Staphylococcus aureus pore-forming toxins

Current Topics in Microbiology and Immunology

Volumn 409, Issue , 2017, Pages 121-144

  Reyes Robles, Tamara ^a   Torres, Victor J ^a  

^a NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADAM10 ENDOPEPTIDASE; CD11B ANTIGEN; CELL RECEPTOR; CHEMOKINE RECEPTOR; CHEMOKINE RECEPTOR CCR2; CHEMOKINE RECEPTOR CCR5; CHEMOKINE RECEPTOR CXCR1; CHEMOKINE RECEPTOR CXCR2; COMPLEMENT RECEPTOR; CYTOTOXIN; HEMOLYSIN; LEUKOCIDIN; MEMBRANE RECEPTOR; PANTON VALENTINE LEUKOCIDIN; PROTEIN C5AR; PROTEIN C5L2; PROTEIN DARC; PROTEIN HLGACB; PROTEIN LUKAB; PROTEIN LUKED; STAPHYLOCOCCUS ALPHA TOXIN; STAPHYLOCOCCUS TOXIN; UNCLASSIFIED DRUG; BACTERIAL TOXIN; CARRIER PROTEIN; VIRULENCE FACTOR;

BACTERIAL STRAIN; CYTOTOXICITY; HOST CELL; HUMAN; MOLECULAR MECHANICS; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN SECRETION; STAPHYLOCOCCUS AUREUS; STAPHYLOCOCCUS INFECTION; TOXIN ANALYSIS; TROPISM; SIGNAL TRANSDUCTION;

BACTERIAL TOXINS; CARRIER PROTEINS; SIGNAL TRANSDUCTION; STAPHYLOCOCCUS AUREUS; VIRULENCE FACTORS;

EID: 85041285784     PISSN: 0070217X     EISSN: 21969965     Source Type: Book Series    
DOI: 10.1007/82_2016_16     Document Type: Chapter

References (118)

1. Alonzo F III, Benson MA, Chen J, Novick RP, Shopsin B, Torres VJ (2012) Staphylococcus aureus leucocidin ED contributes to systemic infection by targeting neutrophils and promoting bacterial growth in vivo. Mol Microbiol 83:423–435
2. Alonzo F III, Kozhaya L, Rawlings SA, Reyes-Robles T, DuMont AL, Myszka DG, Landau NR, Unutmaz D, Torres VJ (2013) CCR5 is a receptor for Staphylococcus aureus leukotoxin ED. Nature 493:51–55
3. Alonzo F III, Torres VJ (2014) The bicomponent pore-forming leucocidins of Staphylococcus aureus. Microbiol Mol Biol Rev 78:199–230
4. Andreini C, Bertini I, Cavallaro G, Holliday GL, Thornton JM (2008) Metal ions in biological catalysis: from enzyme databases to general principles. J Biol Inorg Chem 13:1205–1218
5. Andrews SC, Robinson AK, Rodriguez-Quinones F (2003) Bacterial iron homeostasis. FEMS Microbiol Rev 27:215–237
6. Badarau A, Rouha H, Malafa S, Logan DT, Hakansson M, Stulik L, Dolezilkova I, Teubenbacher A, Gross K, Maierhofer B et al (2015) Structure-function analysis of heterodimer formation, oligomerization, and receptor binding of the Staphylococcus aureus bi-component toxin LukGH. J Biol Chem 290:142–156
7. Becker KW, Skaar EP (2014) Metal limitation and toxicity at the interface between host and pathogen. FEMS Microbiol Rev 38:1235–1249
8. Berube BJ, Bubeck Wardenburg J (2013) Staphylococcus aureus alpha-toxin: nearly a century of intrigue. Toxins (Basel) 5:1140–1166
9. Bhakdi S, Tranum-Jensen J (1991) Alpha-toxin of Staphylococcus aureus. Microbiol Rev 55:733–751
10. Bubeck Wardenburg J, Bae T, Otto M, Deleo FR, Schneewind O (2007a) Poring over pores: alpha-hemolysin and Panton-Valentine leukocidin in Staphylococcus aureus pneumonia. Nat Med 13:1405–1406
11. Bubeck Wardenburg J, Patel RJ, Schneewind O (2007b) Surface proteins and exotoxins are required for the pathogenesis of Staphylococcus aureus pneumonia. Infect Immun 75:1040– 1044
12. Bubeck Wardenburg J, Palazzolo-Ballance AM, Otto M, Schneewind O, DeLeo FR (2008) Panton-Valentine leukocidin is not a virulence determinant in murine models of community-associated methicillin-resistant Staphylococcus aureus disease. J Infect Dis 198:1166–1170
13. Burnet FM (1929) The exotoxins of Staphylococcus pyogenes aureus. J Pathol Bacteriol 32:717– 734
14. Burnet FM (1930) The production of staphylococcal toxin. J Pathol Bacteriol 33:1–16
15. Cassidy P, Harshman S (1976) Studies on the binding of staphylococcal 125I-labeled alpha-toxin to rabbit erythrocytes. Biochemistry 15:2348–2355
16. Colin DA, Mazurier I, Sire S, Finck-Barbancon V (1994) Interaction of the two components of leukocidin from Staphylococcus aureus with human polymorphonuclear leukocyte membranes: sequential binding and subsequent activation. Infect Immun 62:3184–3188
17. Cooney J, Kienle Z, Foster TJ, O’Toole PW (1993) The gamma-hemolysin locus of Staphylococcus aureus comprises three linked genes, two of which are identical to the genes for the F and S components of leukocidin. Infect Immun 61:768–771
18. Craven R, Gao X, Allen I, Gris D, Bubeck Wardenburg J, McElvania-Tekippe E, Ting J, Duncan J (2009) Staphylococcus aureus alpha-hemolysin activates the NLRP3-inflammasome in human and mouse monocytic cells. PloS One 4
19. Cremieux AC, Dumitrescu O, Lina G, Vallee C, Cote JF, Muffat-Joly M, Lilin T, Etienne J, Vandenesch F, Saleh-Mghir A (2009) Panton-valentine leukocidin enhances the severity of community-associated methicillin-resistant Staphylococcus aureus rabbit osteomyelitis. PLoS One 4:e7204
20. Dajcs JJ, Austin MS, Sloop GD, Moreau JM, Hume EB, Thompson HW, McAleese FM, Foster TJ, O’Callaghan RJ (2002a) Corneal pathogenesis of Staphylococcus aureus strain Newman. Invest Ophthalmol Vis Sci 43:1109–1115
21. Dajcs JJ, Thibodeaux BA, Girgis DO, O’Callaghan RJ (2002b) Corneal virulence of Staphylococcus aureus in an experimental model of keratitis. DNA Cell Biol 21:375–382
22. Dalla Serra M, Coraiola M, Viero G, Comai M, Potrich C, Ferreras M, Baba-Moussa L, Colin DA, Menestrina G, Bhakdi S et al (2005) Staphylococcus aureus bicomponent gamma-hemolysins, HlgA, HlgB, and HlgC, can form mixed pores containing all components. J Chem Inf Model 45:1539–1545
23. Denys J, Van de Velde H (1895) Sur la production d’une antileucocidine chez les lapin vaccinés contre le staphylocoque pyogène. La Cellule, 359–372
24. Diep BA, Chan L, Tattevin P, Kajikawa O, Martin TR, Basuino L, Mai TT, Marbach H, Braughton KR, Whitney AR et al (2010) Polymorphonuclear leukocytes mediate Staphylococcus aureus Panton-Valentine leukocidin-induced lung inflammation and injury. Proc Natl Acad Sci USA 107:5587–5592
25. DuMont AL, Nygaard TK, Watkins RL, Smith A, Kozhaya L, Kreiswirth BN, Shopsin B, Unutmaz D, Voyich JM, Torres VJ (2011) Characterization of a new cytotoxin that contributes to Staphylococcus aureus pathogenesis. Mol Microbiol 79:814–825
26. DuMont AL, Torres VJ (2014) Cell targeting by the Staphylococcus aureus pore-forming toxins: it’s not just about lipids. Trends Microbiol 22:21–27
27. DuMont AL, Yoong P, Day CJ, Alonzo F III, McDonald WH, Jennings MP, Torres VJ (2013a) Staphylococcus aureus LukAB cytotoxin kills human neutrophils by targeting the CD11b subunit of the integrin Mac-1. Proc Natl Acad Sci USA 110:10794–10799
28. DuMont AL, Yoong P, Surewaard BG, Benson MA, Nijland R, van Strijp JA, Torres VJ (2013b) Staphylococcus aureus elaborates leukocidin AB to mediate escape from within human neutrophils. Infect Immun 81:1830–1841
29. DuMont AL, Yoong P, Liu X, Day CJ, Chumbler NM, James DB, Alonzo F III, Bode NJ, Lacy DB, Jennings MP et al (2014) Identification of a crucial residue required for Staphylococcus aureus LukAB cytotoxicity and receptor recognition. Infect Immun 82:1268– 1276
30. Fackrell HB, Wiseman GM (1976) Properties of the gamma haemolysin of Staphylococcus aureus ‘Smith 5R’. J Gen Microbiol 92:11–24
31. Galy R, Bergeret F, Keller D, Mourey L, Prévost G, Maveyraud L (2012) Crystallization and preliminary crystallographic studies of both components of the staphylococcal LukE-LukD leukotoxin. Acta Cryst 68:663–667
32. Gauduchon V, Werner S, Prevost G, Monteil H, Colin DA (2001) Flow cytometric determination of Panton-Valentine leucocidin S component binding. Infect Immun 69:2390–2395
33. Gladstone GP, Van Heyningen WE (1957) Staphylococcal leucocidins. Br J Exp Pathol 38: 123–137
34. Glenny AT, Stevens MF (1935) Staphylococcus toxins and antitoxins. J Pathol Bacteriol 40:201– 210
35. Gouaux JE, Braha O, Hobaugh MR, Song L, Cheley S, Shustak C, Bayley H (1994) Subunit stoichiometry of staphylococcal alpha-hemolysin in crystals and on membranes: a heptameric transmembrane pore. Proc Natl Acad Sci USA 91:12828–12831
36. Graves SF, Kobayashi SD, Braughton KR, Whitney AR, Sturdevant DE, Rasmussen DL, Kirpotina LN, Quinn MT, DeLeo FR (2012) Sublytic concentrations of Staphylococcus aureus Panton-Valentine leukocidin alter human PMN gene expression and enhance bactericidal capacity. J Leukoc Biol 92:361–374
37. Gravet A, Colin DA, Keller D, Girardot R, Monteil H, Prevost G (1998) Characterization of a novel structural member, LukE-LukD, of the bi-component staphylococcal leucotoxins family. FEBS Lett 436:202–208
38. Gray GS, Kehoe M (1984) Primary sequence of the alpha-toxin gene from Staphylococcus aureus wood 46. Infect Immun 46:615–618
39. Green HJ (Ed) (1928) Royal commission of inquiry into fatalities at Bundaberg. Report of the Royal Commission of Inquity into Fatalities at Bundaberg, Together with Appendices. Government Printer; Melbourne, Australia
40. Guillet V, Keller D, Prevost G, Mourey L (2004a) Crystallization and preliminary crystallographic data of a leucotoxin S component from Staphylococcus aureus. Acta Crystallogr D Biol Crystallogr 60:310–313
41. Guillet V, Roblin P, Werner S, Coraiola M, Menestrina G, Monteil H, Prevost G, Mourey L (2004b) Crystal structure of leucotoxin S component: new insight into the Staphylococcal beta-barrel pore-forming toxins. J Biol Chem 279:41028–41037
42. Hildebrand A, Pohl M, Bhakdi S (1991) Staphylococcus aureus alpha-toxin. Dual mechanism of binding to target cells. J Biol Chem 266:17195–17200
43. Inoshima I, Inoshima N, Wilke GA, Powers ME, Frank KM, Wang Y, Bubeck Wardenburg J (2011) A Staphylococcus aureus pore-forming toxin subverts the activity of ADAM10 to cause lethal infection in mice. Nat Med 17:1310–1314
44. Jayasinghe L, Bayley H (2005) The leukocidin pore: evidence for an octamer with four LukF subunits and four LukS subunits alternating around a central axis. Protein Sci 14:2550–2561
45. Joubert O, Voegelin J, Guillet V, Tranier S, Werner S, Colin DA, Serra MD, Keller D, Monteil H, Mourey L et al (2007) Distinction between pore assembly by Staphylococcal alpha-Toxin versus Leukotoxins. J Biomed Biotechnol 2007:25935
46. Julianelle LA (1922) Studies of hemolytic staphylococci—Hemolytic activity—Biochemical reactions—Serologic reactions. J Infect Dis 31:256–284
47. Labandeira-Rey M, Couzon F, Boisset S, Brown EL, Bes M, Benito Y, Barbu EM, Vazquez V, Hook M, Etienne J et al (2007) Staphylococcus aureus panton-valentine leukocidin causes necrotizing pneumonia. Science 315:1130–1133
48. Lina G, Piemont Y, Godail-Gamot F, Bes M, Peter MO, Gauduchon V, Vandenesch F, Etienne J (1999) Involvement of Panton-Valentine leukocidin-producing Staphylococcus aureus in primary skin infections and pneumonia. Clin Infect Dis 29:1128–1132
49. Loffler B, Hussain M, Grundmeier M, Bruck M, Holzinger D, Varga G, Roth J, Kahl BC, Proctor RA, Peters G (2010) Staphylococcus aureus Panton-Valentine leukocidin is a very potent cytotoxic factor for human neutrophils. PLoS Pathog 6:e1000715
50. Loffler B, Niemann S, Ehrhardt C, Horn D, Lanckohr C, Lina G, Ludwig S, Peters G (2013) Pathogenesis of Staphylococcus aureus necrotizing pneumonia: the role of PVL and an influenza coinfection. Expert Rev Anti Infect Ther 11:1041–1051
51. Lubkin A, Torres VJ (2015) The ever-emerging complexity of alpha-toxin’s interaction with host cells. Proc Natl Acad Sci USA 112:14123–14124
52. Malachowa N, Kobayashi SD, Braughton KR, Whitney AR, Parnell MJ, Gardner DJ, Deleo FR (2012) Staphylococcus aureus Leukotoxin GH promotes inflammation. J Infect Dis 206:1185– 1193
53. Malachowa N, Kobayashi SD, Freedman B, Dorward DW, DeLeo FR (2013) Staphylococcus aureus leukotoxin GH promotes formation of neutrophil extracellular traps. J Immunol 191:6022–6029
54. Malachowa N, Whitney AR, Kobayashi SD, Sturdevant DE, Kennedy AD, Braughton KR, Shabb DW, Diep BA, Chambers HF, Otto M et al (2011) Global changes in Staphylococcus aureus gene expression in human blood. PLoS One 6:e18617
55. Maurer K, Reyes-Robles T, Alonzo F III, Durbin J, Torres VJ, Cadwell K (2015) Autophagy mediates tolerance to Staphylococcus aureus alpha-toxin. Cell Host Microbe 17:429–440
56. McCarthy AJ, Lindsay JA (2013) Staphylococcus aureus innate immune evasion is lineage-specific: a bioinfomatics study. Infect Genet Evol 19C:7–14
57. Melehani JH, James DB, DuMont AL, Torres VJ, Duncan JA (2015) Staphylococcus aureus Leukocidin A/B (LukAB) kills human monocytes via Host NLRP3 and ASC when extracellular, but not intracellular. PLoS Pathog 11:e1004970
58. Menestrina G, Dalla Serra M, Comai M, Coraiola M, Viero G, Werner S, Colin DA, Monteil H, Prevost G (2003) Ion channels and bacterial infection: the case of beta-barrel pore-forming protein toxins of Staphylococcus aureus. FEBS Lett 552:54–60
59. Miles G, Movileanu L, Bayley H (2002) Subunit composition of a bicomponent toxin: staphylococcal leukocidin forms an octameric transmembrane pore. Protein Sci 11:894–902
60. Monma N, Nguyen VT, Kaneko J, Higuchi H, Kamio Y (2004) Essential residues, W177 and R198, of LukF for phosphatidylcholine-binding and pore-formation by staphylococcal gamma-hemolysin on human erythrocyte membranes. J Biochem 136:427–431
61. Morinaga N, Kaihou Y, Noda M (2003) Purification, cloning and characterization of variant LukE-LukD with strong leukocidal activity of staphylococcal bi-component leukotoxin family. Microbiol Immunol 47:81–90
62. Mueller EA, Merriman JA, Schlievert PA (2015) Toxic shock syndrome toxin-1, not alpha toxin, mediated Bundaberg fatalities. Microbiology 161:2361–2368
63. Naimi TS, LeDell KH, Como-Sabetti K, Borchardt SM, Boxrud DJ, Etienne J, Johnson SK, Vandenesch F, Fridkin S, O’Boyle C et al (2003) Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection. JAMA 290:2976–2984
64. Neisser M, Wechsberg F (1901) Ueber das staphylotoxin. Med Microbiol Immunol 36:299–349
65. Nilsson IM, Hartford O, Foster T, Tarkowski A (1999) Alpha-toxin and gamma-toxin jointly promote Staphylococcus aureus virulence in murine septic arthritis. Infect Immun 67:1045– 1049
66. Noda M, Kato I, Hirayama T, Matsuda F (1980) Fixation and inactivation of staphylococcal leukocidin by phosphatidylcholine and ganglioside GM1 in rabbit polymorphonuclear leukocytes. Infect Immun 29:678–684
67. Novick RP, Subedi A (2007) The SaPIs: mobile pathogenicity islands of Staphylococcus. Chem Immunol Allergy 93:42–57
68. Nygaard TK, Pallister KB, Dumont AL, Dewald M, Watkins RL, Pallister EQ, Malone C, Griffith S, Horswill AR, Torres VJ et al (2012) Alpha-toxin induces programmed cell death of human T cells, B cells, and monocytes during USA300 infection. PLoS One 7:e36532
69. Olson R, Nariya H, Yokota K, Kamio Y, Gouaux E (1999) Crystal structure of staphylococcal LukF delineates conformational changes accompanying formation of a transmembrane channel. Nat Struct Biol 6:134–140
70. Ozawa T, Kaneko J, Kamio Y (1995) Essential binding of LukF of staphylococcal gamma-hemolysin followed by the binding of H gamma II for the hemolysis of human erythrocytes. Biosci Biotechnol Biochem 59:1181–1183
71. Panton PN, Valentine FCO (1932) Staphylococcal toxin. Lancet 1:506–508
72. Pedelacq JD, Maveyraud L, Prevost G, Baba-Moussa L, Gonzalez A, Courcelle E, Shepard W, Monteil H, Samama JP, Mourey L (1999) The structure of a Staphylococcus aureus leucocidin component (LukF-PV) reveals the fold of the water-soluble species of a family of transmembrane pore-forming toxins. Structure 7:277–287
73. Perret M, Badiou C, Lina G, Burbaud S, Benito Y, Bes M, Cottin V, Couzon F, Juruj C, Dauwalder O et al (2012) Cross-talk between S. aureus leukocidins-intoxicated macrophages and lung epithelial cells triggers chemokine secretion in an inflammasome-dependent manner. Cell Microbiol 14:1019–1036
74. Popov LM, Marceau CD, Starkl PM, Lumb JH, Shah J, Guerrera D, Cooper RL, Merakou C, Bouley DM, Meng W et al (2015) The adherens junctions control susceptibility to Staphylococcus aureus alpha-toxin. Proc Natl Acad Sci USA 112:14337–14342
75. Potrich C, Bastiani H, Colin DA, Huck S, Prevost G, Dalla Serra M (2009) The influence of membrane lipids in Staphylococcus aureus gamma-hemolysins pore formation. J Membr Biol 227:13–24
76. Powers ME, Becker RE, Sailer A, Turner JR, Bubeck Wardenburg J (2015) Synergistic action of Staphylococcus aureus alpha-toxin on platelets and myeloid lineage cells contributes to lethal sepsis. Cell Host Microbe 17:775–787
77. Powers ME, Kim HK, Wang Y, Bubeck Wardenburg J (2012) ADAM10 mediates vascular injury induced by Staphylococcus aureus alpha-hemolysin. J Infect Dis 206:352–356
78. Prevost G, Mourey L, Colin DA, Menestrina G (2001) Staphylococcal pore-forming toxins. Curr Top Microbiol Immunol 257:53–83
79. Reyes-Robles T, Alonzo F III, Kozhaya L, Lacy DB, Unutmaz D, Torres VJ (2013) Staphylococcus aureus leukotoxin ED targets the chemokine receptors CXCR1 and CXCR2 to kill leukocytes and promote infection. Cell Host Microbe 14:453–459
80. Rouha H, Badarau A, Visram ZC, Battles MB, Prinz B, Magyarics Z, Nagy G, Mirkina I, Stulik L, Zerbs M et al (2015) Five birds, one stone: neutralization of alpha-hemolysin and 4 bi-component leukocidins of Staphylococcus aureus with a single human monoclonal antibody. MAbs 7:243–254
81. Schaible UE, Kaufmann SH (2004) Iron and microbial infection. Nat Rev Microbiol 2:946–953
82. Scherr TD, Hanke ML, Huang O, James DB, Horswill AR, Bayles KW, Fey PD, Torres VJ, Kielian T (2015) Staphylococcus aureus biofilms induce macrophage dysfunction through leukocidin AB and alpha-toxin. MBio 6:
83. Schwiering M, Brack A, Stork R, Hellmann N (2013) Lipid and phase specificity of alpha-toxin from S. aureus. Biochim Biophys Acta 1828:1962–1972
84. Siqueira JA, Speeg-Schatz C, Freitas FI, Sahel J, Monteil H, Prevost G (1997) Channel-forming leucotoxins from Staphylococcus aureus cause severe inflammatory reactions in a rabbit eye model. J Med Microbiol 46:486–494
85. Skaar EP, Raffatellu M (2015) Metals in infectious diseases and nutritional immunity. Metallomics 7:926–928
86. Skaar EP, Schneewind O (2004) Iron-regulated surface determinants (Isd) of Staphylococcus aureus: stealing iron from heme. Microbes Infect 6:390–397
87. Song L, Hobaugh MR, Shustak C, Cheley S, Bayley H, Gouaux JE (1996) Structure of staphylococcal alpha-hemolysin, a heptameric transmembrane pore. Science 274:1859–1866
88. Spaan AN, Henry T, van Rooijen WJ, Perret M, Badiou C, Aerts PC, Kemmink J, de Haas CJ, van Kessel KP, Vandenesch F et al (2013) The staphylococcal toxin Panton-Valentine Leukocidin targets human C5a receptors. Cell Host Microbe 13:584–594
89. Spaan AN, Reyes-Robles T, Badiou C, Cochet S, Yoong P, Day CJ, de Haas CJC, Boguslawski K, van Kessel KPM, Vandenesh F et al (2015a). Staphylococcus aureus targets the Duffy antigen receptor for chemokines (DARC) to lyse erythrocytes. Cell Host Microbe (in press)
90. Spaan AN, Schiepers A, de Haas CJ, van Hooijdonk DD, Badiou C, Contamin H, Vandenesch F, Lina G, Gerard NP, Gerard C et al. (2015b) Differential interaction of the staphylococcal toxins panton-valentine leukocidin and gamma-hemolysin CB with human C5a Receptors. J Immunol
91. Spaan AN, Vrieling M, Wallet P, Badiou C, Reyes-Robles T, Ohneck EA, Benito Y, de Haas CJ, Day CJ, Jennings MP et al (2014) The staphylococcal toxins gamma-haemolysin AB and CB differentially target phagocytes by employing specific chemokine receptors. Nat Commun 5:5438
92. Sugawara T, Yamashita D, Kato K, Peng Z, Ueda J, Kaneko J, Kamio Y, Tanaka Y, Yao M (2015) Structural basis for pore-forming mechanism of staphylococcal alpha-hemolysin. Toxicon 108:226–231
93. Supersac G, Piemont Y, Kubina M, Prevost G, Foster TJ (1998) Assessment of the role of gamma-toxin in experimental endophthalmitis using a hlg-deficient mutant of Staphylococcus aureus. Microb Pathog 24:241–251
94. Szmigielski S, Jeljaszewicz J, Kobus M, Luczak M, Ludwicka A, Mollby R, Wadstrom T (1976) Cytotoxic effects of staphylococcal alpha-hemolysins, beta-hemolysins and gamma-hemolysins. Zbl Bakt-Int J Med M 691–705
95. Thomsen IP, Dumont AL, James DB, Yoong P, Saville BR, Soper N, Torres VJ, Creech CB (2014) Children with invasive Staphylococcus aureus disease exhibit a potently neutralizing antibody response to the cytotoxin LukAB. Infect Immun 82:1234–1242
96. Tomita N, Abe K, Kamio Y, Ohta M (2011) Cluster-forming property correlated with hemolytic activity by staphylococcal gamma-hemolysin transmembrane pores. FEBS Lett 585:3452– 3456
97. Tomita T, Watanabe M, Yarita Y (1993) Assembly and channel-forming activity of a naturally-occurring nicked molecule of Staphylococcus aureus alpha-toxin. Biochim Biophys Acta 1145:51–57
98. Valeva A, Hellmann N, Walev I, Strand D, Plate M, Boukhallouk F, Brack A, Hanada K, Decker H, Bhakdi S (2006) Evidence that clustered phosphocholine head groups serve as sites for binding and assembly of an oligomeric protein pore. J Biol Chem 281:26014–26021
99. Van de Velde H (1894) Etude sur le mécanisme de la virulence du staphylocoque pyogène. La Cellule, 403–460
100. Vandenesch F, Couzon F, Boisset S, Benito Y, Brown EL, Lina G, Etienne J, Bowden MG (2010) The Panton-Valentine leukocidin is a virulence factor in a murine model of necrotizing pneumonia. J Infect Dis 201, 967–969 (author reply 969–970)
101. Vandenesch F, Lina G, Henry T (2012) Staphylococcus aureus hemolysins, bi-component leukocidins, and cytolytic peptides: a redundant arsenal of membrane-damaging virulence factors? Front Cell Infect Microbiol 2:12
102. Vandenesch F, Naimi T, Enright MC, Lina G, Nimmo GR, Heffernan H, Liassine N, Bes M, Greenland T, Reverdy ME et al (2003) Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: worldwide emergence. Emerg Infect Dis 9:978–984
103. Ventura CL, Malachowa N, Hammer CH, Nardone GA, Robinson MA, Kobayashi SD, DeLeo FR (2010) Identification of a novel Staphylococcus aureus two-component leukotoxin using cell surface proteomics. PLoS One 5:e11634
104. Walker B, Krishnasastry M, Zorn L, Bayley H (1992) Assembly of the oligomeric membrane pore formed by Staphylococcal alpha-hemolysin examined by truncation mutagenesis. J Biol Chem 267:21782–21786
105. Watanabe M, Tomita T, Yasuda T (1987) Membrane-damaging action of staphylococcal alpha-toxin on phospholipid-cholesterol liposomes. Biochim Biophys Acta 898:257–265
106. Weinberg ED (1975) Nutritional immunity. Host’s attempt to withold iron from microbial invaders. JAMA 231:39–41
107. Weld JT, Gunther A (1931) Differentiation between certain toxic properties of filtrates of hemolytic Staphylococcus aureus. J Exp Med 54:315–322
108. Wilke GA, Bubeck Wardenburg J (2010) Role of a disintegrin and metalloprotease 10 in Staphylococcus aureus alpha-hemolysin-mediated cellular injury. Proc Natl Acad Sci USA 107:13473–13478
109. Woodin AM (1960) Purification of the two components of leucocidin from Staphylococcus aureus. Biochem J 75:158–165
110. Wright J (1936) Staphylococcal leucocidin (Neisser-Wechsberg type) and antileucocidin. Lancet 1:1002–1004
111. Yamashita D, Sugawara T, Takeshita M, Kaneko J, Kamio Y, Tanaka I, Tanaka Y, Yao M (2014) Molecular basis of transmembrane beta-barrel formation of staphylococcal pore-forming toxins. Nat Commun 5:4897
112. Yamashita K, Kawai Y, Tanaka Y, Hirano N, Kaneko J, Tomita N, Ohta M, Kamio Y, Yao M, Tanaka I (2011) Crystal structure of the octameric pore of staphylococcal gamma-hemolysin reveals the beta-barrel pore formation mechanism by two components. Proc Natl Acad Sci USA 108:17314–17319
113. Yanai M, Rocha MA, Matolek AZ, Chintalacharuvu A, Taira Y, Chintalacharuvu K, Beenhouwer DO (2014) Separately or combined, LukG/LukH is functionally unique compared to other staphylococcal bicomponent leukotoxins. PLoS One 9:e89308
114. Yokota K, Kamio Y (2000) Tyrosine72 residue at the bottom of rim domain in LukF crucial for the sequential binding of the staphylococcal gamma-hemolysin to human erythrocytes. Biosci Biotechnol Biochem 64:2744–2747
115. Yoong P, Pier GB (2012) Immune-activating properties of Panton-Valentine leukocidin improve the outcome in a model of methicillin-resistant Staphylococcus aureus pneumonia. Infect Immun 80:2894–2904
116. Yoong P, Torres VJ (2013) The effects of Staphylococcus aureus leukotoxins on the host: cell lysis and beyond. Curr Opin Microbiol 16:63–69
117. Yoong P, Torres VJ (2015) Counter inhibition between leukotoxins attenuates Staphylococcus aureus virulence. Nat Commun (in press)
118. Zivkovic A, Sharif O, Stich K, Doninger B, Biaggio M, Colinge J, Bilban M, Mesteri I, Hazemi P, Lemmens-Gruber R et al (2011) TLR 2 and CD14 mediate innate immunity and lung inflammation to staphylococcal Panton-Valentine leukocidin in vivo. J Immunol 186:1608– 1617