Skip to main content

Advertisement

SpringerLink
Log in

Bacterial staphylokinase as a promising third-generation drug in the treatment for vascular occlusion

  • Review
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Vascular occlusion is one of the major causes of mortality and morbidity. Blood vessel blockage can lead to thrombotic complications such as myocardial infarction, stroke, deep venous thrombosis, peripheral occlusive disease, and pulmonary embolism. Thrombolytic therapy currently aims to rectify this through the administration of recombinant tissue plasminogen activator. Research is underway to design an ideal thrombolytic drug with the lowest risk. Despite the potent clot lysis achievable using approved thrombolytic drugs such as alteplase, reteplase, streptokinase, tenecteplase, and some other fibrinolytic agents, there are some drawbacks, such as high production cost, systemic bleeding, intracranial hemorrhage, vessel re-occlusion by platelet-rich and retracted secondary clots, and non-fibrin specificity. In comparison, bacterial staphylokinase, is a new, small-size plasminogen activator, unlike bacterial streptokinase, it hinders the systemic degradation of fibrinogen and reduces the risk of severe hemorrhage. A fibrin-bound plasmin–staphylokinase complex shows high resistance to a2-antiplasmin-related inhibition. Staphylokinase has the potential to be considered as a promising thrombolytic agent with properties of cost-effective production and the least side effects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Notes

  1. The abbreviations used are: CVDs cardiovascular diseases, DVT deep venous thrombosis, t-PA tissue plasminogen activator, PAI-1 plasminogen activator inhibitor type 1, TIMI thrombolysis in myocardial infarction, ISIS international study of infarct survival, ASSENT assessment of safety and efficacy of a new thrombolytic agent, AMI acute myocardial infarction, AIS acute ischemic stroke, EGF epidermal growth factor, CHO chinese hamster ovary, DSPA desmodus salivary plasminogen activators, EACA epsilon-aminocaproic acid, LBS lysine binding site, FCB-2 fibrin(ogen) cyanogen bromide fragment-2, E (DD) complex of D-dimer non-covalently associated with fragment E, DD D-dimer, SAK staphylokinase, PEG poly ethylene glycol, CAPTORS collaborative angiographic patency trial of recombinant staphylokinase, ESPRIT european study of the prevention of reocclusion after initial thrombolysis.

References

  1. Periayah MH, Halim AS, Mat Saad AZ (2017) Mechanism action of platelets and crucial blood coagulation pathways in hemostasis. Int J Hematol Oncol Stem Cell Res. 11(4):319–327

    PubMed  PubMed Central  Google Scholar 

  2. Raskob GE, Angchaisuksiri P, Blanco AN, Buller H, Gallus A, Hunt BJ et al (2014) Thrombosis: a major contributor to global disease burden. Arterioscler Thromb Vasc Biol 34(11):2363–2371

    CAS  PubMed  Google Scholar 

  3. Nichols M, Townsend N, Scarborough P, Rayner M (2013) Cardiovascular disease in Europe: epidemiological update. Eur Heart J 34(39):3028–3034

    PubMed  Google Scholar 

  4. Kotra SR, Peravali B, Kumar A, Pulicherla K (2013) Staphylokinase: a boon in medical sciences–review. M J Pharm Med Sci 2(2):28–34

    Google Scholar 

  5. Alexander M (2013) Tobacco use and the risk of cardiovascular diseases in developed and developing countries. University of Cambridge, Cambridge

    Google Scholar 

  6. Pulicherla K, Kumar A, Gadupudi G, Kotra SR, Sambasiva Rao K (2013) In vitro characterization of a multifunctional staphylokinase variant with reduced reocclusion, produced from salt inducible E. coli GJ1158. BioMed Res Int 2013:297305

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Kowalski M, Brown G, Bieniasz M, Oszajca K, Chabielska E, Pietras T et al (2009) Cloning and expression of a new recombinant thrombolytic and anthithrombotic agent–a staphylokinase variant. Acta Biochim Pol 56(1):41

    CAS  PubMed  Google Scholar 

  8. Kikkert WJ, van Geloven N, van der Laan MH, Vis MM, Baan J, Koch KT et al (2014) The prognostic value of Bleeding Academic Research Consortium (BARC)-defined bleeding complications in ST-segment elevation myocardial infarction: a comparison with the TIMI (Thrombolysis In Myocardial Infarction), GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries), and ISTH (International Society on Thrombosis and Haemostasis) bleeding classifications. J Am Coll Cardiol 63(18):1866–1875

    PubMed  Google Scholar 

  9. Kumar A, Pulicherla K, Ram KS, Rao K (2010) Evolutionary trend of thrombolytics. Int J Bio-sci Bio-technol 2(4):51–68

  10. Ulbricht C (2012) Peripheral vascular disease: an integrative approach: a natural standard monograph. Altern Complement Ther 18(1):44–50

    Google Scholar 

  11. Deb P, Sharma S, Hassan K (2010) Pathophysiologic mechanisms of acute ischemic stroke: an overview with emphasis on therapeutic significance beyond thrombolysis. Pathophysiology 17(3):197–218

    CAS  Google Scholar 

  12. Wang J (2010) Preclinical and clinical research on inflammation after intracerebral hemorrhage. Prog Neurobiol 92(4):463–477

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Sikri N, Bardia A (2007) A history of streptokinase use in acute myocardial infarction. Tex Heart Inst J 34(3):318

    PubMed  PubMed Central  Google Scholar 

  14. Mueller RL, Scheidt S (1994) History of drugs for thrombotic disease. Discovery, development, and directions for the future. Circulation 89(1):432–449

    CAS  PubMed  Google Scholar 

  15. Kunamneni A, Ravuri BD, Saisha V, Ellaiah P, Prabhakhar T (2008) Urokinase-a very popular cardiovascular agent. Recent Pat Cardiovasc Drug Discovery 3(1):45–58

    CAS  Google Scholar 

  16. Ploug J, Kjeldgaard NO (1957) Urokinase an activator of plasminogen from human urine I. Isolation and properties. Biochim Biophys Acta 24:278–282

    CAS  PubMed  Google Scholar 

  17. van Hinsbergh VW (1988) Regulation of the synthesis and secretion of plasminogen activators by endothelial cells. Pathophysiol Haemost Thromb 18(4–6):307–327

    Google Scholar 

  18. Larsen G, Henson K, Blue Y (1988) Variants of human tissue-type plasminogen activator. Fibrin binding, fibrinolytic, and fibrinogenolytic characterization of genetic variants lacking the fibronectin finger-like and/or the epidermal growth factor domains. J Biol Chem 263(2):1023–1029

    CAS  PubMed  Google Scholar 

  19. Yakovlev S, Makogonenko E, Kurochkina N, Nieuwenhuizen W, Ingham K, Medved L (2000) Conversion of fibrinogen to fibrin: mechanism of exposure of tPA-and plasminogen-binding sites. Biochemistry 39(51):15730–15741

    CAS  PubMed  Google Scholar 

  20. Adams HP, Adams RJ, Brott T, Del Zoppo GJ, Furlan A, Goldstein LB et al (2003) Guidelines for the early management of patients with ischemic stroke: a scientific statement from the Stroke Council of the American Stroke Association. Stroke 34(4):1056–1083

    PubMed  Google Scholar 

  21. Adams HP, Del Zoppo G, Alberts MJ, Bhatt DL, Brass L, Furlan A et al (2007) Guidelines for the early management of adults with ischemic stroke. Circulation 115(20):e478–e534

    PubMed  Google Scholar 

  22. Baruah DB, Dash RN, Chaudhari M, Kadam S (2006) Plasminogen activators: a comparison. Vascul Pharmacol 44(1):1–9

    CAS  PubMed  Google Scholar 

  23. Shibata H, Nagaoka M, Sakai M, Sawada H, Watanabe T, Yokokura T (1994) Kinetic studies on the plasminogen activation by the staphylokinase-plasmin complex. J Biochem 115(4):738–742

    CAS  PubMed  Google Scholar 

  24. Nordt TK, Bode C (2003) Thrombolysis: newer thrombolytic agents and their role in clinical medicine. Heart 89(11):1358–1362

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Kunamneni A, Durvasula R (2014) Streptokinase-a drug for thrombolytic therapy: a patent review. Recent Pat Cardiovasc Drug Discov 9(2):106–121

    CAS  Google Scholar 

  26. Huai Q, Mazar AP, Kuo A, Parry GC, Shaw DE, Callahan J et al (2006) Structure of human urokinase plasminogen activator in complex with its receptor. Science 311(5761):656–659

    CAS  PubMed  Google Scholar 

  27. Khosla S, Jain P, Manda R, Razminia M, Guerrero M, Trivedi A et al (2003) Acute and long-term results after intra-arterial thrombolysis of occluded lower extremity bypass grafts using recombinant tissue plasminogen activator for acute limb-threatening ischemia. Am J Ther 10(1):3–6

    PubMed  Google Scholar 

  28. Mundada LV, Prorok M, DeFord ME, Figuera M, Castellino FJ, Fay WP (2003) Structure-function analysis of the streptokinase amino terminus (residues 1–59). J Biol Chem 278(27):24421–24427

    CAS  PubMed  Google Scholar 

  29. Anderson JL (1987) Development and evaluation of anisoylated plasminogen streptokinase activator complex (APSAC) as a second generation thrombolytic agent. J Am Coll Cardiol 10(5):22B–27B

    CAS  PubMed  Google Scholar 

  30. Nguyen THT, Quyen DT (2012) High-level expression, purification and properties of a fully active even glycosylated staphylokinase variant SakfC from Staphylococcus aureus QT08 in Pichia pastoris. Afr J Microbiol Res 6(9):2129–2136

    CAS  Google Scholar 

  31. Dalal J, Sahoo PK, Singh RK, Dhall A, Kapoor R, Krishnamurthy A et al (2013) Role of thrombolysis in reperfusion therapy for management of AMI: Indian scenario. Indian Heart J 65(5):566

    PubMed  PubMed Central  Google Scholar 

  32. White HD (1998) Thrombolytic therapy and equivalence trials. Q J Cardiol 3:269–271

    Google Scholar 

  33. Koster R, Cohen A, Hopkins G, Beier H, Günzler W, van der Wouw P (1994) Pharmacokinetics and pharmacodynamics of saruplase, an unglycosylated single-chain urokinase-type plasminogen activator, in patients with acute myocardial infarction. Thromb Haemost 72(5):740–744

    CAS  PubMed  Google Scholar 

  34. Cutler D, Bode C, Runge MS (1995) The promise of new genetically engineered plasminogen activators. J Vasc Interv Radiol 6(6):3S–7S

    CAS  PubMed  Google Scholar 

  35. Ross AM (1999) New plasminogen activators: a clinical review. Clin Cardiol 22(3):165–171

    CAS  PubMed  Google Scholar 

  36. Lee H-J, Im H-N (2010) Soluble expression and purification of human tissue-type plasminogen activator protease domain. Bull Korean Chem Soc 31(9):2607–2612

    CAS  Google Scholar 

  37. Rijken DC, Collen D (1981) Purification and characterization of the plasminogen activator secreted by human melanoma cells in culture. J Biol Chem 256(13):7035–7041

    CAS  PubMed  Google Scholar 

  38. Novokhatny VV, Ingham KC, Medved LV (1991) Domain structure and domain-domain interactions of recombinant tissue plasminogen activator. J Biol Chem 266(20):12994–13002

    CAS  PubMed  Google Scholar 

  39. Rijken D, Otter M, Kuiper J, Van Berkel TJ (1990) Receptor-mediated endocytosis of tissue-type plasminogen activator (t-PA) by liver cells. Thromb Res 57:63–71

    Google Scholar 

  40. Adivitiya Khasa YP (2017) The evolution of recombinant thrombolytics: Current status and future directions. Bioengineered 8(4):331–358

    PubMed  Google Scholar 

  41. Larsen GR, Metzger M, Henson K, Blue Y, Horgan P (1989) Pharmacokinetic and distribution analysis of variant forms of tissue-type plasminogen activator with prolonged clearance in rat. Blood 73(7):1842–1850

    CAS  PubMed  Google Scholar 

  42. Flemmig M, Melzig MF (2012) Serine-proteases as plasminogen activators in terms of fibrinolysis. J Pharm Pharmacol 64(8):1025–1039

    CAS  PubMed  Google Scholar 

  43. Liotta L, Goldfarb R, Brundage R, Siegal G, Terranova V, Garbisa S (1981) Effect of plasminogen activator (urokinase), plasmin, and thrombin on glycoprotein and collagenous components of basement membrane. Cancer Res 41(11):4629

    CAS  PubMed  Google Scholar 

  44. Topol EJ, Morris DC, Smalling RW, Schumacher RR, Taylor CR, Nishikawa A et al (1987) A multicenter, randomized, placebo-controlled trial of a new form of intravenous recombinant tissue-type plasminogen activator (activase) in acute myocardial infarction. J Am Coll Cardiol 9(6):1205–1213

    CAS  PubMed  Google Scholar 

  45. Mudduluru G, Medved F, Grobholz R, Jost C, Gruber A, Leupold JH et al (2007) Loss of programmed cell death 4 expression marks adenoma-carcinoma transition, correlates inversely with phosphorylated protein kinase B, and is an independent prognostic factor in resected colorectal cancer. Cancer 110(8):1697–1707. https://doi.org/10.1002/cncr.22983

    Article  CAS  PubMed  Google Scholar 

  46. Widimsky P, Coram R, Abou-Chebl A (2013) Reperfusion therapy of acute ischaemic stroke and acute myocardial infarction: similarities and differences. Eur Heart J 35(3):147–155

    PubMed  PubMed Central  Google Scholar 

  47. Wilcox R, Von der Lippe G, Olsson C, Jensen G, Skene A, Hampton J (1990) Effects of alteplase in acute myocardial infarction: 6-month results from the ASSET study. Lancet 335(8699):1175–1178

    CAS  PubMed  Google Scholar 

  48. Wardlaw JM, Murray V, Berge E, Del Zoppo G, Sandercock P, Lindley RL et al (2012) Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis. Lancet 379(9834):2364–2372

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Berge E, Cohen G, Roaldsen MB, Lundström E, Isaksson E, Rudberg A-S et al (2016) Effects of alteplase on survival after ischaemic stroke (IST-3): 3 year follow-up of a randomised, controlled, open-label trial. Lancet Neurol 15(10):1028–1034

    CAS  PubMed  Google Scholar 

  50. Anderson CS, Robinson T, Lindley RI, Arima H, Lavados PM, Lee T-H et al (2016) Low-dose versus standard-dose intravenous alteplase in acute ischemic stroke. N Engl J Med 374(24):2313–2323

    CAS  PubMed  Google Scholar 

  51. Mimuro J, Kaneko M, Murakami T, Matsuda M, Sakata Y (1992) Reversible interactions between plasminogen activators and plasminogen activator inhibitor-1. Biochim Biophysi Acta 1160(3):325–334

    CAS  Google Scholar 

  52. Biswas S, Sasaki J, Braunfeld M (2015) Anticoagulant drugs. Essentials of pharmacology anesthesia, pain medicine critical care. Springer, New York, pp 397–413

    Google Scholar 

  53. Swedberg K (1992) ISSIS-3 (Third International Study of Infarct Survival) Collaborative Gruop. ISIS-3 a randomized trial of streptokinase versus Tissue plasmino gen activator versus anistreplase and aspirin plus heparine vs aspirina lone among 41229 cases of suspected acute myocardial infarction. Lancet 339:753–770

    Google Scholar 

  54. Craig CS, Stitzel RE (1994) Modern pharmacology, 4th edn. Little, Brown and Company, New York, p 320

    Google Scholar 

  55. Verstraete M (2000) Third-generation thrombolytic drugs. Am J Med 109(1):52–58

    CAS  PubMed  Google Scholar 

  56. Tanswell P, Modi N, Combs D, Danays T (2002) Pharmacokinetics and pharmacodynamics of tenecteplase in fibrinolytic therapy of acute myocardial infarction. Clin Pharmacokinet 41(15):1229–1245

    CAS  PubMed  Google Scholar 

  57. Lapchak PA, Araujo DM, Zivin JA (2004) Comparison of Tenecteplase with Alteplase on clinical rating scores following small clot embolic strokes in rabbits. Exp Neurol 185(1):154–159

    CAS  PubMed  Google Scholar 

  58. Melandri G, Vagnarelli F, Calabrese D, Semprini F, Nanni S, Branzi A (2009) Review of tenecteplase (TNKase) in the treatment of acute myocardial infarction. Vasc Health Risk Manag 5:249

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Van de Werf F (1999) Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial. Lancet 354(9180):716–722

    Google Scholar 

  60. Collen D, Lijnen H (2000) Recent developments in thrombolytic therapy. Fibrinol Proteol 14(2–3):66–72

    CAS  Google Scholar 

  61. Inoue T, Nishiki R, Kageyama M, Node K (2004) Therapeutic potential of monteplase in acute myocardial infarction as a powerful thrombolytic agent for pretreatment of coronary intervention. Cardiovasc Drug Rev 22(4):320–333

    CAS  PubMed  Google Scholar 

  62. Bode C, Smalling R, Sen S, Kalbfleisch J, Boehm E, Odenheimer D et al., (ed) (1993) Recombinant plasminogen-activator angiographic phase-ii international dose-finding study (rapid)-patency analysis and mortality end-points. Circulation AMER HEART ASSOC 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596

  63. Baldo BA (2015) Enzymes approved for human therapy: indications, mechanisms and adverse effects. BioDrugs. 29(1):31–55

    CAS  PubMed  Google Scholar 

  64. Ohman EM, Harrington RA, Cannon CP, Agnelli G, Cairns JA, Kennedy JW (2001) Intravenous thrombolysis in acute myocardial infarction. Chest 119(1):253S–277S

    CAS  PubMed  Google Scholar 

  65. Ellis K, Brener S (2004) New fibrinolytic agents for MI: as effective as current agents, but easier to administer. Clevel Clin J Med 71(1):20–39

    Google Scholar 

  66. Wander GS, Chhabra ST (2013) Critical analysis of various drugs used for thrombolytic therapy in acute myocardial infarction. Med Updat 23:109–116

    Google Scholar 

  67. Ueshima S, Matsuo O (2006) Development of new fibrinolytic agents. Curr Pharm Des 12(7):849–857

    CAS  PubMed  Google Scholar 

  68. Bosques-Padilla FJ, Vázquez-Elizondo G, González-Santiago O, Del Follo-Martínez L, González OP, González-González JA et al (2015) Hypertriglyceridemia-induced pancreatitis and risk of persistent systemic inflammatory response syndrome. Am J Med Sci 349(3):206–211

    PubMed  Google Scholar 

  69. Oikawa K, Kamimura H, Watanabe T, Miyamoto I, Higuchi S (2001) Pharmacokinetic properties of a novel tissue-type plasminogen activator pamiteplase after single intravenous administration to rats, dogs, and monkeys. Thromb Res 101(6):493–500

    CAS  PubMed  Google Scholar 

  70. Bachmann F (2012) Fibrinolytics and antifibrinolytics. Springer Science & Business Media, New York

    Google Scholar 

  71. Collen D, Lijnen RH (2005) Thrombolytic agents. Thromb Haemost 93(04):627–630

    CAS  PubMed  Google Scholar 

  72. Ishikawa A, Ohata T, Imamura K, Iwasaki M, Sakai T, Matsuzawa T et al (1997) Single and repeated intravenous toxicity studies of pamiteplase (genetical recombination) in rats and monkeys. J Toxicol Sci 22(2):117–133

    CAS  PubMed  Google Scholar 

  73. Ieko M, Sawada K, Yasukouchi T, Sakurama S, Tohma Y, Shiroshita K et al (1997) Protection by α2-macroglobulin of tissue plasminogen activator against inhibition by plasminogen activator inhibitor-1. Br J Haematol 97(1):214–218

    CAS  PubMed  Google Scholar 

  74. Mican J, Toul M, Bednar D, Damborsky J (2019) Structural biology and protein engineering of thrombolytics. Comput Struct Biotechnol J 2(17):917–938

    Google Scholar 

  75. Malcolm A, Keltai M, Walsh M (1996) ESPRIT: a European study of the prevention of reocclusion after initial thrombolysis with duteplase in acute myocardial infarction. Eur Heart J 17(10):1522–1531

    CAS  PubMed  Google Scholar 

  76. Rijken DC, Barrett-Bergshoeff MM, Jie A, Criscuoli M, Sakharov DV (2004) Clot penetration and fibrin binding of amediplase, a chimeric plasminogen activator (K2tu-PA). Thromb Haemost 91(01):52–60

    CAS  PubMed  Google Scholar 

  77. Guimarães AH, Barrett-Bergshoeff MM, Criscuoli M, Evangelista S, Rijken DC (2006) Fibrinolytic efficacy of Amediplase, Tenecteplase and scu-PA in different external plasma clot lysis models. Thromb Haemost 96(09):325–330

    PubMed  Google Scholar 

  78. Gulba D, Bode C, Runge M, Huber K (1996) Thrombolytic agents–an overview. Ann Hematol 73:S9–S27

    CAS  PubMed  Google Scholar 

  79. Bode C, Peter K, Nordt T, Kohler B, Moser M, Ruef J et al (1997) New developments in thrombolytic therapy. Fibrinol Proteol 11:109–114. https://doi.org/10.1016/S0268-9499(97)80033-1

    Article  CAS  Google Scholar 

  80. Montoney M, Gardell SJ, Marder VJ (1995) Comparison of the bleeding potential of vampire bat salivary plasminogen activator versus tissue plasminogen activator in an experimental rabbit model. Circulation 91(5):1540–1544

    CAS  PubMed  Google Scholar 

  81. Zhang Y, Wisner A, Xiong Y, Bon C (1995) A novel plasminogen activator from snake venom purification, characterization, and molecular cloning. J Biol Chem 270(17):10246–10255

    CAS  PubMed  Google Scholar 

  82. Park D, Kim H, Chung K, Kim DS, Yun Y (1998) Expression and characterization of a novel plasminogen activator from Agkistrodon halys venom. Toxicon 36(12):1807–1819

    CAS  PubMed  Google Scholar 

  83. Sanchez EF, Felicori LF, Chavez-Olortegui C, Magalhaes HB, Hermogenes AL, Diniz MV et al (2006) Biochemical characterization and molecular cloning of a plasminogen activator proteinase (LV-PA) from bushmaster snake venom. Biochim Biophys Acta (BBA) 1760(12):1762–1771

    CAS  Google Scholar 

  84. Jiao J, Yu M, Ru B (2001) Characterization of a recombinant chimeric plasminogen activator with enhanced fibrin binding. Biochim Biophys Acta (BBA) 1546(2):399–405

    CAS  Google Scholar 

  85. Davami F, Sardari S, Majidzadeh AK, Hemayatkar M, Barkhrdari F, Omidi M et al (2010) Expression of a novel chimeric truncated t-PA in CHO cells based on in silico experiments. BioMed Res Int 2010:108159

    Google Scholar 

  86. Zhang L, Wang J, Yu M, Ru B (2004) Functional properties of a recombinant chimeric plasminogen activator with platelet-targeted fibrinolytic and anticoagulant potential. Mol Genet Metab 82(4):304–311

    CAS  PubMed  Google Scholar 

  87. Davidson FM (1960) The activation of plasminogen by staphylokinase: comparison with streptokinase. Biochem J 76(1):56

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Glanville KL (1963) A simple method of purifying staphylokinase. Biochem J 88(1):11

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Sweet B, McNicol G, Douglas A (1965) In vitro studies of staphylokinase. Clin Sci 29(2):375

    CAS  PubMed  Google Scholar 

  90. Lewis JH, Kerber C, Wilson JH (1964) Effects of fibrinolytic agents and heparin on intravascular clot lysis. Am J Physiol 207(5):1044–1048

    CAS  PubMed  Google Scholar 

  91. Lewis JH, Shirakawa M (1964) Effects of fibrinolytic agents and heparin on blood coagulation in dogs. Am J Physiol 207(5):1049–1052

    CAS  PubMed  Google Scholar 

  92. Kanae K (ed) (1986) Fibrinolysis by staphylokinase in vivo. Biol Abstr

  93. Jackson KW, Esmon N, Tang J (1981) Streptokinase and staphylokinase. Methods in enzymology. Elsevier, Amsterdam, pp 387–394

    Google Scholar 

  94. Kondo I, Itoh S, Takagi T (1981) Purification of staphylokinase by affinity chromatography with human plasminogen. Staphylococci Staphylococcal Infect

  95. Gerheim EB (1948) Staphlococcal coagulation and fibrinolysis. Nature 162(4123):732

    CAS  PubMed  Google Scholar 

  96. Lack CH (1948) Staphylokinase; an activator of plasma protease. Nature 161(4093):559

    CAS  PubMed  Google Scholar 

  97. Collen D, Lijnen H (1994) Staphylokinase, a fibrin-specific plasminogen activator with therapeutic potential? Blood 84(3):680–686

    CAS  PubMed  Google Scholar 

  98. Collen D, Schlott B, Engelborghs Y, Van Hoef B, Hartmann M, Lijnen H et al (1993) On the mechanism of the activation of human plasminogen by recombinant staphylokinase. J Biol Chem 268(11):8284–8289

    CAS  PubMed  Google Scholar 

  99. Sakai M, Watanuki M, Matsuo O (1989) Mechanism of fibrin-specific fibrinolysis by staphylokinase: participation of α2-plasmin inhibitor. Biochem Biophys Res Commun 162(2):830–837

    CAS  PubMed  Google Scholar 

  100. Lijnen HR, Van Hoef B, Matsuo O, Collen D (1992) On the molecular interactions between plasminogen-staphylokinase, α2-antiplasmin-formula > and fibrin. Biochim Biophys Acta (BBA) 1118(2):144–148

    CAS  Google Scholar 

  101. Okada K, Yuasa H, Hagiya Y, Fukao H, Ueshima S, Matsuo O (1994) Kinetic analysis of plasminogen activation by staphylokinase/plasminogen complex in the presence of fibrin. Thromb Res 76(2):181–191

    CAS  PubMed  Google Scholar 

  102. Lijnen H, Van Hoef B, De Cock F, Okada K, Ueshima S, Matsuo O et al (1991) On the mechanism of fibrin-specific plasminogen activation by staphylokinase. J Biol Chem 266(18):11826–11832

    CAS  PubMed  Google Scholar 

  103. Okada K, Ueshima S, Takaishi T, Yuasa H, Fukao H, Matsuo O (1996) Effects of fibrin and α2-antiplasmin on plasminogen activation by staphylokinase. Am J Hematol 53(3):151–157

    CAS  PubMed  Google Scholar 

  104. http://www.thrombogenics.com

  105. Bokarewa MI, Jin T, Tarkowski A (2006) Staphylococcus aureus: staphylokinase. Int J Biochem Cell Biol 38(4):504–509

    CAS  PubMed  Google Scholar 

  106. Jackson KW, Tang J (1982) Complete amino acid sequence of streptokinase and its homology with serine proteases. Biochemistry 21(26):6620–6625

    CAS  PubMed  Google Scholar 

  107. Damaschun G, Damaschun H, Gast K, Misselwitz R, Zirwer D, Gührs K-H et al (1993) Physical and conformational properties of staphylokinase in solution. Biochim Biophys Acta (BBA) 1161(2–3):244–248

    CAS  Google Scholar 

  108. Kwieciński J, Josefsson E, Mitchell J, Higgins J, Magnusson M, Foster T et al (2010) Activation of plasminogen by staphylokinase reduces the severity of Staphylococcus aureus systemic infection. J Infect Dis 202(7):1041–1049

    PubMed  Google Scholar 

  109. Kim J-H, Wong S-L, Kim B-G (2001) Optimization of staphylokinase production inBacillus subtilis using inducible and constitutive promoters. Biotechnol Bioprocess Eng 6(3):167

    CAS  Google Scholar 

  110. Schlott B, Hartmann M, Gührs K-H, Birch-Hirschfeld E, Gase A, Vettermann S et al (1994) Functional properties of recombinant staphylokinase variants obtained by site-specific mutagenesis of methionine-26. Biochim Biophys Acta (BBA) 1204(2):235–242

    CAS  Google Scholar 

  111. Laroche Y, Heymans S, Capaert S, De Cock F, Demarsin E, Collen D (2000) Recombinant staphylokinase variants with reduced antigenicity due to elimination of B-lymphocyte epitopes. Blood 96(4):1425–1432

    CAS  PubMed  Google Scholar 

  112. Szemraj J, Walkowiak B, Kawecka I, Janiszewska G, Janiszewska G, Buczko W, Bartkowiak J et al (2005) IN FOCUS: a new recombinant thrombolytic and antithrombotic agent with higher fibrin affinity–a staphylokinase variant. I. In vitro study. J Thromb Haemost 3(10):2156–2165

    CAS  PubMed  Google Scholar 

  113. Moreadith RW, Collen D (2003) Clinical development of PEGylated recombinant staphylokinase (PEG–Sak) for bolus thrombolytic treatment of patients with acute myocardial infarction. Adv Drug Deliv Rev 55(10):1337–1345

    CAS  PubMed  Google Scholar 

  114. Moons L, Vanlinthout I, Roelants I, Moreadith R, Collen D, Rapold HJ (2001) toxicology studies with recombinant staphylokinase and with SY 161-P5, a polyethylene glycol-derivatized Cysteine-Substitution Mutant. Toxicol Pathol 29(3):285–291

    CAS  PubMed  Google Scholar 

  115. Liu J, Wang Z, He J, Wang G, Zhang R, Zhao B (2014) Effect of site-specific PEGylation on the fibrinolytic activity, immunogenicity, and pharmacokinetics of staphylokinase. Acta Biochim Biophys Sin 46(9):782–791

    CAS  PubMed  Google Scholar 

  116. Mannully ST, Shanthi C, Pulicherla KK (2019) Lipid modification of staphylokinase and its implications on stability and activity. Int J Biol Macromol 121:1037–1045

    CAS  PubMed  Google Scholar 

  117. Yasuda T, Gold HK, Yaoita H, Leinbach RC, Guerrero JL, Jang I-K et al (1990) Comparative effects of aspirin, a synthetic thrombin inhibitor and a monoclonal antiplatelet glycoprotein IIb/IIIa antibody on coronary artery reperfusion, reocclusion and bleeding with recombinant tissue-type plasminogen activator in a canine preparation. J Am Coll Cardiol 16(3):714–722

    CAS  PubMed  Google Scholar 

  118. Savage B, Marzec U, Chao B, Harker L, Maraganore J, Ruggeri ZM (1990) Binding of the snake venom-derived proteins applaggin and echistatin to the arginine-glycine-aspartic acid recognition site (s) on platelet glycoprotein IIb. IIIa complex inhibits receptor function. J Biol Chem 265(20):11766–11772

    CAS  PubMed  Google Scholar 

  119. Coller BS, Folts JD, Smith SR, LE Scudder, Jordan R (1989) Abolition of in vivo platelet thrombus formation in primates with monoclonal antibodies to the platelet GPIIb/IIIa receptor. Correlation with bleeding time, platelet aggregation, and blockade of GPIIb/IIIa receptors. Circulation 80(6):1766–1774

    CAS  PubMed  Google Scholar 

  120. Rydel TJ, Ravichandran K, Tulinsky A, Bode W, Huber R, Roitsch C et al (1990) The structure of a complex of recombinant hirudin and human alpha-thrombin. Science 249(4966):277–280

    CAS  PubMed  Google Scholar 

  121. Cappello M, Li S, Chen X, Li C-B, Harrison L, Narashimhan S et al (1998) Tsetse thrombin inhibitor: bloodmeal-induced expression of an anticoagulant in salivary glands and gut tissue of Glossina morsitans morsitans. Proc Natl Acad Sci 95(24):14290–14295

    CAS  PubMed  Google Scholar 

  122. Wang M, Wang Y, Wang J, Zou M, Liu S, Xu T et al (2009) Construction and characterization of a novel staphylokinase variant with thrombin-inhibitory activity. Biotechnol Lett 31(12):1923–1927

    CAS  PubMed  Google Scholar 

  123. Skrzypczak-Jankun E, Carperos VE, Ravichandran K, Tulinsky A, Westbrook M, Maraganore JM (1991) Structure of the hirugen and hirulog 1 complexes of α-thrombin. J Mol Biol 221(4):1379–1393

    CAS  PubMed  Google Scholar 

  124. Van Zyl WB, Pretorius GH, Hartmann M, Kotzé HF (1997) Production of a recombinant antithrombotic and fibrinolytic protein, PLATSAK in Escherichia coli. Thromb Res 88(5):419–426

    PubMed  Google Scholar 

  125. Icke C, Schlott B, Ohlenschläger O, Hartmann M, Gührs K-H, Glusa E (2002) Fusion proteins with anticoagulant and fibrinolytic properties: functional studies and structural considerations. Mol Pharmacol 62(2):203–209

    CAS  PubMed  Google Scholar 

  126. Seetha Ram K, Peravali JB, Sudheer Y, Anmol K, Rao KRSSS, Pulicherla KK (2013) Large scale production of soluble recombinant staphylokinase variant from cold shock expression system using IPTG inducible E. coli BL21(DE3). Int J Bio-Sci Bio-Technol 5(4):107–116

    Google Scholar 

  127. Cappello M, Li S, Chen X, Li CB, Harrison L, Narashimhan S et al (1998) Tsetse thrombin inhibitor: bloodmeal-induced expression of an anticoagulant in salivary glands and gut tissue of Glossina morsitans morsitans. Proc Natl Acad Sci USA 95(24):14290–14295. https://doi.org/10.1073/pnas.95.24.14290

    Article  CAS  PubMed  Google Scholar 

  128. Neeper M, Waxman L, Smith D, Schulman C, Sardana M, Ellis R et al (1990) Characterization of recombinant tick anticoagulant peptide. A highly selective inhibitor of blood coagulation factor Xa. J Biol Chem 265(29):17746–17752

    CAS  PubMed  Google Scholar 

  129. Gruber A, Hanson SR, Kelly AB, Yan BS, Bang N, Griffin JH et al (1990) Inhibition of thrombus formation by activated recombinant protein C in a primate model of arterial thrombosis. Circulation 82(2):578–585

    CAS  PubMed  Google Scholar 

  130. Kotra SR, Peravali J, Yanamadala S, Kumar A, Samba Siva Rao K, Pulicherla K (2013) Large scale production of soluble recombinant staphylokinase variant from cold shock expression system using IPTG inducible E. coli BL21 (DE3). Int J Bio-Sci Bio-Technol 5:107–116

    Google Scholar 

  131. Nguyen THT, Quyen DT (2012) Cloning, high-level expression, purification and characterization of a staphylokinase variant, SakøC, from Staphylococcus aureus QT08 in Escherichia coli BL21. Afr J Biotech 11(22):5995–6003

    CAS  Google Scholar 

  132. Reddy YGP, Prakash R, Anandakumar S (2014) Isolation, cloning and expression of recombinant staphylokinase gene against thrombosis. J Pharm Pharm Sci. 6(4):266–270

    Google Scholar 

  133. Jasim H, Dellol R, Hamzah A (2015) Optimum conditions of staphylokinase production cloned in E. coli Jm109 (DE3). Int J Curr Microbiol Appl Sci 4(12):10–19

    CAS  Google Scholar 

  134. Gerlach D, Kraft R, Behnke D (1988) Purification and characterization of the bacterial plasminogen activator staphylokinase secreted by a recombinant Bacillus subtilis. Zentralblatt für Bakteriologie, Mikrobiologie und Hygiene Series A 269(3):314–322

    CAS  Google Scholar 

  135. Ye R, Kim JH, Kim BG, Szarka S, Sihota E, Wong SL (1999) High-level secretory production of intact, biologically active staphylokinase from Bacillus subtilis. Biotechnol Bioeng 62(1):87–96

    CAS  PubMed  Google Scholar 

  136. Pulicherla K, Seetharam K, Kumar A, Rekha V, Rao K (2012) Cloning and high level expression of recombinant heterologous fusion protein SAK RGD in methanol inducible Pichia pastoris GS115. Int J Res Pharm Biomed Sci 3:1008–1013

    CAS  Google Scholar 

  137. Apte-Deshpnade A, Mandal G, Soorapaneni S, Prasad B, Kumar J, Padmanabhan S (2009) High-level expression of non-glycosylated and active staphylokinase from Pichia pastoris. Biotechnol Lett 31(6):811–817

    CAS  PubMed  Google Scholar 

  138. Cheng Y, Li Y, Liu B, Guo L (1998) Cloning and secretory expression of staphylokinase in Streptomyces lividans. Zhongguo yi xue ke xue yuan xue bao Acta Academiae Medicinae Sinicae. 20(6):428–432

    CAS  PubMed  Google Scholar 

  139. Moussa M, Ibrahim M, El Ghazaly M, Rohde J, Gnoth S, Anton A et al (2012) Expression of recombinant staphylokinase in the methylotrophic yeast Hansenula polymorpha. BMC Biotechnol 12(1):96

    CAS  PubMed  PubMed Central  Google Scholar 

  140. Grinna LS, Tschopp JF (1989) Size distribution and general structural features of N-linked oligosaccharides from the methylotrophic yeast. Pichia pastoris. Yeast. 5(2):107–115

    CAS  PubMed  Google Scholar 

  141. Kim H, Thak EJ, Lee D-J, Agaphonov MO, Kang HA (2015) Hansenula polymorpha Pmt4p plays critical roles in O-mannosylation of surface membrane proteins and participates in heteromeric complex formation. PLoS ONE 10(7):e0129914

    PubMed  PubMed Central  Google Scholar 

  142. Cregg JM, Vedvick TS, Raschke WC (1993) Recent advances in the expression of foreign genes in Pichia pastoris. Bio/Technology 11(8):905

    CAS  PubMed  Google Scholar 

  143. Miele RG, Prorok M, Costa VA, Castellino FJ (1999) Glycosylation of asparagine-28 of recombinant staphylokinase with high-mannose-type oligosaccharides results in a protein with highly attenuated plasminogen activator activity. J Biol Chem 274(12):7769–7776

    CAS  PubMed  Google Scholar 

  144. Schlott B, Guhrs KH, Hartmann M, Rocker A, Collen D (1997) Staphylokinase requires NH2-terminal proteolysis for plasminogen activation. J Biol Chem 272(9):6067–6072. https://doi.org/10.1074/jbc.272.9.6067

    Article  CAS  PubMed  Google Scholar 

  145. Mandi N, Soorapaneni S, Rewanwar S, Kotwal P, Prasad B, Mandal G et al (2009) High yielding recombinant Staphylokinase in bacterial expression system–cloning, expression, purification and activity studies. Protein Expr Purif 64(1):69–75. https://doi.org/10.1016/j.pep.2008.10.010

    Article  CAS  PubMed  Google Scholar 

  146. Schlott B, Hartmann M, Gührs K-H, Birch-Hirschfeid E, Pohl H-D, Vanderschueren S et al (1994) High yield production and purification of recombinant staphylokinase for thrombolytic therapy. Bio/Technology 12(2):185–189. https://doi.org/10.1038/nbt0294-185

    Article  CAS  PubMed  Google Scholar 

  147. Lee SJ, Kim IC, Kim DM, Bae KH, Byun SM (1998) High level secretion of recombinant staphylokinase into periplasm of Escherichia coli. Biotechnol Lett 20(2):113–116. https://doi.org/10.1023/a:1005359920522

    Article  CAS  Google Scholar 

  148. Liu W, Zhu R-H, Li G-P, Wang D-C (2002) cDNA cloning, high-level expression, purification, and characterization of an avian Cu, Zn superoxide dismutase from Peking duck. Protein Expr Purif 25(3):379–388. https://doi.org/10.1016/S1046-5928(02)00040-2

    Article  CAS  PubMed  Google Scholar 

  149. Schlott B, Hartmann M, Gührs K-H, Birch-Hirschfeid E, Pohl H-D, Vanderschueren S et al (1994) High yield production and purification of recombinant staphylokinase for thrombolytic therapy. Nat Biotechnol 12(2):185

    CAS  Google Scholar 

  150. Schlott B, Gührs K-H, Hartmann M, Röcker A, Collen D (1997) Staphylokinase requires NH2-terminal proteolysis for plasminogen activation. J Biol Chem 272(9):6067–6072

    CAS  PubMed  Google Scholar 

  151. Mandi N, Soorapaneni S, Rewanwar S, Kotwal P, Prasad B, Mandal G et al (2009) High yielding recombinant Staphylokinase in bacterial expression system—cloning, expression, purification and activity studies. Protein Expr Purif 64(1):69–75

    CAS  PubMed  Google Scholar 

  152. Pulicherla K, Gadupudi G, Rekha V, Seetharam K, Kumar A, Rao K (2011) Isolation, cloning and expression of mature staphylokinase from lysogenic Staphylococcus aureus collected from a local wound sample in a salt inducible E. coli expression host. Int J Adv Sci Technol 30:35–42

    Google Scholar 

  153. Faraji H, Ramezani M, Sadeghnia HR, Abnous K, Soltani F, Mashkani B (2017) High-level expression of a biologically active staphylokinase in Pichia pastoris. Prep Biochem Biotechnol 47(4):379–387

    CAS  PubMed  Google Scholar 

  154. Kotra SR, Kumar A, Rao KS, Pulicherla K (2012) Statistical optimization of media components for enhanced production of the recombinant staphylokinase variant from salt inducible E. Coli GJ1158. Int J Bio-Sci Bio-Technol 4(4):27–40

    Google Scholar 

  155. Lian Q, Szarka SJ, Ng KK, Wong S-L (2003) Engineering of a staphylokinase-based fibrinolytic agent with antithrombotic activity and targeting capability toward thrombin-rich fibrin and plasma clots. J Biol Chem 278(29):26677–26686

    CAS  PubMed  Google Scholar 

  156. Chen H, Mo W, Zhang Y, Su H, Ma J, Yao R et al (2007) Functional properties of a novel mutant of staphylokinase with platelet-targeted fibrinolysis and antiplatelet aggregation activities. Eur J Pharmacol 566(1–3):137–144

    CAS  PubMed  Google Scholar 

  157. Szarka S, Sihota E, Habibi H, Wong S-L (1999) Staphylokinase as a plasminogen activator component in recombinant fusion proteins. Appl Environ Microbiol 65(2):506–513

    CAS  PubMed  PubMed Central  Google Scholar 

  158. Szemraj J, Zakrzeska A, Brown G, Stankiewicz A, Gromotowicz A, Grędziński T et al (2011) New derivative of staphylokinase SAK-RGD-K2-Hirul exerts thrombolytic effects in the arterial thrombosis model in rats. Pharmacol Rep 63(5):1169–1179

    CAS  PubMed  Google Scholar 

  159. Mo W, Zhang Y-L, Chen H-S, Wang L-S, Song H-Y (2009) A novel hirudin derivative characterized with anti-platelet aggregations and thrombin inhibition. J Thromb Thromb 28(2):230–237

    CAS  Google Scholar 

  160. Kumar A, Kumar A, Pulicherla KK, Mayuren C, Kotra S, Rao KRS (2013) Evaluation of a multifunctional staphylokinase variant with thrombin inhibition and antiplatelet aggregation activities produced from salt-inducible E. coli GJ1158. Can J Physiol Pharmacol 91(10):839–847

    CAS  PubMed  Google Scholar 

  161. Vanderschueren S, Collen D, Van de Werf F (1996) Current clinical experience with staphylokinase in arterial thrombosis. J Thromb Thromb 3(4):297–300

    CAS  Google Scholar 

  162. Armstrong P, Burton J, Pakola S, Molhoek P, Betriu A, Tendera M et al (2003) Collaborative angiographic patency trial of recombinant staphylokinase (CAPTORS II). Am Heart J 146(3):484–488

    CAS  PubMed  Google Scholar 

  163. Armstrong PW, Burton JR, Palisaitis D, Thompson CR, Ban de Werf F et al (2000) Collaborative angiographic patency trial of recombinant staphylokinase (CAPTORS). Am Heart J 139(5):820–823

    CAS  PubMed  Google Scholar 

  164. Collen D, Van de Werf F (1993) Coronary thrombolysis with recombinant staphylokinase in patients with evolving myocardial infarction. Circulation 87(6):1850–1853

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by Molecular Medicine Research Center, Hormozgan Health Institute and the Isfahan Cardiovascular Research Center. We appreciated Dr.Mostafa Khedri for her valuable comments.

Author information

Authors and Affiliations

  1. Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran

    Reza Nedaeinia

  2. Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

    Habibollah Faraji

  3. Department of Laboratory Sciences, Faculty of Para-Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

    Habibollah Faraji

  4. Applied Physiology Research Center, Cardiovascular Research Institute, Isfahan University of Medical Science, Isfahan, Iran

    Shaghayegh Haghjooye Javanmard

  5. Brighton and Sussex Medical School, Division of Medical Education, Falmer, Brighton, Sussex, BN1 9PH, UK

    Gordon A. Ferns

  6. Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Majid Ghayour-Mobarhan

  7. Department of Food Science and Technology, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan, Iran

    Mohammad Goli

  8. Department of Medical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Baratali Mashkani

  9. Young Researchers and Elite Club, Marvdasht Branch, Islamic Azad University, Marvdasht, Iran

    Mozhdeh Nedaeinia

  10. Department of Health Information Management, Faculty of Para-Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

    Mohammad Hossein Hayavi Haghighi

  11. Advanced Materials Research Center, Department of Materials Engineering, Najafabad Branch, Islamic Azad University, Najafabad, Iran

    Maryam Ranjbar

  12. Deputy of Food and Drug, Isfahan University of Medical Sciences, Isfahan, Iran

    Maryam Ranjbar

Authors
  1. Reza Nedaeinia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Habibollah Faraji
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shaghayegh Haghjooye Javanmard
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gordon A. Ferns
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Majid Ghayour-Mobarhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mohammad Goli
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Baratali Mashkani
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mozhdeh Nedaeinia
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Mohammad Hossein Hayavi Haghighi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Maryam Ranjbar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Habibollah Faraji.

Ethics declarations

Conflict of interest

The authors have declared no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nedaeinia, R., Faraji, H., Javanmard, S.H. et al. Bacterial staphylokinase as a promising third-generation drug in the treatment for vascular occlusion. Mol Biol Rep 47, 819–841 (2020). https://doi.org/10.1007/s11033-019-05167-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-019-05167-x

Keywords

Search

Navigation