1887

Abstract

has developed many mechanisms to escape from human immune responses. To resist phagocytic clearance, expresses a polysaccharide capsule, which effectively masks the bacterial surface and surface-associated proteins, such as opsonins, from recognition by phagocytic cells. Additionally, secretion of the extracellular fibrinogen binding protein (Efb) potently blocks phagocytic uptake of the pathogen. Efb creates a fibrinogen shield surrounding the bacteria by simultaneously binding complement C3b and fibrinogen at the bacterial surface. By means of neutrophil phagocytosis assays with fluorescently labelled encapsulated serotype 5 (CP5) and serotype 8 (CP8) strains we compare the immune-modulating function of these shielding mechanisms. The data indicate that, in highly encapsulated strains, the polysaccharide capsule is able to prevent phagocytic uptake at plasma concentrations <10 %, but loses its protective ability at higher concentrations of plasma. Interestingly, Efb shows a strong inhibitory effect on both capsule-negative and encapsulated strains at all tested plasma concentrations. Furthermore, the results suggest that both shielding mechanisms can exist simultaneously and collaborate to provide optimal protection against phagocytosis at a broad range of plasma concentrations. As opsonizing antibodies will be shielded from recognition by either mechanism, incorporating both capsular polysaccharides and Efb in future vaccines could be of great importance.

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2016-07-01
2021-07-27
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References

  1. Albus A., Fournier J. M., Wolz C., Boutonnier A., Ranke M., Høiby N., Hochkeppel H., Döring G. 1998; Staphylococcus aureus capsular types and antibody response to lung infection in patients with cystic fibrosis. J Clin Microbiol 26:2505–2509
    [Google Scholar]
  2. Bestebroer J., Poppelier M. J., Ulfman L. H., Lenting P. J., Denis C. V., van Kessel K. P., van Strijp J. A., de Haas C. J. 2007; Staphylococcal superantigen-like 5 binds PSGL-1 and inhibits P-selectin-mediated neutrophil rolling. Blood 109:2936–2943 [View Article][PubMed]
    [Google Scholar]
  3. Boyle-Vavra S., Li X., Alam M. T., Read T. D., Sieth J., Cywes-Bentley C., Dobbins G., David M. Z., Kumar N. et al. 2015; USA300 and USA500 clonal lineages of Staphylococcus aureus do not produce a capsular polysaccharide due to conserved mutations in the cap5 locus. MBio 6:1–10 [View Article]
    [Google Scholar]
  4. Cheung G. Y., Wang R., Khan B. A., Sturdevant D. E., Otto M. 2011; Role of the accessory gene regulator agr in community-associated methicillin-resistant Staphylococcus aureus pathogenesis . Infect Immun 79:1927–1935 [View Article][PubMed]
    [Google Scholar]
  5. Cunnion K. M., Lee J. C., Frank M. M. 2001; Capsule production and growth phase influence binding of complement to Staphylococcus aureus . Infect Immun 69:6796–6803 [View Article][PubMed]
    [Google Scholar]
  6. Cunnion K. M., Zhang H. M., Frank M. M. 2003; Availability of complement bound to Staphylococcus aureus to interact with membrane complement receptors influences efficiency of phagocytosis. Infect Immun 71:656–662[PubMed] [CrossRef]
    [Google Scholar]
  7. Fattom A., Schneerson R., Watson D. C., Karakawa W. W., Fitzgerald D., Pastan I., Li X., Shiloach J., Bryla D. A. et al. 1993; Laboratory and clinical evaluation of conjugate vaccines composed of Staphylococcus aureus type 5 and type 8 capsular polysaccharides bound to Pseudomonas aeruginosa recombinant exoprotein A. Infect Immun 61:1023–1032[PubMed]
    [Google Scholar]
  8. Fattom A., Matalon A., Buerkert J., Taylor K., Damaso S., Boutriau D. 2015; Efficacy profile of a bivalent Staphylococcus aureus glycoconjugated vaccine in adults on hemodialysis: Phase III randomized study. Hum Vaccin Immunother 11:632–641 [View Article][PubMed]
    [Google Scholar]
  9. Foster T. J. 2005; Immune evasion by staphylococci. Nat Rev Microbiol 3:948–958 [View Article][PubMed]
    [Google Scholar]
  10. Foster T. J., Geoghegan J. A., Ganesh V. K., Höök M. 2013; Adhesion, invasion and evasion: the many functions of the surface proteins of Staphylococcus aureus . Nat Rev Microbiol 12:49–62 [CrossRef]
    [Google Scholar]
  11. Fowler V. G., Allen K. B., Moreira E. D., Moustafa M., Isgro F., Boucher H. W., Corey G. R., Carmeli Y., Betts R. et al. 2013; Effect of an investigational vaccine for preventing Staphylococcus aureus infections after cardiothoracic surgery: a randomized trial. JAMA 309:1368–1378 [View Article][PubMed]
    [Google Scholar]
  12. Gros P., Milder F. J., Janssen B. J. 2008; Complement driven by conformational changes. Nat Rev Immunol 8:48–58 [View Article][PubMed]
    [Google Scholar]
  13. Herbert S., Newell S. W., Lee C., Wieland K. P., Dassy B., Fournier J. M., Wolz C., Döring G. 2001; Regulation of Staphylococcus aureus type 5 and type 8 capsular polysaccharides by CO(2). J Bacteriol 183:4609–4613 [View Article][PubMed]
    [Google Scholar]
  14. Hochkeppel H. K., Braun D. G., Vischer W., Imm A., Sutter S., Staeubli U., Guggenheim R., Kaplan E. L., Boutonnier A. et al. 1987; Serotyping and electron microscopy studies of Staphylococcus aureus clinical isolates with monoclonal antibodies to capsular polysaccharide types 5 and 8. J Clin Microbiol 25:526–530[PubMed]
    [Google Scholar]
  15. Itoh S., Hamada E., Kamoshida G., Yokoyama R., Takii T., Onozaki K., Tsuji T. 2010; Staphylococcal superantigen-like protein 10 (SSL10) binds to human immunoglobulin G (IgG) and inhibits complement activation via the classical pathway. Mol Immunol 47:932–938 [View Article][PubMed]
    [Google Scholar]
  16. Jones C. 2005; Revised structures for the capsular polysaccharides from Staphylococcus aureus Types 5 and 8, components of novel glycoconjugate vaccines. Carbohydr Res 340:1097–1106 [View Article][PubMed]
    [Google Scholar]
  17. Kang M., Ko Y. P., Liang X., Ross C. L., Liu Q., Murray B. E., Höök M. 2013; Collagen-binding microbial surface components recognizing adhesive matrix molecule (MSCRAMM) of Gram-positive bacteria inhibit complement activation via the classical pathway. J Biol Chem 288:20520–20531 [View Article][PubMed]
    [Google Scholar]
  18. Kinoshita T., Takata Y., Kozono H., Takeda J., Hong K. S., Inoue K. 1988; C5 convertase of the alternative complement pathway: covalent linkage between two C3b molecules within the trimolecular complex enzyme. J Immunol 141:3895–3901[PubMed]
    [Google Scholar]
  19. Ko Y. P., Liang X., Smith C. W., Degen J. L., Höök M. 2011; Binding of Efb from Staphylococcus aureus to fibrinogen blocks neutrophil adherence. J Biol Chem 286:9865–9874 [View Article][PubMed]
    [Google Scholar]
  20. Ko Y. P., Kuipers A., Freitag C. M., Jongerius I., Medina E., van Rooijen W. J., Spaan A. N., van Kessel K. P., Höök M. et al. 2013; Phagocytosis escape by a Staphylococcus aureus protein that connects complement and coagulation proteins at the bacterial surface. PLoS Pathog 9:e1003816 [View Article][PubMed]
    [Google Scholar]
  21. Lattar S. M., Noto Llana M., Denoël P., Germain S., Buzzola F. R., Lee J. C., Sordelli D. O. 2014; Protein antigens increase the protective efficacy of a capsule-based vaccine against Staphylococcus aureus in a rat model of osteomyelitis. Infect Immun 82:83–91 [View Article][PubMed]
    [Google Scholar]
  22. Lee J. C., Liu M. J., Parsonnet J., Arbeit R. D. 1990; Expression of type 8 capsular polysaccharide and production of toxic shock syndrome toxin 1 are associated among vaginal isolates of Staphylococcus aureus . J Clin Microbiol 28:2612–2615[PubMed]
    [Google Scholar]
  23. Levy J., Licini L., Haelterman E., Moris P., Lestrate P., Damaso S., Van Belle P., Boutriau D. 2015; Safety and immunogenicity of an investigational 4-component Staphylococcus aureus vaccine with or without AS03B adjuvant: Results of a randomized phase I trial. Hum Vaccin Immunother 11:620–631 [View Article][PubMed]
    [Google Scholar]
  24. Lowy F. D. 1998; Staphylococcus aureus infections. N Engl J Med 339:520–532 [View Article][PubMed]
    [Google Scholar]
  25. Nemeth J., Lee J. C. 1995; Antibodies to capsular polysaccharides are not protective against experimental Staphylococcus aureus endocarditis. Infect Immun 63:375–380[PubMed]
    [Google Scholar]
  26. Nilsson I. M., Lee J. C., Bremell T., Rydén C., Tarkowski A. 1997; The role of staphylococcal polysaccharide microcapsule expression in septicemia and septic arthritis. Infect Immun 65:4216–4221[PubMed]
    [Google Scholar]
  27. Nissen M., Marshall H., Richmond P., Shakib S., Jiang Q., Cooper D., Rill D., Baber J., Eiden J. et al. 2015; A randomized phase I study of the safety and immunogenicity of three ascending dose levels of a 3-antigen Staphylococcus aureus vaccine (SA3Ag) in healthy adults. Vaccine 33:1846–1854 [View Article][PubMed]
    [Google Scholar]
  28. O'Riordan K., Lee J. C. 2004; Staphylococcus aureus capsular polysaccharides. Clin Microbiol Rev 17:218–234[PubMed] [CrossRef]
    [Google Scholar]
  29. Otto M. 2013; Community-associated MRSA: what makes them special?. IJMM 303:324–330 [View Article][PubMed]
    [Google Scholar]
  30. Palma M., Nozohoor S., Schennings T., Heimdahl A., Flock J. I. 1996; Lack of the extracellular 19-kilodalton fibrinogen-binding protein from Staphylococcus aureus decreases virulence in experimental wound infection. Infect Immun 64:5284–5289[PubMed]
    [Google Scholar]
  31. Pang Y. Y., Schwartz J., Thoendel M., Ackermann L. W., Horswill A. R., Nauseef W. M. 2010; agr-Dependent interactions of Staphylococcus aureus USA300 with human polymorphonuclear neutrophils. J Innate Immun 2:546–559 [View Article][PubMed]
    [Google Scholar]
  32. Park S., Gerber S., Lee J. C. 2014; Antibodies to Staphylococcus aureus serotype 8 capsular polysaccharide react with and protect against serotype 5 and 8 isolates. Infect Immun 82:5049–5055 [View Article][PubMed]
    [Google Scholar]
  33. Pöhlmann-Dietze P., Ulrich M., Kiser K. B., Döring G., Lee J. C., Fournier J. M., Botzenhart K., Wolz C. 2000; Adherence of Staphylococcus aureus to endothelial cells: influence of capsular polysaccharide, global regulator agr, and bacterial growth phase. Infect Immun 68:4865–4871[PubMed] [CrossRef]
    [Google Scholar]
  34. Ricklin D., Hajishengallis G., Yang K., Lambris J. D. 2010; Complement: a key system for immune surveillance and homeostasis. Nat Immunol 11:785–797 [View Article][PubMed]
    [Google Scholar]
  35. Rossolini G. M., Arena F., Pecile P., Pollini S. 2014; Update on the antibiotic resistance crisis. Curr Opin Pharmacol 18:56–60 [View Article][PubMed]
    [Google Scholar]
  36. Schenk S., Laddaga R. A. 1992; Improved method for electroporation of Staphylococcus aureus . FEMS Microbiol Lett 73:133–138[PubMed] [CrossRef]
    [Google Scholar]
  37. Shannon O., Uekotter A., Flock J. 2005; Extracellular fibrinogen binding protein Efb from Staphylococcus aureus as an antiplatelet agent in vivo. Thromb Haemost1–5
    [Google Scholar]
  38. Slot J. W., Geuze H. J. 2007; Cryosectioning and immunolabeling. Nat Protoc 2:2480–2491 [View Article][PubMed]
    [Google Scholar]
  39. Sompolinsky D., Samra Z., Karakawa W. W., Vann W. F., Schneerson R., Malik Z. 1985; Encapsulation and capsular types in isolates of Staphylococcus aureus from different sources and relationship to phage types. J Clin Microbiol 22:828–834[PubMed]
    [Google Scholar]
  40. Stemerding A. M., Köhl J., Pandey M. K., Kuipers A., Leusen J. H., Boross P., Nederend M., Vidarsson G., Weersink A. Y. et al. 2013; Staphylococcus aureus formyl peptide receptor-like 1 inhibitor (FLIPr) and its homologue FLIPr-like are potent FcγR antagonists that inhibit IgG-mediated effector functions. J Immunol 191:353–362 [View Article][PubMed]
    [Google Scholar]
  41. Thakker M., Park J. S., Carey V., Lee J. C. 1998; Staphylococcus aureus serotype 5 capsular polysaccharide is antiphagocytic and enhances bacterial virulence in a murine bacteremia model. Infect Immun 66:5183–5189[PubMed]
    [Google Scholar]
  42. Tong S. Y., Davis J. S., Eichenberger E., Holland T. L., Fowler V. G. 2015; Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. Clin Microbiol Rev 28:603–661 [View Article][PubMed]
    [Google Scholar]
  43. van Kessel K. P., Bestebroer J., van Strijp J. A. 2014; Neutrophil-mediated phagocytosis of staphylococcus aureus . Front Immunol 5:467 [View Article][PubMed]
    [Google Scholar]
  44. Voyich J. M., Vuong C., DeWald M., Nygaard T. K., Kocianova S., Griffith S., Jones J., Iverson C., Sturdevant D. E. et al. 2009; The SaeR/S gene regulatory system is essential for innate immune evasion by Staphylococcus aureus . J Infect Dis 199:1698–1706 [View Article][PubMed]
    [Google Scholar]
  45. Vuong C., Yeh A. J., Cheung G. Y., Otto M. 2015; Investigational drugs to treat methicillin-resistant Staphylococcus aureus . Expert Opin Investig Drugs 3784:73–93
    [Google Scholar]
  46. Wacker M., Wang L., Kowarik M., Dowd M., Lipowsky G., Faridmoayer A., Shields K., Park S., Alaimo C. et al. 2014; Prevention of Staphylococcus aureus infections by glycoprotein vaccines synthesized in Escherichia coli . J Infect Dis 209:1551–1561 [View Article][PubMed]
    [Google Scholar]
  47. Watts A., Ke D., Wang Q., Pillay A., Nicholson-Weller A., Lee J. C. 2005; Staphylococcus aureus strains that express serotype 5 or serotype 8 capsular polysaccharides differ in virulence. Infect Immun 73:3502–3511 [View Article][PubMed]
    [Google Scholar]
  48. Wilkinson B. J., Sisson S. P., Kim Y., Peterson P. K. 1979; Localization of the third component of complement on the cell wall of encapsulated Staphylococcus aureus M: implications for the mechanism of resistance to phagocytosis . Infect Immun 26:1159–1163[PubMed]
    [Google Scholar]
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