolin N, Clerici M, Sironi M (2010). The landscape of human genes involved in the immune response to parasitic worms. BMC Evol. Biol. 10:264.
http://dx.doi.org/10.1186/1471-2148-10-264
PMid:20807397 PMCid:PMC2940816
 
Garg A, Gupta D (2008). VirulentPred: a SVM based prediction method for virulent proteins in bacterial pathogens. BMC Bioinformatics 9:62.
http://dx.doi.org/10.1186/1471-2105-9-62
PMid:18226234 PMCid:PMC2254373
 
Gomez C, Ramirez ME, Calixto-Galvez M, Medel O and Rodríguez MA (2010). Regulation of Gene Expression in Protozoa Parasites. J Biomed. Biotechnol. 2010: 726045.
http://dx.doi.org/10.1155/2010/726045
PMid:20204171 PMCid:PMC2830571
 
Gravekamp C, Rosner B, Madoff LC (1998). Deletion of repeats in the alpha C protein enhances the pathogenicity of group B streptococci in immune mice. Infect. Immun. 66:4347-4354.
PMid:9712787 PMCid:PMC108525
 
Guillou F, Roger E, Moné Y, Rognon A, Grunau C, Théron A, Mitta G, Coustau C, Gourbal BE (2007). Excretory–secretory proteome of larval Schistosoma mansoni and Echinostoma caproni, two parasites of Biomphalaria glabrata. Mol. Biochem. Parasitol. 155 (1):45-56.
http://dx.doi.org/10.1016/j.molbiopara.2007.05.009
PMid:17606306
 
Hansell E, Braschi S, Medzhiradszsky KF, Sajid M, Debnath M (2008). Proteomic Analysis of Skin invasion by blood fluke larvae. PLoS Negl. Trop. Dis. 2(7):e262.
http://dx.doi.org/10.1371/journal.pntd.0000262
PMid:18629379 PMCid:PMC2467291
 
Herve M, Angeli V, Pinzar E, Wintjens R, Faveeuw C, Narumiya S, Capron A (2003). Pivotal roles of the parasite PGD2 synthase and of the host D prostanoid receptor 1 in schistosome immune evasion. Eur. J. Immunol. 33: 2764–2772.
http://dx.doi.org/10.1002/eji.200324143
PMid:14515260
 
Hogeweg P (2011). The Roots of Bioinformatics in Theoretical Biology. PLoS Comput. Biol. 7(3): e1002021.
http://dx.doi.org/10.1371/journal.pcbi.1002021
PMid:21483479 PMCid:PMC3068925
 
Kalita MK, Ramasamy G, Duraisamy S, Chauhan VS and Gupta D (2006). ProtRepeatsDB: a database of amino acid repeats in genomes. BMC Bioinformatics (database) 7:336.
http://dx.doi.org/10.1186/1471-2105-7-336
PMid:16827924 PMCid:PMC1538635
 
Kane CM, Cervi L, Sun J, McKee AS, Katherine SM, Sagi S, Christopher AH, Edward JP (2004). Helminth Antigens Modulate TLR-Initiated Dendritic Cell Activation. J. Immunol. 173(12):7454-61.
PMid:15585871
 
Karlin S, Brocchieri L, Bergman A, Mrazek J, Gentles AJ (2002). Amino acid runs in eukaryotic proteomes, disease associations. Proc. Natl. Acad. Sci. USA 99:333-338.
http://dx.doi.org/10.1073/pnas.012608599
PMid:11782551 PMCid:PMC117561
 
Katsir LE, Schilmiller AL, Staswick PE, He SY, Howe GA (2008). COI1 is a critical component of a receptor for jasmonate and the bacterial virulence factor coronatine. Proc. Natl. Acad. Sci. 105(19): 7100-7105
http://dx.doi.org/10.1073/pnas.0802332105
PMid:18458331 PMCid:PMC2383947
 
Kim KH, Willger SD, Park SW, Puttikamonkul S, Grahl N (2009). TmpL, a Transmembrane Protein Required for Intracellular Redox Homeostasis and Virulence in a Plant and an Animal Fungal Pathogen. PLoS Pathog 5(11): e1000653.
http://dx.doi.org/10.1371/journal.ppat.1000653
PMid:19893627 PMCid:PMC2766074
 
Lin YL, He S (2006). Sm22.6 antigen is an inhibitor to human thrombin. Mol. Biochem. Parasitol. 147(1):95-100.
http://dx.doi.org/10.1016/j.molbiopara.2006.01.012
PMid:16499980
 
Lopez Quezada LA, McKerrow JH (2011). Schistosome serine protease inhibitors: parasite defense or homeostasis. Anais da Academia Brasileira de Ciências (Annals of the Brazilian Academy of Sciences) 83(2): 663-672.
http://dx.doi.org/10.1590/S0001-37652011000200025
 
MacDonald AS, Araujo MI, Pearce EJ (2002). Immunology of Parasitic Helminth Infections. Infect. Immun. 70(2):427–433.
http://dx.doi.org/10.1128/IAI.70.6.2796-2804.2002
http://dx.doi.org/10.1128/IAI.70.2.427-433.2002
 
Matisz CE, McDougall JJ, Sharkey KA, McKay DM (2011). Helminth Parasites and the Modulation of Joint Inflammation. J. Parasitol. Res. 2011:942616.
http://dx.doi.org/10.1155/2011/942616
PMid:21584243 PMCid:PMC3092582
 
Mulder NJ, Apweiler R, Attwood TK, Bairoch A, Bateman A, Binns D, Bork P, Buillard V, Cerutti L (2007). New developments in the InterPro database. Nucleic Acids Res. 35: D224-D228.
http://dx.doi.org/10.1093/nar/gkl841
PMid:17202162 PMCid:PMC1899100
 
Nielsen H, Engelbrecht J, Brunak S and von Heijne G (1997). Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites. Protein Eng. 10:1-6.
http://dx.doi.org/10.1093/protein/10.1.1
PMid:9051728
 
Pieper U, Webb BM, Barkan DT, Schneidman-Duhovny D, Schlessinger A, Braberg H et al (2011). MODBASE, a database of annotated comparative protein structure models and associated resources. Nucleic Acids Res. 39:465-474.
http://dx.doi.org/10.1093/nar/gkq1091
PMid:21097780 PMCid:PMC3013688
 
Quezada CM, Hicks SW, Galán JE, Stebbins CE (2009). A family of Salmonella virulence factors functions as a distinct class of autoregulated E3 ubiquitin ligases. Proc. Natl. Acad. Sci. 106(12): 4864-4869.
http://dx.doi.org/10.1073/pnas.0811058106
PMid:19273841 PMCid:PMC2653562
 
Rabia I, El-Ahwany E, El-Komy W, Nagy F (2010). Immunomodulation of Hepatic Morbidity in Murine Schistosoma mansoni Using Fatty Acid Binding Protein. J. Am. Sci. 6(7):170-176.
 
Ramana J, Gupta D (2009). ProtVirDB: a database of protozoan virulent proteins. Bioinformatics 25 (12):1568-1569.
http://dx.doi.org/10.1093/bioinformatics/btp258
PMid:19369494
 
Ramos CR, Figueredo RC, Pertinhez TA, Vilar MM, Nascimento AL et al (2003). Gene structure and M20T polymorphism of the Schistosoma mansoni Sm14 fatty acid-binding protein: structural, functional and immunoprotection analysis. J. Biol. Chem. 278:12745-12751.
http://dx.doi.org/10.1074/jbc.M211268200
PMid:12551912
 
Ramos CR, Spisni A, Oyama S Jr, Sforca ML, Ramos HR, Vilar MM et al (2009). Stability Improvement of the fatty acid binding protein Sm14 from S mansoni by Cys rep: Structural and functional characterization of a vaccine candidate. J. Biochim. Biophys. Acta 1794(4):655-662.
http://dx.doi.org/10.1016/j.bbapap.2008.12.010
PMid:19150418
 
Reis EAG, Mauadi Carmo TA, Athanazio R, Reis MG, Harn DA Jr (2008). Schistosoma mansoni triose phosphate isomerase peptide MAP4 is able to trigger naıve donor immune response towards a type-1 cytokine profile. Scand. J. Immunol. (Clinical Immunology) 68:169–176.
http://dx.doi.org/10.1111/j.1365-3083.2008.02131.x
PMid:18565118
 
Sharma M, Khanna S, Bulusu G, Mitra A (2009). Comparative modeling of thioredoxin reductase from Schistosoma mansoni: a multifunctional target for antischistosomal therapy. J. Mol. Graph Model 27(6):665-675.
http://dx.doi.org/10.1016/j.jmgm.2008.10.009
PMid:19070522
 
Schulz GE, Vogt J (1999). The structure of the outer membrane protein OmpX from Escherichia coli reveals possible mechanisms of virulence. Structure 7 (10): 1301–1309.
http://dx.doi.org/10.1016/S0969-2126(00)80063-5
 
Sigrist CJA, Cerutti L, De Castro E, Langendijk-Genevaux PS, Bulliard V, Bairoch A, Hulo N (2010). PROSITE, a protein domain database for functional characterization and annotation. Nucleic Acids Res. (Database) 38: 161–166.
http://dx.doi.org/10.1093/nar/gkp885
PMid:19858104 PMCid:PMC2808866
 
Tsai CT, Huang WL, Ho SJ, Shu LS, Ho SY (2009). Virulent-GO: Prediction of Virulent Proteins in Bacterial Pathogens Utilizing Gene Ontology Terms. Int. J. Biol. Life Sci. 5(4):2009
 
Verjovski-Almeida S, DeMarco R (2008). Current developments on Schistosoma proteomics. Acta Tropica 108:183-185.
http://dx.doi.org/10.1016/j.actatropica.2008.04.017
PMid:18539255
 
World Health Organisation (WHO) Document (2010). Parasitic Diseases-Schistosomiasis. Available at http://who.int/vaccine_research/diseases/soa_parasitic/en/index5.html.Accessed 13 July 2011.
 
Zhou CE, Smith J, Lam M, Zemla A, Dyer MD, Slezak T (2007). MvirDB—a microbial database of protein toxins, virulence factors and antibiotic resistance genes for bio-defence applications. Nucleic Acids Res. (database) 35:391–394.
http://dx.doi.org/10.1093/nar/gkl791
PMid:17090593 PMCid:PMC1669772

 


APA (2013). Annotation of virulence factors in schistosomes for the development of a SchistoVir database. Journal of Computational Biology and Bioinformatics Research, 5(1), 6-14.
Chicago Adewale S. Adebayo and Chiaka I. Anumudu. "Annotation of virulence factors in schistosomes for the development of a SchistoVir database." Journal of Computational Biology and Bioinformatics Research 5, no. 1 (2013): 6-14.
MLA Adewale S. Adebayo and Chiaka I. Anumudu. "Annotation of virulence factors in schistosomes for the development of a SchistoVir database." Journal of Computational Biology and Bioinformatics Research 5.1 (2013): 6-14.
   
DOI 10.5897/JCBBR12.013
URL http://academicjournals.org/journal/JCBBR/article-abstract/19EC4499816

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