1887

Abstract

The aim of the study was to determine whether Leonurus cardiaca L. herb extract (LCE) used at subinhibitory concentration modifies the characteristics of Staphylococcus aureus, which is important in the pathogenesis of invasive infections originating from the bloodstream, in a way favourable for the human host. Polyphenol-rich LCE, a common ingredient in pharmaceutical products used for various cardiovascular and nervous system disorders, had shown interesting antibacterial and antibiofilm properties in our previous studies. Our current findings indicate that the following S. aureus characteristics decreased, depending on the LCE concentration: (i) formation of aggregates in plasma, (ii) adherence to a fibrin-coated surface, (iii) staphylocoagulase-dependent plasma clotting, (iv) bacterial survival in whole human blood in an ex vivo model, (v) expression of cell surface protein A and (vi) synthesis of α-toxin. However, staphylococcal tolerance to exogenous hydrogen peroxide was enhanced after pre-incubation with LCE, possibly due to the increased activity of bacterial antioxidant enzymes, a possibility confirmed by the higher production of superoxide dismutase and slightly higher production of catalase. The use of LCE at sub-MIC in in vitro and ex vivo models resulted in the weakening of some important staphylococcal immunoprotective attributes but the strengthening of such virulence factors as those responsible for oxidative stress tolerance. Some of these results and the fact that LCE has direct anticoagulant properties, reflected in a reduced thrombin-dependent fibrinogen polymerization rate, suggest a risk of adverse effects, which could be important in the context of S. aureus survival in the host.

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2016-10-18
2019-12-05
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References

  1. Anderson M. J., Lin Y.-C., Gillman A. N., Parks P. J., Schlievert P. M., Peterson M. L..( 2012;). Alpha-toxin promotes Staphylococcus aureus mucosal biofilm formation. . Front Cell Infect Microbiol2:1–10. [CrossRef]
    [Google Scholar]
  2. Battistoni A..( 2003;). Role of prokaryotic Cu, Zn superoxide dismutase in pathogenesis. . Biochem Soc Trans31:1326–1329. [CrossRef][PubMed]
    [Google Scholar]
  3. Bijak M., Saluk J., Ponczek M. B., Nowak P..( 2013;). Antithrombin effect of polyphenol-rich extracts from black chokeberry and grape seeds. . Phytother Res27:71–76. [CrossRef][PubMed]
    [Google Scholar]
  4. Camargo M. S., Bonacorsi C., Kitagawa R. R., DA Fonseca L. M., Raddi M. S. G..( 2011;). Quercetin reduces Staphylococcus aureus interaction with neutrophils. . Int J Pharmacogn Phytochem Res3:85–88.
    [Google Scholar]
  5. Cheng A. G., McAdow M., Kim H. K., Bae T., Missiakas D. M., Schneewind O..( 2010;). Contribution of coagulases towards Staphylococcus aureus disease and protective immunity. . PLoS Pathog6:,e1001036. [CrossRef][PubMed]
    [Google Scholar]
  6. Clements M. O., Watson S. P., Foster S. J..( 1999;). Characterization of the major superoxide dismutase of Staphylococcus aureus and its role in starvation survival, stress resistance, and pathogenicity. . J Bacteriol181:3898–3903.[PubMed]
    [Google Scholar]
  7. Clinical Laboratory Standard Institute( 2009;). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically. 8th Approved Standard M07-A8. Wayne, PA:: Clinical and Laboratory Standards Institute;.
    [Google Scholar]
  8. Colavite P. M., Sartori A..( 2014;). Septic arthritis: immunopathogenesis, experimental models and therapy. . J Venom Anim Toxins Incl Trop Dis20:1–8. [CrossRef][PubMed]
    [Google Scholar]
  9. Committee on Herbal Medicinal Products (HMPC)( 2010;). Community herbal monograph on Leonurus cardiaca L., herba. . European Medicines Agency2010:127428.
    [Google Scholar]
  10. Cushnie T. P., Lamb A. J..( 2011;). Recent advances in understanding the antibacterial properties of flavonoids. . Int J Antimicrob Agents38: 99–107. [CrossRef][PubMed]
    [Google Scholar]
  11. Danesi F., Kroon P. A., Saha S., de Biase D., D'Antuono L. F., Bordoni A..( 2014;). Mixed pro- and anti-oxidative effects of pomegranate polyphenols in cultured cells. . Int J Mol Sci15:19458–19471. [CrossRef][PubMed]
    [Google Scholar]
  12. Dastgheyb S. S., Villaruz A. E., Le K. Y., Tan V. Y., Duong A. C., Chatterjee S. S., Cheung G. Y., Joo H. S., Hickok N. J., Otto M..( 2015;). Role of phenol-soluble modulins in formation of Staphylococcus aureus biofilms in synovial fluid. . Infect Immun83:2966–2975. [CrossRef][PubMed]
    [Google Scholar]
  13. Edwards A. M., Massey R. C..( 2011;). How does Staphylococcus aureus escape the bloodstream?. Trends Microbiol19:184–190. [CrossRef][PubMed]
    [Google Scholar]
  14. Fraga C. G., Galleano M., Verstraeten S. V., Oteiza P. I..( 2010;). Basic biochemical mechanisms behind the health benefits of polyphenols. . Mol Aspects Med31:435–445. [CrossRef][PubMed]
    [Google Scholar]
  15. Gaupp R., Ledala N., Somerville G. A..( 2012;). Staphylococcal response to oxidative stress. . Frontiers Cell Infect Microbiol2:1–19. [CrossRef]
    [Google Scholar]
  16. Ginsburg I., Kohen R., Shalish M., Varon D., Shai E., Koren E..( 2013;). The oxidant-scavenging abilities in the oral cavity may be regulated by a collaboration among antioxidants in saliva, microorganisms, blood cells and polyphenols: a chemiluminescence-based study. . PLoS One8:,e63062. [CrossRef][PubMed]
    [Google Scholar]
  17. Haaber J., Cohn M. T., Frees D., Andersen T. J., Ingmer H..( 2012;). Planktonic aggregates of Staphylococcus aureus protect against common antibiotics. . PLoS One7:,e41075. [CrossRef][PubMed]
    [Google Scholar]
  18. Hall J. W., Yang J., Guo H., Ji Y..( 2015;). The AirSR two-component system contributes to Staphylococcus aureus survival in human blood and transcriptionally regulates sspABC operon. . Front Microbiol6:1–12. [CrossRef]
    [Google Scholar]
  19. Halliwell B..( 2008;). Are polyphenols antioxidants or pro-oxidants? what do we learn from cell culture and in vivo studies?. Arch Biochem Biophys476:107–112. [CrossRef][PubMed]
    [Google Scholar]
  20. Heras B., Scanlon M. J., Martin J. L..( 2015;). Targeting virulence not viability in the search for future antibacterials. . Br J Clin Pharmacol79: 208–215. [CrossRef][PubMed]
    [Google Scholar]
  21. Johannessen M., Sollid J. E., Hanssen A. M..( 2012;). Host- and microbe determinants that may influence the success of S. aureus colonization. . Front Cell Infect Microbiol2:1–14. [CrossRef][PubMed]
    [Google Scholar]
  22. Jongerius I., von Köckritz-Blickwede M., Horsburgh M. J., Ruyken M., Nizet V., Rooijakkers S. H..( 2012;). Staphylococcus aureus virulence is enhanced by secreted factors that block innate immune defences. . J Innate Immun4:301–311. [CrossRef][PubMed]
    [Google Scholar]
  23. Kang S. S., Kim J. G., Lee T. H., Oh K. B..( 2006;). Flavonols inhibit sortases and sortase-mediated Staphylococcus aureus clumping to fibrinogen. . Biol Pharm Bull29:1751–1755. [CrossRef][PubMed]
    [Google Scholar]
  24. Khodaverdian V., Pesho M., Truitt B., Bollinger L., Patel P., Nithianantham S., Yu G., Delaney E., Jankowsky E., Shoham M..( 2013;). Discovery of antivirulence agents against methicillin-resistant Staphylococcus aureus. . Antimicrob Agents Chemother57:3645–3652. [CrossRef][PubMed]
    [Google Scholar]
  25. Kim H. K., Thammavongsa V., Schneewind O., Missiakas D..( 2012;). Recurrent infections and immune evasion strategies of Staphylococcus aureus. . Curr Opin Microbiol15:92–99. [CrossRef][PubMed]
    [Google Scholar]
  26. Loof T. G., Goldmann O., Naudin C., Mörgelin M., Neumann Y., Pils M. C., Foster S. J., Medina E., Herwald H..( 2015;). Staphylococcus aureus-induced clotting of plasma is an immune evasion mechanism for persistence within the fibrin network. . Microbiology161:621–627. [CrossRef][PubMed]
    [Google Scholar]
  27. McAdow M., Kim H. K., Dedent A. C., Hendrickx A. P., Schneewind O., Missiakas D. M..( 2011;). Preventing Staphylococcus aureus sepsis through the inhibition of its agglutination in blood. . PLoS Pathog7:,e1002307. [CrossRef][PubMed]
    [Google Scholar]
  28. McAdow M., Missiakas D. M., Schneewind O..( 2012;). Staphylococcus aureus secretes coagulase and von Willebrand factor binding protein to modify the coagulation cascade and establish host infections. . J Innate Immun4:141–148. [CrossRef][PubMed]
    [Google Scholar]
  29. Micota B., Sadowska B., Podsędek A., Redzynia M., Różalska B..( 2014;). Leonurus cardiaca L. herb – a derived extract and an ursolic acid as the factors affecting the adhesion capacity of Staphylococcus aureus in the context of infective endocarditis. . Acta Biochim Pol61:385–388.[PubMed]
    [Google Scholar]
  30. Oh K. B., Oh M. N., Kim J. G., Shin D. S., Shin J..( 2006;). Inhibition of sortase-mediated Staphylococcus aureus adhesion to fibronectin via fibronectin-binding protein by sortase inhibitors. . Appl Microbiol Biotechnol70:102–106. [CrossRef][PubMed]
    [Google Scholar]
  31. Painter K. L., Strange E., Parkhill J., Bamford K. B., Armstrong-James D., Edwards A. M..( 2015;). Staphylococcus aureus adapts to oxidative stress by producing H2O2-resistant small-colony variants via the SOS response. . Infect Immun83:1830–1844. [CrossRef][PubMed]
    [Google Scholar]
  32. Powers M. E., Wardenburg B. J..( 2014;). Igniting the fire: Staphylococcus aureus virulence factors in the pathogenesis of sepsis. . PLoS Pathog10:,e1003871. [CrossRef]
    [Google Scholar]
  33. Rozemeijer W., Fink P., Rojas E., Jones C. H., Pavliakova D., Giardina P., Murphy E., Liberator P., Jiang Q. et al.( 2014;). Evaluation of approaches to monitor Staphylococcus aureus virulence factor expression during human disease. . PLoS One10:,e0116945. [CrossRef]
    [Google Scholar]
  34. Salgado-Pabón W., Breshears L., Spaulding A. R., Merriman J. A., Stach C. S., Horswill A. R., Peterson M. L., Schlievert P. M..( 2013;). Superantigens are critical for Staphylococcus aureus infective endocarditis, sepsis, and acute kidney injury. . MBio4:,e0049413. [CrossRef][PubMed]
    [Google Scholar]
  35. Saw J. T., Bahari M. B., Ang H. H., Lim Y. H..( 2006;). Potential drug-herb interaction with antiplatelet/anticoagulant drugs. . Complement Ther Clin Pract12:236–241. [CrossRef][PubMed]
    [Google Scholar]
  36. Tahmouzi S., Ghodsi M..( 2014;). Optimum extraction of polysaccharides from motherwort leaf and its antioxidant and antimicrobial activities. . Carbohydr Polym112:396–403. [CrossRef][PubMed]
    [Google Scholar]
  37. Thammavongsa V., Kim H. K., Missiakas D., Schneewind O..( 2015;). Staphylococcal manipulation of host immune responses. . Nat Rev Microbiol13:529–543. [CrossRef][PubMed]
    [Google Scholar]
  38. Walker J. N., Crosby H. A., Spaulding A. R., Salgado-Pabón W., Malone C. L., Rosenthal C. B., Schlievert P. M., Boyd J. M., Horswill A. R..( 2013;). The Staphylococcus aureus ArlRS two-component system is a novel regulator of agglutination and pathogenesis. . PLoS Pathog9:,e1003819. [CrossRef][PubMed]
    [Google Scholar]
  39. Waller A. K., Sage T., Kumar C., Carr T., Gibbins J. M., Clarke S. R..( 2013;). Staphylococcus aureus lipoteichoic acid inhibits platelet activation and thrombus formation via the paf receptor. . J Infect Dis208:2046–2057. [CrossRef][PubMed]
    [Google Scholar]
  40. Wang L., Bi C., Cai H., Liu B., Zhong X., Deng X., Wang T., Xiang H., Niu X., Wang D..( 2015;). The therapeutic effect of chlorogenic acid against Staphylococcus aureus infection through sortase a inhibition. . Front Microbiol6:1031. [CrossRef][PubMed]
    [Google Scholar]
  41. Widmer E., Que Y. A., Entenza J. M., Moreillon P..( 2006;). New concepts in the pathophysiology of infective endocarditis. . Curr Infect Dis Rep8:271–279. [CrossRef][PubMed]
    [Google Scholar]
  42. Wojtyniak K., Szymański M., Matławska I..( 2013;). Leonurus cardiaca L. (motherwort): a review of its phytochemistry and pharmacology. . Phytother Res27:1115–1120. [CrossRef][PubMed]
    [Google Scholar]
  43. World Health Organization( 2010;). WHO monographs on medicinal plants commonly used in the newly independent states (NIS). . Herba Leonuri, 229–240.
    [Google Scholar]
  44. Zapotoczna M., McCarthy H., Rudkin J. K., O'Gara J. P., O'Neill E..( 2015;). An essential role for coagulase in Staphylococcus aureus biofilm development reveals new therapeutic possibilities for device-related infections. . J Infect Dis212:1883–1893. [CrossRef][PubMed]
    [Google Scholar]
  45. Zhang X., Liu Y., Gao Y., Dong J., Mu C., Lu Q., Shao N., Yang G..( 2011;). Inhibiting platelets aggregation could aggravate the acute infection caused by Staphylococcus aureus. . Platelets22:228–236. [CrossRef][PubMed]
    [Google Scholar]
  46. Zhang J., Liu H., Zhu K., Gong S., Dramsi S., Wang Y. T., Li J., Chen F., Zhang R. et al.( 2014;). Antiinfective therapy with a small molecule inhibitor of Staphylococcus aureus sortase. . Proc Natl Acad Sci U S A111:13517–13522. [CrossRef][PubMed]
    [Google Scholar]
  47. Zuo Z., Huang M., Kanfer I., Chow M. S. S., Cho W. C. S..( 2015;). Herb-drug interactions: systematic review, mechanisms, and therapies. . Evid Based Complement Alternat Med2015:239150. [CrossRef]
    [Google Scholar]
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