Staphylococcus aureus α-toxin: Nearly a century of intrigue

Toxins

Volumn 5, Issue 6, 2013, Pages 1140-1166

  Berube, Bryan J ^a   Wardenburg, Juliane Bubeck ^a  

^a UNIVERSITY OF CHICAGO   (United States)

Author keywords

toxin; ADAM10; Cellular responses; Pore forming toxins; S. aureus vaccine and therapeutic; Staphylococcus aureus

Indexed keywords

ADAM10 ENDOPEPTIDASE; STAPHYLOCOCCUS ALPHA TOXIN;

AMINO ACID SEQUENCE; ANTIBODY RESPONSE; ANTIBODY TITER; BACTERIAL METABOLISM; BACTERIUM CULTURE; BACTERIUM ISOLATE; CHANNEL GATING; CIRCULAR DICHROISM; CONFORMATIONAL TRANSITION; CRYSTAL STRUCTURE; CYTOTOXICITY; ENZYME ACTIVATION; GENE LOCUS; HOST PATHOGEN INTERACTION; HUMAN; IMMUNOMODULATION; INNATE IMMUNITY; NONHUMAN; OLIGOMERIZATION; PATHOGENESIS; PROMOTER REGION; PROTEIN EXPRESSION; REVIEW; STAPHYLOCOCCUS AUREUS; STAPHYLOCOCCUS INFECTION; STRUCTURE ACTIVITY RELATION; TISSUE INJURY; TOXIN ANALYSIS; TOXIN STRUCTURE; TOXIN SYNTHESIS;

ANIMALS; ANTIBODIES, BACTERIAL; BACTERIAL TOXINS; HEMOLYSIN PROTEINS; HUMANS; PROTEIN CONFORMATION; STAPHYLOCOCCAL INFECTIONS;

STAPHYLOCOCCUS AUREUS;

EID: 84879131303     PISSN: 20726651     EISSN: None     Source Type: Journal    
DOI: 10.3390/toxins5061140     Document Type: Review

References (177)

1. Bhakdi, S.; Tranum-Jensen, J. Alpha-toxin of Staphylococcus aureus. Microbiol. Rev. 1991, 55, 733-751.
2. Van der Goot, F.G.E. Pore Forming Toxins; Springer Verlag: Berlin, Germany, 2001.
3. Prevost, G.; Mourey, L.; Colin, D.; Monteil, H.; Dalla Serra, M.; Menestrina, G. Alpha-helix and Beta-barrel Pore-forming Toxins (Leucocidins, alpha-, gamma-, and delta-cytolysins) of Staphylococcus aureus. In The Comprehensive Sourcebook of Bacterial Toxins; Alouf, J.E., Freer, J.H., Eds.; Academic Press: London, UK, 2005; pp. 590-607.
4. Parker, M.W.; Feil, S.C. Pore-forming protein toxins: From structure to function. Prog. Biophys. Mol. Biol. 2005, 88, 91-142.
5. Song, L.; Hobaugh, M.R.; Shustak, C.; Cheley, S.; Bayley, H.; Gouaux, J.E. Structure of staphylococcal alpha-hemolysin, a heptameric transmembrane pore. Science 1996, 274, 1859-1866.
6. Gouaux, J.E.; Braha, O.; Hobaugh, M.R.; Song, L.; Cheley, S.; Shustak, C.; Bayley, H. Subunit stoichiometry of staphylococcal alpha-hemolysin in crystals and on membranes: A heptameric transmembrane pore. Proc. Natl. Acad. Sci. USA 1994, 91, 12828-12831.
7. Bhakdi, S.; Walev, I.; Hussmann, M.; Valeva, A. Staphylococcal Alpha-Toxin. In Microbial Protein Toxins; Schmitt, M.J., Schaffrath, R., Eds.; Springer-Verlag: Berlin, Germany, 2005.
8. Haugwitz, U.; Bobkiewicz, W.; Han, S.R.; Beckmann, E.; Veerachato, G.; Shaid, S.; Biehl, S.; Dersch, K.; Bhakdi, S.; Husmann, M. Pore-forming Staphylococcus aureus alpha-toxin triggers epidermal growth factor receptor-dependent proliferation. Cell Microbiol. 2006, 8, 1591-1600.
9. Craven, R.R.; Gao, X.; Allen, I.C.; Gris, D.; Bubeck Wardenburg, J.; McElvania-Tekippe, E.; Ting, J.P.; Duncan, J.A. Staphylococcus aureus alpha-hemolysin activates the nlrp3-inflammasome in human and mouse monocytic cells. PLoS One 2009, 4, e7446.
10. Cho, J.S.; Guo, Y.; Ramos, R.I.; Hebroni, F.; Plaisier, S.B.; Xuan, C.; Granick, J.L.; Matsushima, H.; Takashima, A.; Iwakura, Y. Neutrophil-derived il-1beta is sufficient for abscess formation in immunity against Staphylococcus aureus in mice. PLoS Pathog. 2012, 8, e1003047.
11. Inoshima, I.; Inoshima, N.; Wilke, G.A.; Powers, M.E.; Frank, K.M.; Wang, Y.; Bubeck Wardenburg, J. A Staphylococcus aureus pore-forming toxin subverts the activity of adam10 to cause lethal infection in mice. Nat. Med. 2011, 17, 1310-1314.
12. Inoshima, N.; Wang, Y.; Wardenburg, J.B. Genetic requirement for adam10 in severe Staphylococcus aureus skin infection. J. Invest. Dermatol. 2012, 132, 1513-1516.
13. Powers, M.E.; Kim, H.K.; Wang, Y.; Bubeck Wardenburg, J. Adam10 mediates vascular injury induced by Staphylococcus aureus alpha-hemolysin. J. Infect. Dis. 2012, 206, 352-356.
14. Burnet, F.M. The exotoxins of Staphylococcus pyogenes aureus. J. Pathol. Bacteriol. 1929, 32, 717-734.
15. Burnet, F.M. The production of staphylococcal toxin. J. Pathol. Bacteriol. 1930, 33, 1-16.
16. Cassidy, P.S.; Harshman, S. The binding of staphylococcal 125I-alpha-toxin (b) to erythrocytes. J. Biol. Chem. 1973, 248, 5545-5546.
17. Cassidy, P.; Harshman, S. Studies on the binding of staphylococcal 125I-labeled alpha-toxin to rabbit erythrocytes. Biochemistry 1976, 15, 2348-2355.
18. Hildebrand, A.; Pohl, M.; Bhakdi, S. Staphylococcus aureus alpha-toxin. Dual mechanism of binding to target cells. J. Biol. Chem. 1991, 266, 17195-17200.
19. Siegel, I.; Cohen, S. Action of staphylococcal toxin on human platelets. J. Infect. Dis. 1964, 114, 488-502.
20. Bubeck Wardenburg, J.; Patel, R.J.; Schneewind, O. Surface proteins and exotoxins are required for the pathogenesis of Staphylococcus aureus pneumonia. Infect. Immun. 2007, 75, 1040-1044.
21. Grimminger, F.; Rose, F.; Sibelius, U.; Meinhardt, M.; Potzsch, B.; Spriestersbach, R.; Bhakdi, S.; Suttorp, N.; Seeger, W. Human endothelial cell activation and mediator release in response to the bacterial exotoxins Escherichia coli hemolysin and staphylococcal alpha-toxin. J. Immunol. 1997, 159, 1909-1916.
22. Nygaard, T.K.; Pallister, K.B.; DuMont, A.L.; DeWald, M.; Watkins, R.L.; Pallister, E.Q.; Malone, C.; Griffith, S.; Horswill, A.R.; Torres, V.J. Alpha-toxin induces programmed cell death of human T cells, B cells, and monocytes during USA300 infection. PLoS One 2012, 7, e36532.
23. Manohar, M.; Maheswaran, S.K.; Frommes, S.P.; Lindorfer, R.K. Platelet damaging factor, a fifth activity of staphylococcal alpha-toxin. J. Bacteriol. 1967, 94, 224-231.
24. Bhakdi, S.; Muhly, M.; Mannhardt, U.; Hugo, F.; Klapettek, K.; Mueller-Eckhardt, C.; Roka, L. Staphylococcal alpha toxin promotes blood coagulation via attack on human platelets. J. Exp. Med. 1988, 168, 527-542.
25. Holtfreter, S.; Nguyen, T.T.H.; Wertheim, H.; Steil, L.; Kusch, H.; Truong, Q.P.; Engelmann, S.; Hecker, M.; Volker, U.; van Belkum, A. Human immune proteome in experimental colonization with Staphylococcus aureus. Clin. Vaccine Immunol. 2009, 16, 1607-1614.
26. Kolata, J.; Bode, L.G.; Holtfreter, S.; Steil, L.; Kusch, H.; Holtfreter, B.; Albrecht, D.; Hecker, M.; Engelmann, S.; van Belkum, A. Distinctive patterns in the human antibody response to Staphylococcus aureus bacteremia in carriers and non-carriers. Proteomics 2011, 11, 3914-3927.
27. Fritz, S.A.; Tiemann, K.M.; Hogan, P.G.; Epplin, E.K.; Rodriguez, M.; Al-Zubeidi, D.N.; Bubeck Wardenburg, J.; Hunstad, D.A. A serologic correlate of protective immunity against community-onset Staphylococcus aureus infection. Clin. Infect. Dis. 2013, 56, 1554-1561.
28. Bubeck Wardenburg, J.; Bae, T.; Otto, M.; Deleo, F.R.; Schneewind, O. Poring over pores: Alpha-hemolysin and panton-valentine leukocidin in Staphylococcus aureus pneumonia. Nat. Med. 2007, 13, 1405-1406.
29. Frank, K.M.; Zhou, T.; Moreno-Vinasco, L.; Hollett, B.; Garcia, J.G.; Bubeck Wardenburg, J. Host response signature to Staphylococcus aureus alpha-hemolysin implicates pulmonary th17 response. Infect. Immun. 2012, 80, 3161-3169.
30. Kennedy, A.D.; Bubeck Wardenburg, J.; Gardner, D.J.; Long, D.; Whitney, A.R.; Braughton, K.R.; Schneewind, O.; DeLeo, F.R. Targeting of alpha-hemolysin by active or passive immunization decreases severity of USA300 skin infection in a mouse model. J. Infect. Dis. 2010, 202, 1050-1058.
31. Kebaier, C.; Chamberland, R.R.; Allen, I.C.; Gao, X.; Broglie, P.M.; Hall, J.D.; Jania, C.; Doerschuk, C.M.; Tilley, S.L.; Duncan, J.A. Staphylococcus aureus alpha-hemolysin mediates virulence in a murine model of severe pneumonia through activation of the nlrp3 inflammasome. J. Infect. Dis. 2012, 205, 807-817.
32. Kielian, T.; Cheung, A.; Hickey, W.F. Diminished virulence of an alpha-toxin mutant of Staphylococcus aureus in experimental brain abscesses. Infect. Immun. 2001, 69, 6902-6911.
33. O'Callaghan, R.J.; Callegan, M.C.; Moreau, J.M.; Green, L.C.; Foster, T.J.; Hartford, O.M.; Engel, L.S.; Hill, J.M. Specific roles of alpha-toxin and beta-toxin during Staphylococcus aureus corneal infection. Infect. Immun. 1997, 65, 1571-1578.
34. Arbuthnott, J.P. Staphylococcal Alpha-toxin. In Microbial Toxins; Montie, T.C., Kadis, S., Ajl, S.I., Eds.; Academic Press: New York, NY, USA, 1970; Volume III, pp. 189-236.
35. Wiseman, G.M. The hemolysins of Staphylococcus aureus. Bacteriol. Rev. 1975, 39, 317-344.
36. Gouaux, E. Alpha-hemolysin from Staphylococcus aureus: An archetype of beta-barrel, channel-forming toxins. J. Struct. Biol. 1998, 121, 110-122.
37. De Christmas, M.J. Recherches expérimentales sur la suppuration. Ann. Inst. Pasteur 1888, 2, 469.
38. Von Leber, T. Uber die entstehung der entzundung und die wirkung der entzundungserregenden schadlichkeiten. Fortschr. Med. 1888, 6, 460.
39. Breiger, L.; Fraenkel, C. Untersuchungen uber bacteriengifte. Berlin Klin. Wochschr. 1890, 27, 241.
40. Rodet, A.; Courmont, J. Produits du staphylocoque pyogène. Bull. Med. 1892, 23, 84.
41. Van de Velde, H. Mécanisme de la virulence du staphylocoque pyogène. Cellule 1894, 10, 401.
42. Neisser, M.; Wechsberg, F. Ueber das staphylotoxin. Z. Hyg. Infektionskrankh 1901, 36, 299.
43. Kraus, R.; Pribram, E. Ueber staphylokokkentoxin und dessen antitoxin. Wien. Klin. Wochschr. 1906, 17, 493.
44. Royal Commission of Inquiry into Fatalities at Bundaberg. Report of the Royal Commission of Inquiry into Fatalities at Bundaberg, Together with Appendices; Green, H.J., Ed.; Government Printer: Melbourne, Australia, 1928.
45. Elek, S.D. Staphylococcus Pyogenes; E. and S. Livingstone, Ltd.: Edinburgh, UK, 1959.
46. Glenny, A.T.; Stevens, M.F. Staphylococcus toxins and antitoxins. J. Pathol. Bacteriol. 1935, 40, 201-210.
47. Cooper, L.Z.; Madoff, M.A.; Weinstein, L. Heat stability and species range of purified staphylococcal alpha-toxin. J. Bacteriol. 1966, 91, 1686-1692.
48. Bernheimer, A.W.; Avigad, L.S.; Grushoff, P. Lytic effects of staphylococcal alpha-toxin and delta-hemolysin. J. Bacteriol. 1968, 96, 487-491.
49. Cooper, L.Z.; Madoff, M.A.; Weinstein, L. Hemolysis of rabbit erythrocytes by purified staphylococcal alpha-toxin. I. Kinetics of the lytic reaction. J. Bacteriol. 1964, 87, 127-135.
50. Kumar, S.; Lindorfer, R.K. The characterization of staphylococcal toxins. I. The electrophoretic migration of the alpha hemolytic, dermonecrotic, lethal, and leucocidal activities of crude toxin. J. Exp. Med. 1962, 115, 1095-1106.
51. Bernheimer, A.W.; Schwartz, L.L. Isolation and composition of staphylococcal alpha toxin. J. Gen. Microbiol. 1963, 30, 455-468.
52. Weissmann, G.; Sessa, G.; Bernheimer, A.W. Staphylococcal alpha-toxin: Effects on artificial lipid spherules. Science 1966, 154, 772-774.
53. Thelestam, M.; Mollby, R.; Wadstrom, T. Effects of staphylococcal alpha-, beta-, delta-, and gamma-hemolysins on human diploid fibroblasts and hela cells: Evaluation of a new quantitative as say for measuring cell damage. Infect. Immun. 1973, 8, 938-946.
54. Thelestam, M.; Mollby, R. Sensitive assay for detection of toxin-induced damage to the cytoplasmic membrane of human diploid fibroblasts. Infect. Immun. 1975, 12, 225-232.
55. Thelestam, M.; Mollby, R. Determination of toxin-induced leakage of different-size nucleotides through the plasma membrane of human diploid fibroblasts. Infect. Immun. 1975, 11, 640-648.
56. Fussle, R.; Bhakdi, S.; Sziegoleit, A.; Tranum-Jensen, J.; Kranz, T.; Wellensiek, H.J. On the mechanism of membrane damage by Staphylococcus aureus alpha-toxin. J. Cell Biol. 1981, 91, 83-94.
57. Freer, J.H.; Arbuthnott, J.P.; Bernheimer, A.W. Interaction of staphylococcal alpha-toxin with artificial and natural membranes. J. Bacteriol. 1968, 95, 1153-1168.
58. Kehoe, M.; Duncan, J.; Foster, T.; Fairweather, N.; Dougan, G. Cloning, expression, and mapping of the Staphylococcus aureus alpha-hemolysin determinant in Escherichia coli k-12. Infect. Immun. 1983, 41, 1105-1111.
59. Fairweather, N.; Kennedy, S.; Foster, T.J.; Kehoe, M.; Dougan, G. Expression of a cloned Staphylococcus aureus alpha-hemolysin determinant in Bacillus subtilis and Staphylococcus aureus. Infect. Immun. 1983, 41, 1112-1117.
60. Gray, G.S.; Kehoe, M. Primary sequence of the alpha-toxin gene from Staphylococcus aureus Wood 46. Infect. Immun. 1984, 46, 615-618.
61. Tweten, R.K.; Christianson, K.K.; Iandolo, J.J. Transport and processing of staphylococcal alpha-toxin. J. Bacteriol. 1983, 156, 524-528.
62. Tobkes, N.; Wallace, B.A.; Bayley, H. Secondary structure and assembly mechanism of an oligomeric channel protein. Biochemistry 1985, 24, 1915-1920.
63. Arbuthnott, J.P.; Freer, J.H.; Bernheimer, A.W. Physical states of staphylococcal alpha-toxin. J. Bacteriol. 1967, 94, 1170-1177.
64. Remsen, C.C.; Watson, S.W.; Bernheimer, A.W. Evidence for an ordered arrangement in erythrocyte membranes. Biochem. Biophys. Res. Commun. 1970, 40, 1297-1304.
65. Freer, J.H.; Arbuthnott, J.P.; Billcliffe, B. Effects of staphylococcal-toxin on the structure of erythrocyte membranes: A biochemical and freeze-etching study. J. Gen. Microbiol. 1973, 75, 321-332.
66. Arbuthnott, J.P.; Freer, J.H.; Billcliffe, B. Lipid-induced polymerization of staphylococcal-toxin. J. Gen. Microbiol. 1973, 75, 309-319.
67. Arbuthnott, J.P.; Freer, J.H.; McNiven, A.C. Physical properties of staphylococcal alpha-toxin and aspects of alpha-toxin membrane interactions. Contrib. Microbiol. Immunol. 1973, 1, 285-297.
68. Hugo, F.; Sinner, A.; Reichwein, J.; Bhakdi, S. Quantitation of monomeric and oligomeric forms of membrane-bound staphylococcal alpha-toxin by enzyme-linked immunosorbent assay with a neutralizing monoclonal antibody. Infect. Immun. 1987, 55, 2933-2939.
69. Reichwein, J.; Hugo, F.; Roth, M.; Sinner, A.; Bhakdi, S. Quantitative analysis of the binding and oligomerization of staphylococcal alpha-toxin in target erythrocyte membranes. Infect. Immun. 1987, 55, 2940-2944.
70. Bhakdi, S.; Fussle, R.; Tranum-Jensen, J. Staphylococcal alpha-toxin: Oligomerization of hydrophilic monomers to form amphiphilic hexamers induced through contact with deoxycholate detergent micelles. Proc. Natl. Acad. Sci. USA 1981, 78, 5475-5479.
71. Recsei, P.; Kreiswirth, B.; O'Reilly, M.; Schlievert, P.; Gruss, A.; Novick, R.P. Regulation of exoprotein gene expression in Staphylococcus aureus by agar. Mol. Gen. Genet. 1986, 202, 58-61.
72. Peng, H.L.; Novick, R.P.; Kreiswirth, B.; Kornblum, J.; Schlievert, P. Cloning, characterization, and sequencing of an accessory gene regulator (agr) in Staphylococcus aureus. J. Bacteriol. 1988, 170, 4365-4372.
73. Novick, R.P.; Ross, H.F.; Projan, S.J.; Kornblum, J.; Kreiswirth, B.; Moghazeh, S. Synthesis of staphylococcal virulence factors is controlled by a regulatory RNA molecule. EMBO J. 1993, 12, 3967-3975.
74. Lina, G.; Jarraud, S.; Ji, G.; Greenland, T.; Pedraza, A.; Etienne, J.; Novick, R.P.; Vandenesch, F. Transmembrane topology and histidine protein kinase activity of agrC, the agr signal receptor in Staphylococcus aureus. Mol. Microbiol. 1998, 28, 655-662.
75. Lyon, G.J.; Wright, J.S.; Muir, T.W.; Novick, R.P. Key determinants of receptor activation in the agr autoinducing peptides of Staphylococcus aureus. Biochemistry 2002, 41, 10095-10104.
76. Koenig, R.L.; Ray, J.L.; Maleki, S.J.; Smeltzer, M.S.; Hurlburt, B.K. Staphylococcus aureus agrA binding to the RNAIII-agr regulatory region. J. Bacteriol. 2004, 186, 7549-7555.
77. McNiven, A.C.; Arbuthnott, J.P. Cell-associated alpha-toxin from Staphylococcus aureus. J. Med. Microbiol. 1972, 5, 123-127.
78. Xiong, Y.Q.; Willard, J.; Yeaman, M.R.; Cheung, A.L.; Bayer, A.S. Regulation of Staphylococcus aureus alpha-toxin gene (hla) expression by agr, sarA, and sae in vitro and in experimental infective endocarditis. J. Infect. Dis. 2006, 194, 1267-1275.
79. Reyes, D.; Andrey, D.O.; Monod, A.; Kelley, W.L.; Zhang, G.; Cheung, A.L. Coordinated regulation by agrA, sarA, and sarR to control agr expression in Staphylococcus aureus. J. Bacteriol. 2011, 193, 6020-6031.
80. Cheung, A.L.; Chien, Y.T.; Bayer, A.S. Hyperproduction of alpha-hemolysin in a sigB mutant is associated with elevated sarA expression in Staphylococcus aureus. Infect. Immun. 1999, 67, 1331-1337.
81. Cheung, A.L.; Eberhardt, K.J.; Chung, E.; Yeaman, M.R.; Sullam, P.M.; Ramos, M.; Bayer, A.S. Diminished virulence of a sar-/agr-mutant of Staphylococcus aureus in the rabbit model of endocarditis. J. Clin. Invest. 1994, 94, 1815-1822.
82. Valeva, A.; Hellmann, N.; Walev, I.; Strand, D.; Plate, M.; Boukhallouk, F.; Brack, A.; Hanada, K.; Decker, H.; Bhakdi, S. Evidence that clustered phosphocholine head groups serve as sites for binding and assembly of an oligomeric protein pore. J. Biol. Chem. 2006, 281, 26014-26021.
83. Menestrina, G. Ionic channels formed by Staphylococcus aureus alpha-toxin: Voltage-dependent inhibition by divalent and trivalent cations. J. Membr. Biol. 1986, 90, 177-190.
84. Watanabe, M.; Tomita, T.; Yasuda, T. Membrane-damaging action of staphylococcal alpha-toxin on phospholipid-cholesterol liposomes. Biochim. Biophys. Acta 1987, 898, 257-265.
85. Belmonte, G.; Cescatti, L.; Ferrari, B.; Nicolussi, T.; Ropele, M.; Menestrina, G. Pore formation by Staphylococcus aureus alpha-toxin in lipid bilayers. Dependence upon temperature and toxin concentration. Eur. Biophys. J. 1987, 14, 349-358.
86. Ikigai, H.; Nakae, T. Assembly of the alpha-toxin-hexamer of Staphylococcus aureus in the liposome membrane. J. Biol. Chem. 1987, 262, 2156-2160.
87. Ikigai, H.; Nakae, T. Interaction of the alpha-toxin of Staphylococcus aureus with the liposome membrane. J. Biol. Chem. 1987, 262, 2150-2155.
88. Forti, S.; Menestrina, G. Staphylococcal alpha-toxin increases the permeability of lipid vesicles by cholesterol-and ph-dependent assembly of oligomeric channels. Eur. J. Biochem. 1989, 181, 767-773.
89. Schwiering, M.; Brack, A.; Stork, R.; Hellmann, N. Lipid and phase specificity of alpha-toxin from S. aureus. Biochim. Biophys. Acta 2013, 1828, 1962-1972.
90. Galdiero, S.; Gouaux, E. High resolution crystallographic studies of alpha-hemolysin-phospholipid complexes define heptamer-lipid head group interactions: Implication for understanding protein-lipid interactions. Protein Sci. 2004, 13, 1503-1511.
91. Tweten, R.K. Cholesterol-dependent cytolysins, a family of versatile pore-forming toxins. Infect. Immun. 2005, 73, 6199-6209.
92. Thay, B.; Wai, S.N.; Oscarsson, J. Staphylococcus aureus alpha-toxin-dependent induction of host cell death by membrane-derived vesicles. PLoS One 2013, 8, e54661.
93. Lee, E.Y.; Choi, D.Y.; Kim, D.K.; Kim, J.W.; Park, J.O.; Kim, S.; Kim, S.H.; Desiderio, D.M.; Kim, Y.K.; Kim, K.P. Gram-positive bacteria produce membrane vesicles: Proteomics-based characterization of Staphylococcus aureus-derived membrane vesicles. Proteomics 2009, 9, 5425-5436.
94. Wilke, G.A.; Bubeck Wardenburg, J. Role of a disintegrin and metalloprotease 10 in Staphylococcus aureus alpha-hemolysin-mediated cellular injury. Proc. Natl. Acad. Sci. USA 2010, 107, 13473-13478.
95. Gouaux, E.; Hobaugh, M.; Song, L. Alpha-hemolysin, gamma-hemolysin, and leukocidin from Staphylococcus aureus: Distant in sequence but similar in structure. Protein Sci. 1997, 6, 2631-2635.
96. Valeva, A.; Palmer, M.; Bhakdi, S. Staphylococcal α-toxin: Formation of the heptameric pore is partially cooperative and proceeds through multiple intermediate stages?. Biochemistry 1997, 36, 13298-13304.
97. Valeva, A.; Pongs, J.; Bhakdi, S.; Palmer, M. Staphylococcal alpha-toxin: The role of the n-terminus in formation of the heptameric pore-A fluorescence study. Biochim. Biophys. Acta 1997, 1325, 281-286.
98. Kawate, T.; Gouaux, E. Arresting and releasing staphylococcal α-hemolysin at intermediate stages of pore formation by engineered disulfide bonds. Protein Sci. 2003, 12, 997-1006.
99. Jursch, R.; Hildebrand, A.; Hobom, G.; Tranum-Jensen, J.; Ward, R.; Kehoe, M.; Bhakdi, S. Histidine residues near the N-terminus of staphylococcal alpha-toxin as reporters of regions that are critical for oligomerization and pore formation. Infect. Immun. 1994, 62, 2249-2256.
100. Menzies, B.E.; Kernodle, D.S. Site-directed mutagenesis of the alpha-toxin gene of Staphylococcus aureus: Role of histidines in toxin activity in vitro and in a murine model. Infect. Immun. 1994, 62, 1843-1847.
101. Walker, B.; Bayley, H. Key residues for membrane binding, oligomerization, and pore forming activity of staphylococcal alpha-hemolysin identified by cysteine scanning mutagenesis and targeted chemical modification. J. Biol. Chem. 1995, 270, 23065-23071.
102. Walker, B.; Bayley, H. Restoration of pore-forming activity in staphylococcal alpha-hemolysin by targeted covalent modification. Protein Eng. 1995, 8, 491-495.
103. Jayasinghe, L.; Miles, G.; Bayley, H. Role of the amino latch of staphylococcal alpha-hemolysin in pore formation: A co-operative interaction between the N-terminus and position 217. J. Biol. Chem. 2006, 281, 2195-2204.
104. Meesters, C.; Brack, A.; Hellmann, N.; Decker, H. Structural characterization of the alpha-hemolysin monomer from Staphylococcus aureus. Proteins 2009, 75, 118-126.
105. Foletti, D.; Strop, P.; Shaughnessy, L.; Hasa-Moreno, A.; Casas, M.G.; Russell, M.; Bee, C.; Wu, S.; Pham, A.; Zeng, Z. Mechanism of action and in vivo efficacy of a human-derived antibody against Staphylococcus aureus alpha-hemolysin. J. Mol. Biol. 2013, 425, 1641-1654.
106. Bhakdi, S.; Jursch, R.; Broker, M.; Ronneberger, H.; Hungerer, K.D. Functionally inactive S. aureus alpha-toxin containing a single amino acid substitution: Potential usefulness as a vaccine. Behring Inst. Mitteilungen 1994, 95, 80-84.
107. Ragle, B.E.; Bubeck Wardenburg, J. Anti-alpha-hemolysin monoclonal antibodies mediate protection against Staphylococcus aureus pneumonia. Infect. Immun. 2009, 77, 2712-2718.
108. Tkaczyk, C.; Hua, L.; Varkey, R.; Shi, Y.; Dettinger, L.; Woods, R.; Barnes, A.; MacGill, R.S.; Wilson, S.; Chowdhury, P. Identification of anti-alpha toxin monoclonal antibodies that reduce the severity of Staphylococcus aureus dermonecrosis and exhibit a correlation between affinity and potency. Clin. Vaccine Immunol. 2012, 19, 377-385.
109. Adhkari, R.P.; Ajao, A.O.; Aman, M.J.; Karauzum, H.; Sarwar, J.; Lydecker, A.D.; Johnson, J.K.; Nguyen, C.; Chen, W.H.; Roghmann, M.C. Lower antibody levels to Staphylococcus aureus exotoxins are associated with sepsis in hospitalized adults with invasive S. aureus infections. J. Infect. Dis. 2012, 206, 915-923.
110. Roundtree, P.M.; Beard, M.A. Further observations on infections with phage type 80 staphylococci in australia. Med. J. Aust. 1958, 2, 789-795.
111. Gillespie, W.A.; Alder, V.G. Control of an outbreak of staphylococcal infection in a hospital. Lancet 1957, 272, 632-634.
112. Hassall, J.E.; Rountree, P.M. Staphylococcal septicaemia. Lancet 1959, 1, 213-217.
113. DeLeo, F.R.; Kennedy, A.D.; Chen, L.; Bubeck Wardenburg, J.; Kobayashi, S.D.; Mathema, B.; Braughton, K.R.; Whitney, A.R.; Villaruz, A.E.; Martens, C.A. Molecular differentiation of historic phage-type 80/81 and contemporary epidemic Staphylococcus aureus. Proc. Natl. Acad. Sci. USA 2011, 108, 18091-18096.
114. Montgomery, C.P.; Boyle-Vavra, S.; Adem, P.V.; Lee, J.C.; Husain, A.N.; Clasen, J.; Daum, R.S. Comparison of virulence in community-associated methicillin-resistant Staphylococcus aureus pulsotypes usa300 and usa400 in a rat model of pneumonia. J. Infect. Dis. 2008, 198, 561-570.
115. Montgomery, C.P.; Boyle-Vavra, S.; Daum, R.S. Importance of the global regulators agr and saeRS in the pathogenesis of CA-MRSA USA300 infection. PLoS One 2010, 5, e15177.
116. Bubeck Wardenburg, J.; Schneewind, O. Vaccine protection against Staphylococcus aureus pneumonia. J. Exp. Med. 2008, 205, 287-294.
117. Barretti, P.; Montelli, A.C.; Batalha, J.E.; Caramori, J.C.; Cunha Mde, L. The role of virulence factors in the outcome of staphylococcal peritonitis in capd patients. BMC Infect. Dis. 2009, 9, 212.
118. Patel, A.H.; Nowlan, P.; Weavers, E.D.; Foster, T. Virulence of protein a-deficient and alpha-toxin-deficient mutants of Staphylococcus aureus isolated by allele replacement. Infect. Immun. 1987, 55, 3103-3110.
119. Menzies, B.E.; Kernodle, D.S. Passive immunization with antiserum to a nontoxic alpha-toxin mutant from Staphylococcus aureus is protective in a murine model. Infect. Immun. 1996, 64, 1839-1841.
120. O'Reilly, M.; de Azavedo, J.C.; Kennedy, S.; Foster, T.J. Inactivation of the alpha-haemolysin gene of Staphylococcus aureus 8325-4 by site-directed mutagenesis and studies on the expression of its haemolysins. Microbial. Pathog. 1986, 1, 125-138.
121. Rauch, S.; DeDent, A.C.; Kim, H.K.; Bubeck Wardenburg, J.; Missiakas, D.M.; Schneewind, O. Abscess formation and alpha-hemolysin induced toxicity in a mouse model of Staphylococcus aureus peritoneal infection. Infect. Immun. 2012, 80, 3721-3732.
122. Bayer, A.S.; Ramos, M.D.; Menzies, B.E.; Yeaman, M.R.; Shen, A.J.; Cheung, A.L. Hyperproduction of alpha-toxin by Staphylococcus aureus results in paradoxically reduced virulence in experimental endocarditis: A host defense role for platelet microbicidal proteins. Infect. Immun. 1997, 65, 4652-4660.
123. Bramley, A.J.; Patel, A.H.; O'Reilly, M.; Foster, R.; Foster, T.J. Roles of alpha-toxin and beta-toxin in virulence of Staphylococcus aureus for the mouse mammary gland. Infect. Immun. 1989, 57, 2489-2494.
124. Jonsson, P.; Lindberg, M.; Haraldsson, I.; Wadstrom, T. Virulence of staphylococcus aureus in a mouse mastitis model: Studies of alpha hemolysin, coagulase, and protein a as possible virulence determinants with protoplast fusion and gene cloning. Infect. Immun. 1985, 49, 765-769.
125. McGee, M.P.; Kreger, A.; Leake, E.S.; Harshman, S. Toxicity of staphylococcal alpha toxin for rabbit alveolar macrophages. Infect. Immun. 1983, 39, 439-444.
126. Yarovinsky, T.O.; Monick, M.M.; Husmann, M.; Hunninghake, G.W. Interferons increase cell resistance to staphylococcal alpha-toxin. Infect. Immun. 2008, 76, 571-577.
127. Hruz, P.; Zinkernagel, A.S.; Jenikova, G.; Botwin, G.J.; Hugot, J.P.; Karin, M.; Nizet, V.; Eckmann, L. Nod2 contributes to cutaneous defense against Staphylococcus aureus through alpha-toxin-dependent innate immune activation. Proc. Natl. Acad. Sci. USA 2009, 106, 12873-12878.
128. Lizak, M.; Yarovinsky, T.O. Phospholipid scramblase 1 mediates type I interferon-induced protection against staphylococcal alpha-toxin. Cell Host Microbe 2012, 11, 70-80.
129. Seals, D.F. The adams family of metalloproteases: Multidomain proteins with multiple functions. Genes Dev. 2003, 17, 7-30.
130. Edwards, D.; Handsley, M.; Pennington, C. The adam metalloproteinases. Mol. Aspects Med. 2008, 29, 258-289.
131. Nagano, O.; Murakami, D.; Hartmann, D.; de Strooper, B.; Saftig, P.; Iwatsubo, T.; Nakajima, M.; Shinohara, M.; Saya, H. Cell-matrix interaction via cd44 is independently regulated by different metalloproteinases activated in response to extracellular Ca(2+) influx and PKC activation. J. Cell Biol. 2004, 165, 893-902.
132. Allinson, T.M.; Parkin, E.T.; Turner, A.J.; Hooper, N.M. Adams family members as amyloid precursor protein alpha-secretases. J. Neurosci. Res. 2003, 74, 342-352.
133. Maretzky, T.; Reiss, K.; Ludwig, A.; Buchholz, J.; Scholz, F.; Proksch, E.; de Strooper, B.; Hartmann, D.; Saftig, P. Adam10 mediates E-cadherin shedding and regulates epithelial cell-cell adhesion, migration, and beta-catenin translocation. Proc. Natl. Acad. Sci. USA 2005, 102, 9182-9187.
134. Janes, P.W.; Saha, N.; Barton, W.A.; Kolev, M.V.; Wimmer-Kleikamp, S.H.; Nievergall, E.; Blobel, C.P.; Himanen, J.P.; Lackmann, M.; Nikolov, D.B. Adam meets eph: An adam substrate recognition module acts as a molecular switch for ephrin cleavage in trans. Cell 2005, 123, 291-304.
135. Gardiner, E.E.; Karunakaran, D.; Shen, Y.; Arthur, J.F.; Andrews, R.K.; Berndt, M.C. Controlled shedding of platelet glycoprotein (GP)VI and GPIb-IX-V by adam family metalloproteinases. J. Thromb. Haemost. 2007, 5, 1530-1537.
136. Schulte, A.; Schulz, B.; Andrzejewski, M.; Hundhausen, C.; Mletzko, S.; Achilles, J.; Reiss, K.; Paliga, K.; Weber, C.; Rosejohn, S. Sequential processing of the transmembrane chemokines cx3cl1 and cxcl16 by α-and γ-secretases. Biochem. Biophys. Res. Commun. 2007, 358, 233-240.
137. Schulz, B.; Pruessmeyer, J.; Maretzky, T.; Ludwig, A.; Blobel, C.P.; Saftig, P.; Reiss, K. Adam10 regulates endothelial permeability and t-cell transmigration by proteolysis of vascular endothelial cadherin. Circ. Res. 2008, 102, 1192-1201.
138. Gibb, D.R.; El Shikh, M.; Kang, D.J.; Rowe, W.J.; El Sayed, R.; Cichy, J.; Yagita, H.; Tew, J.G.; Dempsey, P.J.; Crawford, H.C. Adam10 is essential for notch2-dependent marginal zone b cell development and CD23 cleavage in vivo. J. Exp. Med. 2010, 207, 623-635.
139. Saftig, P.; Reiss, K. The "a disintegrin and metalloproteases" ADAM10 and ADAM17: Novel drug targets with therapeutic potential? Eur. J. Cell Biol. 2011, 90, 527-535.
140. Horiuchi, K.; Le Gall, S.; Schulte, M.; Yamaguchi, T.; Reiss, K.; Murphy, G.; Toyama, Y.; Hartmann, D.; Saftig, P.; Blobel, C.P. Substrate selectivity of epidermal growth factor-receptor ligand sheddases and their regulation by phorbol esters and calcium influx. Mol. Biol. Cell 2006, 18, 176-188.
141. Hartmann, D.; de Strooper, B.; Serneels, L.; Craessaerts, K.; Herreman, A.; Annaert, W.; Umans, L.; Lubke, T.; Lena Illert, A.; von Figura, K. The disintegrin/metalloprotease adam 10 is essential for notch signalling but not for alpha-secretase activity in fibroblasts. Hum. Mol. Genet. 2002, 11, 2615-2624.
142. Tian, L.; Wu, X.; Chi, C.; Han, M.; Xu, T.; Zhuang, Y. Adam10 is essential for proteolytic activation of notch during thymocyte development. Int. Immunol. 2008, 20, 1181-1187.
143. Weber, S.; Niessen, M.T.; Prox, J.; Lullmann-Rauch, R.; Schmitz, A.; Schwanbeck, R.; Blobel, C.P.; Jorissen, E.; de Strooper, B.; Niessen, C.M. The disintegrin/metalloproteinase ADAM10 is essential for epidermal integrity and notch-mediated signaling. Development 2011, 138, 495-505.
144. Glomski, K.; Monette, S.; Manova, K.; de Strooper, B.; Saftig, P.; Blobel, C.P. Deletion of ADAM10 in endothelial cells leads to defects in organ-specific vascular structures. Blood 2011, 118, 1163-1174.
145. Zhang, C.; Tian, L.; Chi, C.; Wu, X.; Yang, X.; Han, M.; Xu, T.; Zhuang, Y.; Deng, K. ADAM10 is essential for early embryonic cardiovascular development. Dev. Dyn. 2010, 239, 2594-2602.
146. Jorissen, E.; Prox, J.; Bernreuther, C.; Weber, S.; Schwanbeck, R.; Serneels, L.; Snellinx, A.; Craessaerts, K.; Thathiah, A.; Tesseur, I. The disintegrin/metalloproteinase ADAM10 is essential for the establishment of the brain cortex. J. Neurosci. 2010, 30, 4833-4844.
147. Yoda, M.; Kimura, T.; Tohmonda, T.; Uchikawa, S.; Koba, T.; Takito, J.; Morioka, H.; Matsumoto, M.; Link, D.C.; Chiba, K. Dual functions of cell-autonomous and non-cell-autonomous ADAM10 activity in granulopoiesis. Blood 2011, 118, 6939-6942.
148. Bhakdi, S.; Muhly, M.; Korom, S.; Hugo, F. Release of interleukin-1 beta associated with potent cytocidal action of staphylococcal alpha-toxin on human monocytes. Infect. Immun. 1989, 57, 3512-3519.
149. Suttorp, N.; Seeger, W.; Dewein, E.; Bhakdi, S.; Roka, L. Staphylococcal alpha-toxin-induced PGI2 production in endothelial cells: Role of calcium. Am. J. Physiol. 1985, 248, C127-C134.
150. Rose, F.; Dahlem, G.; Guthmann, B.; Grimminger, F.; Maus, U.; Hanze, J.; Duemmer, N.; Grandel, U.; Seeger, W.; Ghofrani, H.A. Mediator generation and signaling events in alveolar epithelial cells attacked by S. aureus alpha-toxin. Am. J. Physiol. Lung Cell. Mol. Physiol. 2002, 282, L207-L214.
151. Suttorp, N.; Fuhrmann, M.; Tannert-Otto, S.; Grimminger, F.; Bhadki, S. Pore-forming bacterial toxins potently induce release of nitric oxide in porcine endothelial cells. J. Exp. Med. 1993, 178, 337-341.
152. Seeger, W.; Birkemeyer, R.G.; Ermert, L.; Suttorp, N.; Bhakdi, S.; Duncker, H.R. Staphylococcal alpha-toxin-induced vascular leakage in isolated perfused rabbit lungs. Lab. Investig. J. Tech. Methods Pathol. 1990, 63, 341-349.
153. Buerke, M.; Sibelius, U.; Grandel, U.; Buerke, U.; Grimminger, F.; Seeger, W.; Meyer, J.; Darius, H. Staphylococcus aureus alpha toxin mediates polymorphonuclear leukocyte-induced vasocontraction and endothelial dysfunction. Shock 2002, 17, 30-35.
154. Suttorp, N.; Hessz, T.; Seeger, W.; Wilke, A.; Koob, R.; Lutz, F.; Drenckhahn, D. Bacterial exotoxins and endothelial permeability for water and albumin in vitro. Am. J. Physiol. 1988, 255, C368-C376.
155. Maretzky, T.; Scholz, F.; Koten, B.; Proksch, E.; Saftig, P.; Reiss, K. ADAM10-mediated e-cadherin release is regulated by proinflammatory cytokines and modulates keratinocyte cohesion in eczematous dermatitis. J. Invest. Dermatol. 2008, 128, 1737-1746.
156. Le Gall, S.M.; Bobe, P.; Reiss, K.; Horiuchi, K.; Niu, X.D.; Lundell, D.; Gibb, D.R.; Conrad, D.; Saftig, P.; Blobel, C.P. ADAMS 10 and 17 represent differentially regulated components of a general shedding machinery for membrane proteins such as transforming growth factor alpha, l-selectin, and tumor necrosis factor alpha. Mol. Biol. Cell 2009, 20, 1785-1794.
157. McElroy, M.C.; Harty, H.R.; Hosford, G.E.; Boylan, G.M.; Pittet, J.F.; Foster, T.J. Alpha-toxin damages the air-blood barrier of the lung in a rat model of Staphylococcus aureus-induced pneumonia. Infect. Immun. 1999, 67, 5541-5544.
158. Parker, D.; Prince, A. Immunopathogenesis of Staphylococcus aureus pulmonary infection. Semin. Immunopathol. 2012, 34, 281-297.
159. Miller, L.S.; Cho, J.S. Immunity against Staphylococcus aureus cutaneous infections. Nat. Rev. Immunol. 2011, 11, 505-518.
160. Bartlett, A.H.; Foster, T.J.; Hayashida, A.; Park, P.W. Alpha-toxin facilitates the generation of cxc chemokine gradients and stimulates neutrophil homing in Staphylococcus aureus pneumonia. J. Infect. Dis. 2008, 198, 1529-1535.
161. Suttorp, N.; Buerke, M.; Tannert-Otto, S. Stimulation of paf-synthesis in pulmonary artery endothelial cells by Staphylococcus aureus alpha-toxin. Thromb. Res. 1992, 67, 243-252.
162. Onogawa, T. Staphylococcal alpha-toxin synergistically enhances inflammation caused by bacterial components. FEMS Immunol. Med. Microbiol. 2002, 33, 15-21.
163. Fink, S.L.; Cookson, B.T. Apoptosis, pyroptosis, and necrosis: Mechanistic description of dead and dying eukaryotic cells. Infect. Immun. 2005, 73, 1907-1916.
164. Ragle, B.E.; Karginov, V.A.; Bubeck Wardenburg, J. Prevention and treatment of Staphylococcus aureus pneumonia with a beta-cyclodextrin derivative. Antimicrob. Agents Chemother. 2010, 54, 298-304.
165. Miller, L.S.; Pietras, E.M.; Uricchio, L.H.; Hirano, K.; Rao, S.; Lin, H.; O'Connell, R.M.; Iwakura, Y.; Cheung, A.L.; Cheng, G. Inflammasome-mediated production of il-1beta is required for neutrophil recruitment against Staphylococcus aureus in vivo. J. Immunol. 2007, 179, 6933-6942.
166. Niebuhr, M.; Mamerow, D.; Heratizadeh, A.; Satzger, I.; Werfel, T. Staphylococcal alpha-toxin induces a higher t cell proliferation and interleukin-31 in atopic dermatitis. Int. Arch. Allergy Immunol. 2011, 156, 412-415.
167. Cho, J.S.; Pietras, E.M.; Garcia, N.C.; Ramos, R.I.; Farzam, D.M.; Monroe, H.R.; Magorien, J.E.; Blauvelt, A.; Kolls, J.K.; Cheung, A.L. Il-17 is essential for host defense against cutaneous Staphylococcus aureus infection in mice. J. Clin. Invest. 2010, 120, 1762-1773.
168. Deshmukh, H.S.; Hamburger, J.B.; Ahn, S.H.; McCafferty, D.G.; Yang, S.R.; Fowler, V.G., Jr. Critical role of NOD2 in regulating the immune response to Staphylococcus aureus. Infect. Immun. 2009, 77, 1376-1382.
169. Van Beelen, A.J.; Zelinkova, Z.; Taanman-Kueter, E.W.; Muller, F.J.; Hommes, D.W.; Zaat, S.A.; Kapsenberg, M.L.; de Jong, E.C. Stimulation of the intracellular bacterial sensor NOD2 programs dendritic cells to promote interleukin-17 production in human memory T cells. Immunity 2007, 27, 660-669.
170. Valeva, A.; Walev, I.; Gerber, A.; Klein, J.; Palmer, M.; Bhakdi, S. Staphylococcal alpha-toxin: Repair of a calcium-impermeable pore in the target cell membrane. Mol. Microbiol. 2000, 36, 467-476.
171. Husmann, M.; Dersch, K.; Bobkiewicz, W.; Beckmann, E.; Veerachato, G.; Bhakdi, S. Differential role of p38 mitogen activated protein kinase for cellular recovery from attack by pore-forming S. aureus alpha-toxin or streptolysino. Biochem. Biophys. Res. Commun. 2006, 344, 1128-1134.
172. Husmann, M.; Beckmann, E.; Boller, K.; Kloft, N.; Tenzer, S.; Bobkiewicz, W.; Neukirch, C.; Bayley, H.; Bhakdi, S. Elimination of a bacterial pore-forming toxin by sequential endocytosis and exocytosis. FEBS Lett. 2009, 583, 337-344.
173. Bhakdi, S.; Mannhardt, U.; Muhly, M.; Hugo, F.; Ronneberger, H.; Hungerer, K.D. Human hyperimmune globulin protects against the cytotoxic action of staphylococcal alpha-toxin in vitro and in vivo. Infect. Immun. 1989, 57, 3214-3220.
174. Blomqvist, L.; Sjogren, A. Production and characterization of monoclonal antibodies against Staphylococcus aureus alpha-toxin. Toxicon 1988, 26, 265-273.
175. Spaulding, A.R.; Lin, Y.C.; Merriman, J.A.; Brosnahan, A.J.; Peterson, M.L.; Schlievert, P.M. Immunity to Staphylococcus aureus secreted proteins protects rabbits from serious illnesses. Vaccine 2012, 30, 5099-5109.
176. Adhikari, R.P.; Karauzum, H.; Sarwar, J.; Abaandou, L.; Mahmoudieh, M.; Boroun, A.R.; Vu, H.; Nguyen, T.; Devi, V.S.; Shulenin, S. Novel structurally designed vaccine for S. aureus alpha-hemolysin: Protection against bacteremia and pneumonia. PLoS One 2012, 7, e38567.
177. Pozzi, C.; Wilk, K.; Lee, J.C.; Gening, M.; Nifantiev, N.; Pier, G.B. Opsonic and protective properties of antibodies raised to conjugate vaccines targeting six Staphylococcus aureus antigens. PLoS One 2012, 7, e46648.