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Proteases from Protozoa and Their Role in Infection

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Proteases in Physiology and Pathology

Abstract

One of the major classes of virulence factors acting in different host-pathogen interaction systems is comprised of proteases. Pathogen-secreted or membrane-associated proteases could be found to participate in different stages of establishment of infection. They are explored as candidate drug targets due to their key participation in the disease development process carried out by the pathogen. In this chapter we present an extensive review of the proteases of different protozoan parasites. Throughout the article we have made an effort to provide a comprehensive list of different proteases from various parasitic protozoa that have been demonstrated to execute major functions in the respective infection processes. Attempts have also been made to present their mode of action with respect to host invasion and disease development.

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References

  1. Klemba M, Goldberg DE (2002) Biological roles of proteases in parasitic protozoa. Annu Rev Biochem 71:275–305

    Article  CAS  PubMed  Google Scholar 

  2. Mottram JC, Brooks DR, Coombs GH (1998) Roles of cysteine proteinases of trypanosomes and Leishmania in host-parasite interactions. Curr Opin Microbiol 1:455–460

    Article  CAS  PubMed  Google Scholar 

  3. Sajid M, McKerrow JH (2002) Cysteine proteases of parasitic organisms (2002). Mol Biochem Parasitol 121:159–159

    Article  CAS  Google Scholar 

  4. McKerrow JH, Engel JC, Caffrey CR (1999) Cysteine protease inhibitors as chemotherapy for parasitic infections. Bioorg Med Chem 7:639–644

    Article  CAS  PubMed  Google Scholar 

  5. Wu YM, Wang XY, Liu X, Wang YF (2003) Data-mining approaches reveal hidden families of proteases in the genome of malaria parasite. Genome Res 13:601–616

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Shenai BR, Rosenthal PJ (2002) Reducing requirements for hemoglobin hydrolysis by Plasmodium falciparum cysteine proteases. Mol Biochem Parasitol 122:99–104

    Article  CAS  PubMed  Google Scholar 

  7. Malhotra P, Dasaradhi PV, Kumar A, Mohmmed A, Agrawal N, Bhatnagar RK, Chauhan VS (2002) Double-stranded RNA-mediated gene silencing of cysteine proteases (falcipain-1 and -2) of Plasmodium falciparum. Mol Microbiol 45:1245–1254

    Article  CAS  PubMed  Google Scholar 

  8. Francis SE, Sullivan DJ, Goldberg DE (1997) Hemoglobin metabolism in the malaria parasite Plasmodium falciparum. Annu Rev Microbiol 51:97–123

    Article  CAS  PubMed  Google Scholar 

  9. Pandey KC, Dixit R (2012) Structure-function of falcipains: malarial cysteine proteases. Journal of Tropical Medicine 2012:345195

    Article  PubMed  PubMed Central  Google Scholar 

  10. Rosenthal PJ, Sijwali PS, Singh A, Shenai BR (2002) Cysteine proteases of malaria parasites: targets for chemotherapy. Curr Pharm Des 8:1659–1672

    Article  CAS  PubMed  Google Scholar 

  11. Dalal S, Klemba M (2007) Roles for two aminopeptidases in vacuolar hemoglobin catabolism in Plasmodium falciparum. J Biol Chem 282:35978–35987

    Article  CAS  PubMed  Google Scholar 

  12. Klemba M, Gluzman I, Goldberg DE (2004) A Plasmodium falciparum dipeptidylaminopeptidase I participates in vacuolar hemoglobin degradation. J Biol Chem 279:43000–43007

    Article  CAS  PubMed  Google Scholar 

  13. Tanaka TQ, Deu E, Molina-Cruz A, Ashburne MJ, Ali O, Suri A, Kortagere S, Bogyo M, Williamsona KC (2013) Plasmodium Dipeptidyl Aminopeptidases as malaria transmission-blocking drug targets. Antimicrob Agents Chemother 57:4645–4652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Arastu-Kapur S, Ponder EL, Fonovic UP, Yeoh S, Yuan F, Fonovic M, Grainger M, Phillips CI, Powers JC, Bogyo M (2008) Identification of proteases that regulate erythrocyte rupture by the malaria parasite Plasmodium falciparum. Nat Chem Biol 4:203–213

    Article  CAS  PubMed  Google Scholar 

  15. Russo I, Oksman A, Vaupel B, Goldberg DE (2009) A calpain unique to alveolates is essential in Plasmodium falciparum and its knockdown reveals an involvement in pre-S-phase development. Proc Natl Acad Sci U S A 106:1554–1559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Le Roch KG, Zhou Y, Blair PL, Grainger M, Moch JK, Haynes JD, De La Vega P, Holder AA, Batalov S, Carucci DJ, Winzeler EA (2003) Discovery of gene function by expression profiling of the malaria parasite life cycle. Science 301:1503–1508

    Article  PubMed  Google Scholar 

  17. Bozdech Z, Llinas M, Pulliam BL, Wong ED, Zhu J, DeRisi JL (2003) The transcriptome of the intraerythrocytic developmental cycle of Plasmodium falciparum. PLoS Biol 1:E5

    Article  PubMed  PubMed Central  Google Scholar 

  18. Yeoh S, O'Donnell RA, Koussis K, Dluzewski AR, Ansell KH, Osborne SA, Hackett F, Withers-Martinez C, Mitchell GH, Bannister LH, Bryans JS, Kettleborough CA, Blackman MJ (2007) Subcellular discharge of a serine protease mediates release of invasive malaria parasites from host erythrocytes. Cell 131:1072–1083

    Article  CAS  PubMed  Google Scholar 

  19. McCoubrie JE, Miller SK, Sargeant T, Good RT, Hodder AN, Speed TP, de Koning-Ward TF, Crabb BS (2007) Evidence for a common role for the serine-type Plasmodium falciparum serine repeat antigen proteases: implications for vaccine and drug design. Infect Immun 75:5565–5574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Tillack M, Biller L, Irmer H, Freitas M, Gomes MA, Tannich E, Bruchhaus I (2007) The Entamoeba histolytica genome: primary structure and expression of proteolytic enzymes. BMC Genomics 8:170

    Article  PubMed  PubMed Central  Google Scholar 

  21. Gadasi H, Kobiler D (1983) Entamoeba histolytica: correlation between virulence and content of proteolytic enzymes. Exp Parasitol 55:105–110

    Article  CAS  PubMed  Google Scholar 

  22. Chadee K, Ndarathi C, Keller K (1990) Binding of proteolytically-degraded human colonic mucin glycoproteins to the gal/GalNAc adherence lectin of Entamoeba histolytica. Gut 31:890–895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. McCoy JJ, Mann BJ, Petri WA Jr (1994) Adherence and cytotoxicity of Entamoeba histolytica or how lectins let parasites stick around. Infect Immun 62:3045–3050

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Ragland BD, Ashley LS, Vaux DL, Petri WA Jr (1994) Entamoeba histolytica: target cells killed by trophozoites undergo DNA fragmentation which is not blocked by Bcl-2. Exp Parasitol 79:460–467

    Article  CAS  PubMed  Google Scholar 

  25. Huston CD, Boettner DR, Miller-Sims V, Petri WA Jr (2003) Apoptotic killing and phagocytosis of host cells by the parasite Entamoeba histolytica. Infect Immun 71:964–972

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Berninghausen O, Leippe M (1997) Necrosis versus apoptosis as the mechanism of target cell death induced by Entamoeba histolytica. Infect Immun 65:3615–3621

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Moncada D, Keller K, Chadee K (2003) Entamoeba histolytica Cysteine proteinases disrupt the polymeric structure of colonic mucin and alter its protective function. Infect Immun 71:838–844

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Moncada D, Keller K, Ankri S, Mirelman D, Chadee K (2006) Antisense inhibition of Entamoeba histolytica cysteine proteases inhibits colonic mucus degradation. Gastroenterology 130:721–730

    Article  CAS  PubMed  Google Scholar 

  29. Thibeaux R, Dufour A, Roux P, Bernier M, Baglin AC, Frileux P, Olivo-Marin JC, Guillen N, Labruyere E (2012) Newly visualized fibrillar collagen scaffolds dictate Entamoeba histolytica invasion route in the human colon. Cell Microbiol 14:609–621

    Article  CAS  PubMed  Google Scholar 

  30. Hou Y, Mortimer L, Chadee K (2010) Entamoeba histolytica Cysteine proteinase 5 binds integrin on colonic cells and stimulates NFkappaB-mediated pro-inflammatory responses. J Biol Chem 285:35497–35504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Thibeaux R, Ave P, Bernier M, Morcelet M, Frileux P, Guillen N, Labruyere E (2014) The parasite Entamoeba histolytica exploits the activities of human matrix metalloproteinases to invade colonic tissue. Nat Commun 5:5142

    Article  CAS  PubMed  Google Scholar 

  32. Bansal D, Ave P, Kerneis S, Frileux P, Boche O, Baglin AC, Dubost G, Leguern AS, Prevost MC, Bracha R, Mirelman D, Guillen N, Labruyere E (2009) An ex-vivo human intestinal model to study Entamoeba histolytica pathogenesis. PLoS Negl Trop Dis 3:e551

    Article  PubMed  PubMed Central  Google Scholar 

  33. Matthiesen J, Bar AK, Bartels AK, Marien D, Ofori S, Biller L, Tannich E, Lotter H, Bruchhaus I (2013) Overexpression of specific cysteine peptidases confers pathogenicity to a non-pathogenic Entamoeba histolytica clone. MBio 4:e00072–e00013

    Article  PubMed  PubMed Central  Google Scholar 

  34. Garcia-Rivera G, Rodriguez MA, Ocadiz R, Martinez-Lopez MC, Arroyo R, Gonzalez-Robles A, Orozco E (1999) Entamoeba histolytica: a novel cysteine protease and an adhesin form the 112kDa surface protein. Mol Microbiol 33:556–568

    Article  CAS  PubMed  Google Scholar 

  35. Ocadiz R, Orozco E, Carrillo E, Quintas LI, Ortega-Lopez J, Garcia-Perez RM, Sanchez T, Castillo-Juarez BA, Garcia-Rivera G, Rodriguez MA (2005) EhCP112 is an Entamoeba histolytica secreted cysteine protease that may be involved in the parasite-virulence. Cell Microbiol 7:221–232

    Article  CAS  PubMed  Google Scholar 

  36. Quintas-Granados LI, Orozco E, Brieba LG, Arroyo R, Ortega-Lopez J (2009) Purification, refolding and autoactivation of the recombinant cysteine proteinase EhCP112 from Entamoeba histolytica. Protein Expr Purif 63:26–32

    Article  CAS  PubMed  Google Scholar 

  37. Ocadiz-Ruiz R, Fonseca W, Martinez MB, Ocadiz-Quintanar R, Orozco E, Rodriguez MA (2013) Effect of the silencing of the Ehcp112 gene on the in vitro virulence of Entamoeba histolytica. Parasit Vectors 6:248–256

    Google Scholar 

  38. Ivens AC, Peacock CS, Worthey EA, Murphy L, Aggarwal G, Berriman M, Sisk E, Rajandream MA, Adlem E, Aert R, Anupama A, Apostolou Z, Attipoe P, Bason N, Bauser C, Beck A, Beverley SM, Bianchettin G, Borzym K, Bothe G, Bruschi CV, Collins M, Cadag E, Ciarloni L, Clayton C, Coulson RMR, Cronin A, Cruz AK, Davies RM, De Gaudenzi J, Dobson DE, Duesterhoeft A, Fazelina G, Fosker N, Frasch AC, Fraser A, Fuchs M, Gabel C, Goble A, Goffeau A, Harris D, Hertz-Fowler C, Hilbert H, Horn D, Huang YT, Klages S, Knights A, Kube M, Larke N, Litvin L, Lord A, Louie T, Marra M, Masuy D, Matthews K, Michaeli S, Mottram JC, Muller-Auer S, Munden H, Nelson S, Norbertczak H, Oliver K, O'Neil S, Pentony M, Pohl TM, Price C, Purnelle B, Quail MA, Rabbinowitsch E, Reinhardt R, Rieger M, Rinta J, Robben J, Robertson L, Ruiz JC, Rutter S, Saunders D, Schafer M, Schein J, Schwartz DC, Seeger K, Seyler A, Sharp S, Shin H, Sivam D, Squares R, Squares S, Tosato V, Vogt C, Volckaert G, Wambutt R, Warren T, Wedler H, Woodward J, Zhou SG, Zimmermann W, Smith DF, Blackwell JM, Stuart KD, Barrell B, Myler PJ (2005) The genome of the kinetoplastid parasite, Leishmania major. Science 309:436–442

    Article  PubMed  PubMed Central  Google Scholar 

  39. Rafati S, Salmanian AH, Hashemi K, Schaff C, Belli S, Fasel N (2001) Identification of Leishmania major cysteine proteinases as targets of the immune response in humans. Mol Biochem Parasitol 113:35–43

    Article  CAS  PubMed  Google Scholar 

  40. Mottram JC, Souza AE, Hutchison JE, Carter R, Frame MJ, Coombs GH (1996) Evidence from disruption of the lmcpb gene array of Leishmania mexicana that cysteine proteinases are virulence factors. Proc Natl Acad Sci U S A 93:6008–6013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Barralnetto M, Barral A, Brownell CE, Skeiky YAW, Ellingsworth LR, Twardzik DR, Reed SG (1992) Transforming growth-factor-Beta in Leishmanial infection - a parasite escape mechanism. Science 257:545–548

    Article  CAS  Google Scholar 

  42. Wilson ME, Young BM, Davidson BL, Mente KA, McGowan SE (1998) The importance of TGF-beta in murine visceral leishmaniasis. J Immunol 161:6148–6155

    CAS  PubMed  Google Scholar 

  43. Somanna A, Mundodi V, Gedamu L (2002) Functional analysis of cathepsin B-like cysteine proteases from Leishmania donovani complex - evidence for the activation of latent transforming growth factor beta. J Biol Chem 277:25305–25312

    Article  CAS  PubMed  Google Scholar 

  44. de Sousa LRF, Wu HM, Nebo L, Fernandes JB, da Silva MFDF, Kiefer W, Schirmeister T, Vieira PC (2015) Natural products as inhibitors of recombinant cathepsin L of Leishmania mexicana. Exp Parasitol 156:42–48

    Article  PubMed  Google Scholar 

  45. Schad C, Baum U, Frank B, Dietzel U, Mattern F, Gomes C, Ponte-Sucre A, Moll H, Schurigt U, Schirmeister T (2016) Development of a new Antileishmanial Aziridine-2,3-Dicarboxylate-based inhibitor with high selectivity for parasite cysteine proteases. Antimicrob Agents Chemother 60:797–805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Page MJ, Di Cera E (2008) Serine peptidases: classification, structure and function. Cell Mol Life Sci 65:1220–1236

    Article  CAS  PubMed  Google Scholar 

  47. Page MJ, Di Cera E (2008) Evolution of peptidase diversity. J Biol Chem 283:30010–30014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Alam A (2014) Serine proteases of malaria parasite Plasmodium falciparum: potential as antimalarial drug targets. Interdisciplinary Perspectives on Infectious Diseases 2014:453186

    Article  PubMed  PubMed Central  Google Scholar 

  49. Harris PK, Yeoh S, Dluzewski AR, O'Donnell RA, Withers-Martinez C, Hackett F, Bannister LH, Mitchell GH, Blackman MJ (2005) Molecular identification of a malaria merozoite surface sheddase. PLoS Pathog 1:241–251

    Article  CAS  PubMed  Google Scholar 

  50. Collins CR, Hackett F, Strath M, Penzo M, Withers-Martinez C, Baker DA, Blackman MJ (2013) Malaria parasite cGMP-dependent protein kinase regulates blood stage merozoite secretory organelle discharge and egress. PLoS Pathog 9:e1003344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Agarwal S, Singh MK, Garg S, Chitnis CE, Singh S (2013) Ca(2+) -mediated exocytosis of subtilisin-like protease 1: a key step in egress of Plasmodium falciparum merozoites. Cell Microbiol 15:910–921

    Article  CAS  PubMed  Google Scholar 

  52. Koussis K, Withers-Martinez C, Yeoh S, Child M, Hackett F, Knuepfer E, Juliano L, Woehlbier U, Bujard H, Blackman MJ (2009) A multifunctional serine protease primes the malaria parasite for red blood cell invasion. EMBO J 28:725–735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Silmon de Monerri NC, Flynn HR, Campos MG, Hackett F, Koussis K, Withers-Martinez C, Skehel JM, Blackman MJ (2011) Global identification of multiple substrates for Plasmodium falciparum SUB1, an essential malarial processing protease. Infect Immun 79:1086–1097

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Child MA, Epp C, Bujard H, Blackman MJ (2010) Regulated maturation of malaria merozoite surface protein-1 is essential for parasite growth. Mol Microbiol 78:187–202

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Barale JC, Blisnick T, Fujioka H, Alzari PM, Aikawa M, Braun-Breton C, Langsley G (1999) Plasmodium falciparum subtilisin-like protease 2, a merozoite candidate for the merozoite surface protein 1-42 maturase. Proc Natl Acad Sci U S A 96:6445–6450

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Child MA, Harris PK, Collins CR, Withers-Martinez C, Yeoh S, Blackman MJ (2013) Molecular determinants for subcellular trafficking of the malarial sheddase PfSUB2. Traffic 14:1053–1064

    Article  CAS  PubMed  Google Scholar 

  57. Alam A, Bhatnagar RK, Chauhan VS (2012) Expression and characterization of catalytic domain of Plasmodium falciparum subtilisin-like protease 3. Mol Biochem Parasitol 183:84–89

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Alam A, Bhatnagar RK, Relan U, Mukherjee P, Chauhan VS (2013) Proteolytic activity of Plasmodium falciparum subtilisin-like protease 3 on parasite profilin, a multifunctional protein. Mol Biochem Parasitol 191:58–62

    Article  CAS  PubMed  Google Scholar 

  59. Dowse TJ, Pascall JC, Brown KD, Soldati D (2005) Apicomplexan rhomboids have a potential role in microneme protein cleavage during host cell invasion. Int J Parasitol 35:747–756

    Article  CAS  PubMed  Google Scholar 

  60. O'Donnell RA, Hackett F, Howell SA, Treeck M, Struck N, Krnajski Z, Withers-Martinez C, Gilberger TW, Blackman MJ (2006) Intramembrane proteolysis mediates shedding of a key adhesin during erythrocyte invasion by the malaria parasite. J Cell Biol 174:1023–1033

    Article  PubMed  PubMed Central  Google Scholar 

  61. Baker RP, Wijetilaka R, Urban S (2006) Two plasmodium rhomboid proteases preferentially cleave different adhesins implicated in all invasive stages of malaria. PLoS Pathog 2:922–932

    Article  CAS  Google Scholar 

  62. Vera IM, Beatty WL, Sinnis P, Kim K (2011) Plasmodium protease ROM1 is important for proper formation of the Parasitophorous vacuole. PLoS Pathog 7:e1002197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Lin JW, Meireles P, Prudencio M, Engelmann S, Annoura T, Sajid M, Chevalley-Maurel S, Ramesar J, Nahar C, Avramut CMC, Koster AJ, Matuschewski K, Waters AP, Janse CJ, Mair GR, Khan SM (2013) Loss-of-function analyses defines vital and redundant functions of the plasmodium rhomboid protease family. Mol Microbiol 88:318–338

    Article  CAS  PubMed  Google Scholar 

  64. Kim K (2004) Role of proteases in host cell invasion by Toxoplasma gondii and other Apicomplexa. Acta Trop 91:69–81

    Article  CAS  PubMed  Google Scholar 

  65. Miller SA, Binder EM, Blackman MJ, Carruthers VB, Kim K (2001) A conserved subtilisin-like protein TgSUB1 in microneme organelles of Toxoplasma gondii. J Biol Chem 276:45341–45348

    Article  CAS  PubMed  Google Scholar 

  66. Lagal V, Binder EM, Huynh MH, Kafsack BFC, Harris PK, Diez R, Chen D, Cole RN, Carruthers VB, Kim K (2010) Toxoplasma gondii protease TgSUB1 is required for cell surface processing of micronemal adhesive complexes and efficient adhesion of tachyzoites. Cell Microbiol 12:1792–1808

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Miller SA, Thathy V, Ajioka JW, Blackman MJ, Kim K (2003) TgSUB2 is a Toxoplasma gondii rhoptry organelle processing proteinase. Mol Microbiol 49:883–894

    Article  CAS  PubMed  Google Scholar 

  68. Brossier F, Jewett TJ, Sibley LD, Urban S (2005) A spatially localized rhomboid protease cleaves cell surface adhesins essential for invasion by Toxoplasma. Proc Natl Acad Sci U S A 102:4146–4151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Brossier F, Starnes GL, Beatty WL, Sibley LD (2008) Microneme rhomboid protease TgROM1 is required for efficient intracellular growth of Toxoplasma gondii. Eukaryot Cell 7:664–674

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Buguliskis JS, Brossier F, Shuman J, Sibley LD (2010) Rhomboid 4 (ROM4) affects the processing of surface Adhesins and facilitates host cell invasion by Toxoplasma gondii. PLoS Pathog 6:e1000858

    Article  PubMed  PubMed Central  Google Scholar 

  71. Shen B, Buguliskis JS, Lee TD, Sibley LD (2014) Functional analysis of rhomboid proteases during Toxoplasma invasion. MBio 5:e01795–e01714

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Rodriguez A, Samoff E, Rioult MG, Chung A, Andrews NW (1996) Host cell invasion by trypanosomes requires lysosomes and microtubule/kinesin-mediated transport. J Cell Biol 134:349–362

    Article  CAS  PubMed  Google Scholar 

  73. Rodriguez A, Rioult MG, Ora A, Andrews NW (1995) A trypanosome-soluble factor induces Ip3 formation, intracellular Ca2+ mobilization and microfilament rearrangement in host-cells. J Cell Biol 129:1263–1273

    Article  CAS  PubMed  Google Scholar 

  74. Caler EV, de Avalos SV, Haynes PA, Andrews NW, Burleigh BA (1998) Oligopeptidase B-dependent signaling mediates host cell invasion by Trypanosoma cruzi. EMBO J 17:4975–4986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Morty RE, Lonsdale-Eccles JD, Morehead J, Caler EV, Mentele R, Auerswald EA, Coetzer THT, Andrews NW, Burleigh BA (1999) Oligopeptidase B from Trypanosoma brucei, a new member of an emerging subgroup of serine oligopeptidases. J Biol Chem 274:26149–26156

    Article  CAS  PubMed  Google Scholar 

  76. da Silva-Lopeza RE, Morgado-Diaz JA, dos Santos PT, Giovanni-De-Simone S (2008) Purification and subcellular localization of a secreted 75 kDa Trypanosoma cruzi serine oligopeptidase. Acta Trop 107:159–167

    Article  Google Scholar 

  77. Moss CX, Brown E, Hamilton A, Van der Veken P, Augustyns K, Mottram JC (2015) An essential signal peptide peptidase identified in an RNAi screen of serine peptidases of Trypanosoma brucei. PLoS One 10:e0123241

    Article  PubMed  PubMed Central  Google Scholar 

  78. Baxt LA, Baker RP, Singh U, Urban S (2008) An Entamoeba histolytica rhomboid protease with atypical specificity cleaves a surface lectin involved in phagocytosis and immune evasion. Genes Dev 22:1636–1646

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Baxt LA, Rastew E, Bracha R, Mirelman D, Singh U (2010) Downregulation of an Entamoeba histolytica rhomboid protease reveals roles in regulating parasite adhesion and phagocytosis. Eukaryot Cell 9:1283–1293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Rastew E, Morf L, Singh U (2015) Entamoeba histolytica Rhomboid protease 1 has a role in migration and motility as validated by two independent genetic approaches. Exp Parasitol 154:33–42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Klemba M, Beatty W, Gluzman I, Goldberg DE (2004) Trafficking of plasmepsin II to the food vacuole of the malaria parasite Plasmodium falciparum. J Cell Biol 164:47–56

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Russo I, Babbitt S, Muralidharan V, Butler T, Oksman A, Goldberg DE (2010) Plasmepsin V licenses Plasmodium proteins for export into the host erythrocyte. Nature 463:632–636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Horrocks P, Muhia D (2005) Pexel/VTS: a protein-export motif in erythrocytes infected with malaria parasites. Trends Parasitol 21:396–399

    Article  CAS  PubMed  Google Scholar 

  84. Silva AM, Lee AY, Gulnik SV, Majer P, Collins J, Bhat TN, Collins PJ, Cachau RE, Luker KE, Gluzman IY, Francis SE, Oksman A, Goldberg DE, Erickson JW (1996) Structure and inhibition of plasmepsin II, a hemoglobin-degrading enzyme from Plasmodium falciparum. Proc Natl Acad Sci U S A 93:10034–10039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Nezami A, Kimura T, Hidaka K, Kiso A, Liu J, Kiso Y, Goldberg DE, Freire E (2003) High-affinity inhibition of a family of Plasmodium falciparum proteases by a designed adaptive inhibitor. Biochemistry 42:8459–8464

    Article  CAS  PubMed  Google Scholar 

  86. Coombs GH, Goldberg DE, Klemba M, Berry C, Kay J, Mottram JC (2001) Aspartic proteases of Plasmodium falciparum and other parasitic protozoa as drug targets. Trends Parasitol 17:532–537

    Article  CAS  PubMed  Google Scholar 

  87. McKerrow JH, Rosenthal PJ, Swenerton R, Doyle P (2008) Development of protease inhibitors for protozoan infections. Curr Opin Infect Dis 21:668–672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

A.G. acknowledges the financial support of the Dept. of Science and Technology, Govt. of India, for DST INSPIRE faculty fellowship.

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Authors and Affiliations

  1. Division of Plant Biology, Bose Institute, Centenary Campus, Kolkata, 700054, India

    Anupama Ghosh

  2. Integrated Science Education and Research Center and Department of Biotechnology, Visva Bharati University, Shantiniketan, 731235, India

    Sanghamitra Raha

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  1. Anupama Ghosh
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  2. Sanghamitra Raha
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Correspondence to Anupama Ghosh or Sanghamitra Raha .

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Editors and Affiliations

  1. Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India

    Sajal Chakraborti

  2. St. Boniface Hospital Research Centre, University of Manitoba, Faculty of Health Sciences, College of Medicine, Institute of Cardiovascular Sciences, Manitoba, Winnipeg, Canada

    Naranjan S. Dhalla

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Ghosh, A., Raha, S. (2017). Proteases from Protozoa and Their Role in Infection. In: Chakraborti, S., Dhalla, N. (eds) Proteases in Physiology and Pathology. Springer, Singapore. https://doi.org/10.1007/978-981-10-2513-6_8

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