The contribution of group A streptococcal virulence determinants to the pathogenesis of sepsis

Virulence

Volumn 5, Issue 1, 2014, Pages 127-136

  Reglinski, Mark ^a   Sriskandan, Shiranee ^a  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

Group A streptococcus; Sepsis; STSS; Superantigen; Toxic shock syndrome

Indexed keywords

FIBRINOGEN; GLUTATHIONE TRANSFERASE M1; SUPERANTIGEN; T LYMPHOCYTE RECEPTOR; THROMBOPLASTIN; TOLL LIKE RECEPTOR; TOXIC SHOCK SYNDROME TOXIN 1; VIRULENCE FACTOR;

ANTIBIOTIC SENSITIVITY; ANTIGEN BINDING; BACTERIAL VIRULENCE; CELLULAR IMMUNITY; DISEASE ASSOCIATION; DISEASE CONTROL; DISEASE COURSE; DISSEMINATED INTRAVASCULAR CLOTTING; HUMAN; IMMUNE RESPONSE; MORBIDITY; NONHUMAN; PATHOGENESIS; PREVALENCE; REVIEW; SEPSIS; SEPTIC SHOCK; STAPHYLOCOCCUS AUREUS; STREPTOCOCCUS GROUP A; TOXIC SHOCK SYNDROME;

GROUP A STREPTOCOCCUS; SEPSIS; STSS; SUPERANTIGEN; TOXIC SHOCK SYNDROME;

BLOOD COAGULATION; HUMANS; INFLAMMATION; SHOCK, SEPTIC; STREPTOCOCCAL INFECTIONS; STREPTOCOCCUS PYOGENES; SUPERANTIGENS; TOLL-LIKE RECEPTORS; VIRULENCE FACTORS;

EID: 84891656127     PISSN: 21505594     EISSN: 21505608     Source Type: Journal    
DOI: 10.4161/viru.26400     Document Type: Review

References (115)

1. Jacobs ER, Bone RC. Clinical indicators in sepsis and septic adult respiratory distress syndrome. Med Clin North Am 1986; 70:921-932; PMID:3520186
2. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ; ACCP/SCCM Consensus Conference Committee. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. 1992. Chest 2009; 136(Suppl):e28; PMID:20162763
3. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G; International Sepsis Definitions Conference. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med 2003; 29:530-538; PMID:12664219; http://dx.doi.org/10.1007/s00134-003-1662-x
4. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, et al.; Surviving Sepsis Campaign Guidelines Committee including The Pediatric Subgroup. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 2013; 39:165-228; PMID:23361625; http://dx.doi.org/10.1007/s00134-012-2769-8
5. Breiman RF, Davis JP, Facklam RR, et al.; The Working Group on Severe Streptococcal Infections. Defining the group A streptococcal toxic shock syndrome. Rationale and consensus definition. JAMA 1993; 269:390-391; PMID:8418347; http://dx.doi.org/10.1001/jama.1993.03500030088038
6. Lamagni TL, Darenberg J, Luca-Harari B, Siljander T, Efstratiou A, Henriques-Normark B, Vuopio-Varkila J, Bouvet A, Creti R, Ekelund K, et al.; Strep-EURO Study Group. Epidemiology of severe Streptococcus pyogenes disease in Europe. J Clin Microbiol 2008; 46:2359-2367; PMID:18463210; http://dx.doi.org/10.1128/JCM.00422-08
7. O'Loughlin RE, Roberson A, Cieslak PR, Lynfield R, Gershman K, Craig A, Albanese BA, Farley MM, Barrett NL, Spina NL, et al.; Active Bacterial Core Surveillance Team. The epidemiology of invasive group A streptococcal infection and potential vaccine implications: United States, 2000-2004. Clin Infect Dis 2007; 45:853-862; PMID:17806049; http://dx.doi.org/10.1086/521264
8. Luca-Harari B, Darenberg J, Neal S, Siljander T, Strakova L, Tanna A, Creti R, Ekelund K, Koliou M, Tassios PT, et al.; Strep-EURO Study Group. Clinical and microbiological characteristics of severe Streptococcus pyogenes disease in Europe. J Clin Microbiol 2009; 47:1155-1165; PMID:19158266; http://dx.doi.org/10.1128/JCM.02155-08
9. Aziz RK, Kotb M. Rise and persistence of global M1T1 clone of Streptococcus pyogenes. Emerg Infect Dis 2008; 14:1511-1517; PMID:18826812; http://dx.doi.org/10.3201/eid1410.071660
10. Cole JN, Barnett TC, Nizet V, Walker MJ. Molecular insight into invasive group A streptococcal disease. Nat Rev Microbiol 2011; 9:724-736; PMID:21921933; http://dx.doi.org/10.1038/nrmicro2648
11. Sumby P, Whitney AR, Graviss EA, DeLeo FR, Musser JM. Genome-wide analysis of group a streptococci reveals a mutation that modulates global phenotype and disease specificity. PLoS Pathog 2006; 2:e5; PMID:16446783; http://dx.doi.org/10.1371/journal.ppat.0020005
12. Sumby P, Porcella SF, Madrigal AG, Barbian KD, Virtaneva K, Ricklefs SM, Sturdevant DE, Graham MR, Vuopio-Varkila J, Hoe NP, et al. Evolutionary origin and emergence of a highly successful clone of serotype M1 group a Streptococcus involved multiple horizontal gene transfer events. J Infect Dis 2005; 192:771-782; PMID:16088826; http://dx.doi.org/10.1086/432514
13. Rantala S, Vähäkuopus S, Siljander T, Vuopio J, Huhtala H, Vuento R, Syrjänen J. Streptococcus pyogenes bacteraemia, emm types and superantigen profiles. Eur J Clin Microbiol Infect Dis 2012; 31:859-865; PMID:21877175; http://dx.doi.org/10.1007/s10096-011-1385-9
14. Michaelsen TE, Andreasson IK, Langerud BK, Caugant DA. Similar superantigen gene profiles and superantigen activity in norwegian isolates of invasive and non-invasive group a streptococci. Scand J Immunol 2011; 74:423-429; PMID:21707691; http://dx.doi.org/10.1111/j.1365-3083.2011.02594.x
15. Maripuu L, Eriksson A, Norgren M. Superantigen gene profile diversity among clinical group A streptococcal isolates. FEMS Immunol Med Microbiol 2008; 54:236-44; PMID:18754783; http://dx.doi.org/10.1111/j.1574-695X.2008.00469.x
16. Graham MR, Smoot LM, Migliaccio CA, Virtaneva K, Sturdevant DE, Porcella SF, Federle MJ, Adams GJ, Scott JR, Musser JM. Virulence control in group A Streptococcus by a two-component gene regulatory system: global expression profiling and in vivo infection modeling. Proc Natl Acad Sci U S A 2002; 99:13855-13860; PMID:12370433; http://dx.doi.org/10.1073/pnas.202353699
17. Treviño J, Perez N, Ramirez-Peña E, Liu Z, Shelburne SA 3rd, Musser JM, Sumby P. CovS simultaneously activates and inhibits the CovR-mediated repression of distinct subsets of group A Streptococcus virulence factor-encoding genes. Infect Immun 2009; 77:3141-3149; PMID:19451242; http://dx.doi.org/10.1128/IAI.01560-08
18. Heath A, DiRita VJ, Barg NL, Engleberg NC. A twocomponent regulatory system, CsrR-CsrS, represses expression of three Streptococcus pyogenes virulence factors, hyaluronic acid capsule, streptolysin S, and pyrogenic exotoxin B. Infect Immun 1999; 67:5298-5305; PMID:10496909
19. Turner CE, Kurupati P, Jones MD, Edwards RJ, Sriskandan S. Emerging role of the interleukin-8 cleaving enzyme SpyCEP in clinical Streptococcus pyogenes infection. J Infect Dis 2009; 200:555-563; PMID:19591574; http://dx.doi.org/10.1086/603541
20. Kurupati P, Turner CE, Tziona I, Lawrenson RA, Alam FM, Nohadani M, Stamp GW, Zinkernagel AS, Nizet V, Edwards RJ, et al. Chemokine-cleaving Streptococcus pyogenes protease SpyCEP is necessary and sufficient for bacterial dissemination within soft tissues and the respiratory tract. Mol Microbiol 2010; 76:1387-1397; PMID:20158613; http://dx.doi.org/10.1111/j.1365-2958.2010.07065.x
21. Levin JC, Wessels MR. Identification of csrR/csrS, a genetic locus that regulates hyaluronic acid capsule synthesis in group A Streptococcus. Mol Microbiol 1998; 30:209-219; PMID:9786197; http://dx.doi.org/10.1046/j.1365-2958.1998.01057.x
22. Olsen RJ, Sitkiewicz I, Ayeras AA, Gonulal VE, Cantu C, Beres SB, Green NM, Lei B, Humbird T, Greaver J, et al. Decreased necrotizing fasciitis capacity caused by a single nucleotide mutation that alters a multiple gene virulence axis. Proc Natl Acad Sci U S A 2010; 107:888-893; PMID:20080771; http://dx.doi.org/10.1073/pnas.0911811107
23. Herwald H, Collin M, Müller-Esterl W, Björck L. Streptococcal cysteine proteinase releases kinins: a virulence mechanism. J Exp Med 1996; 184:665-673; PMID:8760820; http://dx.doi.org/10.1084/jem.184.2.665
24. Kapur V, Majesky MW, Li LL, Black RA, Musser JM. Cleavage of interleukin 1 beta (IL-1 beta) precursor to produce active IL-1 beta by a conserved extracellular cysteine protease from Streptococcus pyogenes. Proc Natl Acad Sci U S A 1993; 90:7676-7680; PMID:7689226; http://dx.doi.org/10.1073/pnas.90.16.7676
25. Maamary PG, Sanderson-Smith ML, Aziz RK, Hollands A, Cole JN, McKay FC, McArthur JD, Kirk JK, Cork AJ, Keefe RJ, et al. Parameters governing invasive disease propensity of non-M1 serotype group A streptococci. J Innate Immun 2010; 2:596-606; PMID:20814186; http://dx.doi.org/10.1159/000317640
26. Ikebe T, Ato M, Matsumura T, Hasegawa H, Sata T, Kobayashi K, Watanabe H. Highly frequent mutations in negative regulators of multiple virulence genes in group A streptococcal toxic shock syndrome isolates. PLoS Pathog 2010; 6:e1000832; PMID:20368967; http://dx.doi.org/10.1371/journal.ppat.1000832
27. Renné T. The procoagulant and proinflammatory plasma contact system. Semin Immunopathol 2012; 34:31-41; PMID:21858560; http://dx.doi.org/10.1007/s00281-011-0288-2
28. Shannon O, Herwald H, Oehmcke S. Modulation of the coagulation system during severe streptococcal disease. Curr Top Microbiol Immunol 2013; 368:189-205; PMID:23224709; http://dx.doi.org/10.1007/82_2012_283
29. McMichael M. New models of hemostasis. Top Companion Anim Med 2012; 27:40-45; PMID:23031454; http://dx.doi.org/10.1053/j.tcam.2012.07.005
30. Påhlman LI, Malmström E, Mörgelin M, Herwald H. M protein from Streptococcus pyogenes induces tissue factor expression and pro-coagulant activity in human monocytes. Microbiology 2007; 153:2458-2464; PMID:17660410; http://dx.doi.org/10.1099/mic.0.2006/003285-0
31. Ashbaugh CD, Warren HB, Carey VJ, Wessels MR. Molecular analysis of the role of the group A streptococcal cysteine protease, hyaluronic acid capsule, and M protein in a murine model of human invasive soft-tissue infection. J Clin Invest 1998; 102:550-560; PMID:9691092; http://dx.doi.org/10.1172/JCI3065
32. Gawaz M, Dickfeld T, Bogner C, Fateh-Moghadam S, Neumann FJ. Platelet function in septic multiple organ dysfunction syndrome. Intensive Care Med 1997; 23:379-385; PMID:9142575; http://dx.doi.org/10.1007/s001340050344
33. Gustot T. Multiple organ failure in sepsis: prognosis and role of systemic inflammatory response. Curr Opin Crit Care 2011; 17:153-159; PMID:21346564; http://dx.doi.org/10.1097/MCC.0b013e328344b446
34. Sjöbring U, Ringdahl U, Ruggeri ZM. Induction of platelet thrombi by bacteria and antibodies. Blood 2002; 100:4470-4477; PMID:12393652; http://dx.doi.org/10.1182/blood-2002-01-0069
35. Huizinga EG, Tsuji S, Romijn RA, Schiphorst ME, de Groot PG, Sixma JJ, Gros P. Structures of glycoprotein Ibalpha and its complex with von Willebrand factor A1 domain. Science 2002; 297:1176-1179; PMID:12183630; http://dx.doi.org/10.1126/science.107355
36. Reininger AJ, Heijnen HF, Schumann H, Specht HM, Schramm W, Ruggeri ZM. Mechanism of platelet adhesion to von Willebrand factor and microparticle formation under high shear stress. Blood 2006; 107:3537-3545; PMID:16449527; http://dx.doi.org/10.1182/blood-2005-02-0618
37. Shannon O, Hertzén E, Norrby-Teglund A, Mörgelin M, Sjöbring U, Björck L. Severe streptococcal infection is associated with M protein-induced platelet activation and thrombus formation. Mol Microbiol 2007; 65:1147-1157; PMID:17662041; http://dx.doi.org/10.1111/j.1365-2958.2007.05841.x
38. Macheboeuf P, Buffalo C, Fu CY, Zinkernagel AS, Cole JN, Johnson JE, Nizet V, Ghosh P. Streptococcal M1 protein constructs a pathological host fibrinogen network. Nature 2011; 472:64-68; PMID:21475196; http://dx.doi.org/10.1038/nature09967
39. Herwald H, Cramer H, Mörgelin M, Russell W, Sollenberg U, Norrby-Teglund A, Flodgaard H, Lindbom L, Björck L. M protein, a classical bacterial virulence determinant, forms complexes with fibrinogen that induce vascular leakage. Cell 2004; 116:367-379; PMID:15016372; http://dx.doi.org/10.1016/S0092-8674(04)00057-1
40. Gando S, Nanzaki S, Sasaki S, Aoi K, Kemmotsu O. Activation of the extrinsic coagulation pathway in patients with severe sepsis and septic shock. Crit Care Med 1998; 26:2005-2009; PMID:9875912; http://dx.doi.org/10.1097/00003246-199812000-00030
41. Gando S, Kameue T, Nanzaki S, Hayakawa T, Nakanishi Y. Participation of tissue factor and thrombin in posttraumatic systemic inflammatory syndrome. Crit Care Med 1997; 25:1820-1826; PMID:9366764; http://dx.doi.org/10.1097/00003246-199711000-00019
42. Gando S, Nanzaki S, Morimoto Y, Ishitani T, Kemmotsu O. Tissue factor pathway inhibitor response does not correlate with tissue factor-induced disseminated intravascular coagulation and multiple organ dysfunction syndrome in trauma patients. Crit Care Med 2001; 29:262-266; PMID:11246303; http://dx.doi.org/10.1097/00003246-200102000-00006
43. Stief TW, Ijagha O, Weiste B, Herzum I, Renz H, Max M. Analysis of hemostasis alterations in sepsis. Blood Coagul Fibrinolysis 2007; 18:179-186; PMID:17287636; http://dx.doi.org/10.1097/MBC.0b013e328040bf9a
44. Bryant AE, Hayes-Schroer SM, Stevens DL. M type 1 and 3 group A streptococci stimulate tissue factormediated procoagulant activity in human monocytes and endothelial cells. Infect Immun 2003; 71:1903-1910; PMID:12654807; http://dx.doi.org/10.1128/IAI.71.4.1903-1910.2003
45. Oehmcke S, Mörgelin M, Malmström J, Linder A, Chew M, Thorlacius H, Herwald H. Stimulation of blood mononuclear cells with bacterial virulence factors leads to the release of pro-coagulant and pro-inflammatory microparticles. Cell Microbiol 2012; 14:107-119; PMID:21951918; http://dx.doi.org/10.1111/j.1462-5822.2011.01705.x
46. Egorina EM, Sovershaev MA, Hansen JB. The role of tissue factor in systemic inflammatory response syndrome. Blood Coagul Fibrinolysis 2011; 22:451-456; PMID:21597365; http://dx.doi.org/10.1097/MBC.0b013e328346ef3f
47. Leeb-Lundberg LM, Marceau F, Müller-Esterl W, Pettibone DJ, Zuraw BL. International union of pharmacology. XLV. Classification of the kinin receptor family: from molecular mechanisms to pathophysiological consequences. Pharmacol Rev 2005; 57:27-77; PMID:15734727; http://dx.doi.org/10.1124/pr.57.1.2
48. Bengtson SH, Sandén C, Mörgelin M, Marx PF, Olin AI, Leeb-Lundberg LM, Meijers JC, Herwald H. Activation of TAFI on the surface of Streptococcus pyogenes evokes inflammatory reactions by modulating the kallikrein/kinin system. J Innate Immun 2009; 1:18-28; PMID:20375563; http://dx.doi.org/10.1159/000145543
49. Ben Nasr A, Herwald H, Sjöbring U, Renné T, Müller-Esterl W, Björck L. Absorption of kininogen from human plasma by Streptococcus pyogenes is followed by the release of bradykinin. Biochem J 1997; 326:657-660; PMID:9307013
50. Sriskandan S, Kemball-Cook G, Moyes D, Canvin J, Tuddenham E, Cohen J. Contact activation in shock caused by invasive group A Streptococcus pyogenes. Crit Care Med 2000; 28:3684-3691; PMID:11098974; http://dx.doi.org/10.1097/00003246-200011000-00025
51. Linder A, Johansson L, Thulin P, Hertzén E, Mörgelin M, Christensson B, Björck L, Norrby-Teglund A, Akesson P. Erysipelas caused by group A streptococcus activates the contact system and induces the release of heparin-binding protein. J Invest Dermatol 2010; 130:1365-1372; PMID:20107486; http://dx.doi.org/10.1038/jid.2009.437
52. Sriskandan S, Cohen J. Kallikrein-kinin system activation in streptococcal toxic shock syndrome. Clin Infect Dis 2000; 30:961-962; PMID:10880316; http://dx.doi.org/10.1086/313827
53. Murphy K, Travers P, Walport M, Janeway C. Janeway's immunobiology. New York: Garland Science, 2008.
54. Proft T, Fraser JD. Bacterial superantigens. Clin Exp Immunol 2003; 133:299-306; PMID:12930353; http://dx.doi.org/10.1046/j.1365-2249.2003.02203.x
55. Spaulding AR, Salgado-Pabón W, Kohler PL, Horswill AR, Leung DY, Schlievert PM. Staphylococcal and streptococcal superantigen exotoxins. Clin Microbiol Rev 2013; 26:422-447; PMID:23824366; http://dx.doi.org/10.1128/CMR.00104-12
56. Bisno AL, Stevens DL. Streptococcal infections of skin and soft tissues. N Engl J Med 1996; 334:240-245; PMID:8532002; http://dx.doi.org/10.1056/NEJM199601253340407
57. Shah SS, Hall M, Srivastava R, Subramony A, Levin JE. Intravenous immunoglobulin in children with streptococcal toxic shock syndrome. Clin Infect Dis 2009; 49:1369-1376; PMID:19788359; http://dx.doi.org/10.1086/606048
58. Arad G, Levy R, Nasie I, Hillman D, Rotfogel Z, Barash U, Supper E, Shpilka T, Minis A, Kaempfer R. Binding of superantigen toxins into the CD28 homodimer interface is essential for induction of cytokine genes that mediate lethal shock. PLoS Biol 2011; 9:e1001149; PMID:21931534; http://dx.doi.org/10.1371/journal.pbio.1001149
59. Fraser JD, Proft T. The bacterial superantigen and superantigen-like proteins. Immunol Rev 2008; 225:226-243; PMID:18837785; http://dx.doi.org/10.1111/j.1600-065X.2008.00681.x
60. Li Y, Li H, Dimasi N, McCormick JK, Martin R, Schuck P, Schlievert PM, Mariuzza RA. Crystal structure of a superantigen bound to the high-affinity, zinc-dependent site on MHC class II. Immunity 2001; 14:93-104; PMID:11163233; http://dx.doi.org/10.1016/S1074-7613(01)00092-9
61. Fernández MM, Guan R, Swaminathan CP, Malchiodi EL, Mariuzza RA. Crystal structure of staphylococcal enterotoxin I (SEI) in complex with a human major histocompatibility complex class II molecule. J Biol Chem 2006; 281:25356-25364; PMID:16829512; http://dx.doi.org/10.1074/jbc.M603969200
62. Baker MD, Gendlina I, Collins CM, Acharya KR. Crystal structure of a dimeric form of streptococcal pyrogenic exotoxin A (SpeA1). Protein Sci 2004; 13:2285-2290; PMID:15295110; http://dx.doi.org/10.1110/ps.04826804
63. Roussel A, Anderson BF, Baker HM, Fraser JD, Baker EN. Crystal structure of the streptococcal superantigen SPE-C: dimerization and zinc binding suggest a novel mode of interaction with MHC class II molecules. Nat Struct Biol 1997; 4:635-643; PMID:9253413; http://dx.doi.org/10.1038/nsb0897-635
64. Tripp TJ, McCormick JK, Webb JM, Schlievert PM. The zinc-dependent major histocompatibility complex class II binding site of streptococcal pyrogenic exotoxin C is critical for maximal superantigen function and toxic activity. Infect Immun 2003; 71:1548-1550; PMID:12595474; http://dx.doi.org/10.1128/IAI.71.3.1548-1550.2003
65. Swietnicki W, Barnie AM, Dyas BK, Ulrich RG. Zinc binding and dimerization of Streptococcus pyogenes pyrogenic exotoxin C are not essential for T-cell stimulation. J Biol Chem 2003; 278:9885-9895; PMID:12473669; http://dx.doi.org/10.1074/jbc.M206957200
66. Cunningham MW. Pathogenesis of group A streptococcal infections. Clin Microbiol Rev 2000; 13:470-511; PMID:10885988; http://dx.doi.org/10.1128/CMR.13.3.470-511.2000
67. Faulkner L, Cooper A, Fantino C, Altmann DM, Sriskandan S. The mechanism of superantigen-mediated toxic shock: not a simple Th1 cytokine storm. J Immunol 2005; 175:6870-6877; PMID:16272345
68. Litton MJ, Sander B, Murphy E, O'Garra A, Abrams JS. Early expression of cytokines in lymph nodes after treatment in vivo with Staphylococcus enterotoxin B. J Immunol Methods 1994; 175:47-58; PMID:7930639; http://dx.doi.org/10.1016/0022-1759(94)90330-1
69. Commons R, Rogers S, Gooding T, Danchin M, Carapetis J, Robins-Browne R, Curtis N. Superantigen genes in group A streptococcal isolates and their relationship with emm types. J Med Microbiol 2008; 57:1238-1246; PMID:18809552; http://dx.doi.org/10.1099/jmm.0.2008/001156-0
70. Kim YB, Watson DW. A purified group A streptococcal pyrogenic exotoxin. Physiochemical and biological properties including the enhancement of susceptibility to endotoxin lethal shock. J Exp Med 1970; 131:611-622; PMID:4905084; http://dx.doi.org/10.1084/jem.131.3.611
71. Hopkins PA, Fraser JD, Pridmore AC, Russell HH, Read RC, Sriskandan S. Superantigen recognition by HLA class II on monocytes up-regulates toll-like receptor 4 and enhances proinflammatory responses to endotoxin. Blood 2005; 105:3655-3662; PMID:15644417; http://dx.doi.org/10.1182/blood-2004-07-2523
72. Hopkins PA, Pridmore AC, Ellmerich S, Fraser JD, Russell HH, Read RC, Sriskandan S. Increased surface toll-like receptor 2 expression in superantigen shock. Crit Care Med 2008; 36:1267-1276; PMID:18379254; http://dx.doi.org/10.1097/CCM.0b013e31816a0a78
73. Gao H, Leaver SK, Burke-Gaffney A, Finney SJ. Severe sepsis and Toll-like receptors. Semin Immunopathol 2008; 30:29-40; PMID:18071706; http://dx.doi.org/10.1007/s00281-007-0101-4
74. Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol 2004; 4:499-511; PMID:15229469; http://dx.doi.org/10.1038/nri1391
75. Härter L, Mica L, Stocker R, Trentz O, Keel M. Increased expression of toll-like receptor-2 and -4 on leukocytes from patients with sepsis. Shock 2004; 22:403-409; PMID:15489631; http://dx.doi.org/10.1097/01.shk.0000142256.23382.5d
76. Armstrong L, Medford AR, Hunter KJ, Uppington KM, Millar AB. Differential expression of Tolllike receptor (TLR)-2 and TLR-4 on monocytes in human sepsis. Clin Exp Immunol 2004; 136:312-319; PMID:15086396; http://dx.doi.org/10.1111/j.1365-2249.2004.02433.x
77. Brosnahan AJ, Schlievert PM. Gram-positive bacterial superantigen outside-in signaling causes toxic shock syndrome. FEBS J 2011; 278:4649-4667; PMID:21535475; http://dx.doi.org/10.1111/j.1742-4658.2011.08151.x
78. Brosnahan AJ, Schaefers MM, Amundson WH, Mantz MJ, Squier CA, Peterson ML, Schlievert PM. Novel toxic shock syndrome toxin-1 amino acids required for biological activity. Biochemistry 2008; 47:12995-13003; PMID:19012411; http://dx.doi.org/10.1021/bi801468w
79. Peterson ML, Ault K, Kremer MJ, Klingelhutz AJ, Davis CC, Squier CA, Schlievert PM. The innate immune system is activated by stimulation of vaginal epithelial cells with Staphylococcus aureus and toxic shock syndrome toxin 1. Infect Immun 2005; 73:2164-2174; PMID:15784559; http://dx.doi.org/10.1128/IAI.73.4.2164-2174.2005
80. Lee PK, Schlievert PM. Quantification and toxicity of group A streptococcal pyrogenic exotoxins in an animal model of toxic shock syndrome-like illness. J Clin Microbiol 1989; 27:1890-1892; PMID:2504778
81. Unnikrishnan M, Altmann DM, Proft T, Wahid F, Cohen J, Fraser JD, Sriskandan S. The bacterial superantigen streptococcal mitogenic exotoxin Z is the major immunoactive agent of Streptococcus pyogenes. J Immunol 2002; 169:2561-2569; PMID:12193726
82. Kamezawa Y, Nakahara T, Nakano S, Abe Y, Nozaki-Renard J, Isono T. Streptococcal mitogenic exotoxin Z, a novel acidic superantigenic toxin produced by a T1 strain of Streptococcus pyogenes. Infect Immun 1997; 65:3828-3833; PMID:9284159
83. Sriskandan S, Unnikrishnan M, Krausz T, Cohen J. Molecular analysis of the role of streptococcal pyrogenic Exotoxin A (SPEA) in invasive soft-tissue infection resulting from Streptococcus pyogenes. Mol Microbiol 1999; 33:778-790; PMID:10447887; http://dx.doi.org/10.1046/j.1365-2958.1999.01525.x
84. Broudy TB, Pancholi V, Fischetti VA. The in vitro interaction of Streptococcus pyogenes with human pharyngeal cells induces a phage-encoded extracellular DNase. Infect Immun 2002; 70:2805-2811; PMID:12010966; http://dx.doi.org/10.1128/IAI.70.6.2805-2811.2002
85. Unnikrishnan M, Cohen J, Sriskandan S. Complementation of a speA negative Streptococcus pyogenes with speA: effects on virulence and production of streptococcal pyrogenic exotoxin A. Microb Pathog 2001; 31:109-114; PMID:11500096; http://dx.doi.org/10.1006/mpat.2001.0453
86. Sriskandan S, Moyes D, Buttery LK, Krausz T, Evans TJ, Polak J, Cohen J. Streptococcal pyrogenic exotoxin A release, distribution, and role in a murine model of fasciitis and multiorgan failure due to Streptococcus pyogenes. J Infect Dis 1996; 173:1399-1407; PMID:8648212; http://dx.doi.org/10.1093/infdis/173.6.1399
87. Sriskandan S, Unnikrishnan M, Krausz T, Dewchand H, Van Noorden S, Cohen J, Altmann DM. Enhanced susceptibility to superantigen-associated streptococcal sepsis in human leukocyte antigen-DQ transgenic mice. J Infect Dis 2001; 184:166-173; PMID:11424013; http://dx.doi.org/10.1086/322018
88. Müller-Alouf H, Proft T, Zollner TM, Gerlach D, Champagne E, Desreumaux P, Fitting C, Geoffroy-Fauvet C, Alouf JE, Cavaillon JM. Pyrogenicity and cytokine-inducing properties of Streptococcus pyogenes superantigens: comparative study of streptococcal mitogenic exotoxin Z and pyrogenic exotoxin A. Infect Immun 2001; 69:4141-4145; PMID:11349089; http://dx.doi.org/10.1128/IAI.69.6.4141-4145.2001
89. Lintges M, van der Linden M, Hilgers RD, Arlt S, Al-Lahham A, Reinert RR, Plücken S, Rink L. Superantigen genes are more important than the emm type for the invasiveness of group A Streptococcus infection. J Infect Dis 2010; 202:20-28; PMID:20497047; http://dx.doi.org/10.1086/653082
90. Proft T, Moffatt SL, Weller KD, Paterson A, Martin D, Fraser JD. The streptococcal superantigen SMEZ exhibits wide allelic variation, mosaic structure, and significant antigenic variation. J Exp Med 2000; 191:1765-1776; PMID:10811869; http://dx.doi.org/10.1084/jem.191.10.1765
91. Turner CE, Sommerlad M, McGregor K, Davies FJ, Pichon B, Chong DL, Farzaneh L, Holden MT, Spratt BG, Efstratiou A, et al. Superantigenic activity of emm3 Streptococcus pyogenes is abrogated by a conserved, naturally occurring smeZ mutation. PLoS One 2012; 7:e46376; PMID:23049698; http://dx.doi.org/10.1371/journal.pone.0046376
92. Michie C, Scott A, Cheesbrough J, Beverley P, Pasvol G. Streptococcal toxic shock-like syndrome: evidence of superantigen activity and its effects on T lymphocyte subsets in vivo. Clin Exp Immunol 1994; 98:140-144; PMID:7923873; http://dx.doi.org/10.1111/j.1365-2249.1994.tb06620.x
93. Watanabe-Ohnishi R, Low DE, McGeer A, Stevens DL, Schlievert PM, Newton D, Schwartz B, Kreiswirth B, Kotb M; Ontario Streptococcal Study Project. Selective depletion of V β-bearing T cells in patients with severe invasive group A streptococcal infections and streptococcal toxic shock syndrome. J Infect Dis 1995; 171:74-84; PMID:7798684; http://dx.doi.org/10.1093/infdis/171.1.74
94. Sriskandan S, Moyes D, Cohen J. Detection of circulating bacterial superantigen and lymphotoxin-alpha in patients with streptococcal toxic-shock syndrome. Lancet 1996; 348:1315-1316; PMID:8909404; http://dx.doi.org/10.1016/S0140-6736(05)65800-X
95. Norrby-Teglund A, Thulin P, Gan BS, Kotb M, McGeer A, Andersson J, Low DE. Evidence for superantigen involvement in severe group a streptococcal tissue infections. J Infect Dis 2001; 184:853-860; PMID:11509997; http://dx.doi.org/10.1086/323443
96. Proft T, Sriskandan S, Yang L, Fraser JD. Superantigens and streptococcal toxic shock syndrome. Emerg Infect Dis 2003; 9:1211-1218; PMID:14609454; http://dx.doi.org/10.3201/eid0910.030042
97. Fast DJ, Schlievert PM, Nelson RD. Nonpurulent response to toxic shock syndrome toxin 1-producing Staphylococcus aureus. Relationship to toxin-stimulated production of tumor necrosis factor. J Immunol 1988; 140:949-953; PMID:3339245
98. Cockerill FR 3rd, Thompson RL, Musser JM, Schlievert PM, Talbot J, Holley KE, Harmsen WS, Ilstrup DM, Kohner PC, Kim MH, et al.; Southeastern Minnesota Streptococcal Working Group. Molecular, serological, and clinical features of 16 consecutive cases of invasive streptococcal disease. Clin Infect Dis 1998; 26:1448-1458; PMID:9636878; http://dx.doi.org/10.1086/516376
99. Davis JP, Chesney PJ, Wand PJ, LaVenture M. Toxicshock syndrome: epidemiologic features, recurrence, risk factors, and prevention. N Engl J Med 1980; 303:1429-1435; PMID:7432401; http://dx.doi.org/10.1056/NEJM198012183032501
100. Ji YD, McLandsborough L, Kondagunta A, Cleary PP. C5a peptidase alters clearance and trafficking of group A streptococci by infected mice. Infect Immun 1996; 64:503-510; PMID:8550199
101. Zinkernagel AS, Timmer AM, Pence MA, Locke JB, Buchanan JT, Turner CE, Mishalian I, Sriskandan S, Hanski E, Nizet V. The IL-8 protease SpyCEP/ScpC of group A Streptococcus promotes resistance to neutrophil killing. Cell Host Microbe 2008; 4:170-178; PMID:18692776; http://dx.doi.org/10.1016/j.chom.2008.07.002
102. Neumann B, Engelhardt B, Wagner H, Holzmann B. Induction of acute inflammatory lung injury by staphylococcal enterotoxin B. J Immunol 1997; 158:1862-1871; PMID:9029127
103. Diener K, Tessier P, Fraser J, Köntgen F, McColl SR. Induction of acute inflammation in vivo by staphylococcal superantigens I: Leukocyte recruitment occurs independently of T lymphocytes and major histocompatibility complex Class II molecules. Lab Invest 1998; 78:647-656; PMID:9645755
104. Tessier PA, Naccache PH, Diener KR, Gladue RP, Neote KS, Clark-Lewis I, McColl SR. Induction of acute inflammation in vivo by staphylococcal superantigens. II. Critical role for chemokines, ICAM-1, and TNF-alpha. J Immunol 1998; 161:1204-1211; PMID:9686580
105. Sriskandan S, Ferguson M, Elliot V, Faulkner L, Cohen J. Human intravenous immunoglobulin for experimental streptococcal toxic shock: bacterial clearance and modulation of inflammation. J Antimicrob Chemother 2006; 58:117-214; PMID:16670109; http://dx.doi.org/10.1093/jac/dkl173
106. Norrby-Teglund A, Nepom GT, Kotb M. Differential presentation of group A streptococcal superantigens by HLA class II DQ and DR alleles. Eur J Immunol 2002; 32:2570-2577; PMID:12207341; http://dx.doi.org/10.1002/1521-4141(200209)32:92570::AIDIMMU25703.0.CO;2-E
107. Kotb M, Norrby-Teglund A, McGeer A, El-Sherbini H, Dorak MT, Khurshid A, Green K, Peeples J, Wade J, Thomson G, et al. An immunogenetic and molecular basis for differences in outcomes of invasive group A streptococcal infections. Nat Med 2002; 8:1398-1404; PMID:12436116; http://dx.doi.org/10.1038/nm1202-800
108. Llewelyn M, Sriskandan S, Peakman M, Ambrozak DR, Douek DC, Kwok WW, Cohen J, Altmann DM. HLA class II polymorphisms determine responses to bacterial superantigens. J Immunol 2004; 172:1719-1726; PMID:14734754
109. Llewelyn M. Human leukocyte antigen class II haplotypes that protect against or predispose to streptococcal toxic shock. Clin Infect Dis 2005; 41(Suppl 7):S445-S448; PMID:16237645; http://dx.doi.org/10.1086/431986
110. Jardetzky TS, Brown JH, Gorga JC, Stern LJ, Urban RG, Chi YI, Stauffacher C, Strominger JL, Wiley DC. Three-dimensional structure of a human class II histocompatibility molecule complexed with superantigen. Nature 1994; 368:711-718; PMID:8152483; http://dx.doi.org/10.1038/368711a0
111. Sundberg E, Jardetzky TS. Structural basis for HLA-DQ binding by the streptococcal superantigen SSA. Nat Struct Biol 1999; 6:123-129; PMID:10048922; http://dx.doi.org/10.1038/5809
112. Nooh MM, Nookala S, Kansal R, Kotb M. Individual genetic variations directly effect polarization of cytokine responses to superantigens associated with streptococcal sepsis: implications for customized patient care. J Immunol 2011; 186:3156-3163; PMID:21282506; http://dx.doi.org/10.4049/jimmunol.1002057
113. Faulkner L, Altmann DM, Ellmerich S, Huhtaniemi I, Stamp G, Sriskandan S. Sexual dimorphism in superantigen shock involves elevated TNF-alpha and TNF-alpha induced hepatic apoptosis. Am J Respir Crit Care Med 2007; 176:473-482; PMID:17575097; http://dx.doi.org/10.1164/rccm.200611-1712OC
114. Norrby-Teglund A, Kaul R, Low DE, McGeer A, Newton DW, Andersson J, Andersson U, Kotb M. Plasma from patients with severe invasive group A streptococcal infections treated with normal polyspecific IgG inhibits streptococcal superantigeninduced T cell proliferation and cytokine production. J Immunol 1996; 156:3057-3064; PMID:8609429
115. Lamagni TL, Neal S, Keshishian C, Powell D, Potz N, Pebody R, George R, Duckworth G, Vuopio-Varkila J, Efstratiou A. Predictors of death after severe Streptococcus pyogenes infection. Emerg Infect Dis 2009; 15:1304-1307; PMID:19751599; http://dx.doi.org/10.3201/eid1508.090264