Skip to main content
SpringerLink
Log in

Structure and Function of the Two-Component Cytotoxins of Staphylococcus aureus – Learnings for Designing Novel Therapeutics

  • Chapter
  • First Online:
Protein Reviews

Part of the book series: Advances in Experimental Medicine and Biology ((PROTRE,volume 966))

Abstract

Staphylococcus aureus can produce up to five different bi-component cytotoxins: two gamma-hemolysins HlgAB and HlgCB, and leukocidins SF-PV (Panton Valentine leukocidin), ED (LukED) and GH (LukGH, also called LukAB). Their major function in S. aureus pathogenesis is to evade innate immunity by attacking phagocytic cells and to support bacterial growth by lysing red blood cells. The five cytotoxins display different levels of amino acid sequence conservation (30–82%), but all form a remarkably similar beta-barrel type pore structure (greatly resembling the mono-component toxin alpha-hemolysin) that inserts into the target cell membrane leading to necrotic cell death. This review provides an overview of the culmination of decades of research on the structure of these toxins, their unique sequence and structural features that helps to explain the observed functional differences, such as toxin potency towards different cell types and species, receptor specificity and formation of functional non-cognate toxin pairs. The vast knowledge accumulated in this field supports novel approaches and the design of therapeutics targeting these cytotoxins to tame virulence and fight S. aureus infections.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

C5aR:

C5a receptor

C5L2:

C5a-like receptor 2

CCR2 and CCR5:

C-C chemokine receptors type 2 and 5, respectively

CXCR1 and CXCR2:

CXC chemokine receptors 1 and 2, respectively

DARC:

Duffy antigen receptor

Hla:

alpha-hemolysin

HlgAB and CB:

gamma-hemolysins AB and CB

LukED and LukGH:

leukocidins ED and GH

LukSF-PV:

Panton-Valentine leukocidin

mAb:

monoclonal antibody

MES:

2-(N-morpholino)ethanesulfonic acid

MPD:

2-methylpentane-2,4-diol

PC:

phosphocholine

PFTs:

pore forming toxins

PMNs:

polymorphonuclear cell

RBCs:

red blood cells

Cα rmsd:

root mean square deviation of the α-carbons

ST:

sequence type

References

  • Adhikari RP, Kort T, Shulenin S, Kanipakala T, Ganjbaksh N, Roghmann MC, Holtsberg FW, Aman MJ (2015) Antibodies to S. aureus LukS-PV attenuated subunit vaccine neutralize a broad spectrum of canonical and non-canonical bicomponent leukotoxin pairs. PLoS One 10:e0137874

    Article  PubMed  PubMed Central  Google Scholar 

  • Alonzo F 3rd, Torres VJ (2014) The bicomponent pore-forming leucocidins of Staphylococcus aureus. Microbiol Mol Biol Rev 78:199–230

    Google Scholar 

  • Alonzo F 3rd, 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

    Article  PubMed  Google Scholar 

  • Badarau A, Rouha H, Malafa S, Logan DT, Håkansson M, Stulik L, Dolezilkova I, Teubenbacher A, Gross K, Maierhofer B, Weber S, Jägerhofer M, Hoffman D, Nagy E (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

    Article  CAS  PubMed  Google Scholar 

  • Badarau A, Rouha H, Malafa S, Battles MB, Walker L, Nielson N, Dolezilkova I, Teubenbacher A, Banerjee S, Maierhofer B, Weber S, Stulik L, Logan DT, Welin M, Mirkina I, Pleban C, Zauner G, Gross K, Jägerhofer M, Magyarics Z, Nagy E (2016) Context matters: the importance of dimerization-induced conformation of the LukGH leukocidin of Staphylococcus aureus for the generation of neutralizing antibodies. MAbs 8:1347–1360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berube BJ, Bubeck Wardenburg J (2013) Staphylococcus aureus α-toxin: nearly a century of intrigue. Toxins (Basel) 5:1140–1166

    Article  Google Scholar 

  • Dal Peraro M, van der Goot FG (2016) Pore-forming toxins: ancient, but never really out of fashion. Nat Rev Microbiol 14:77–92

    Article  PubMed  Google Scholar 

  • Dalla Serra M, Coraiola M, Viero G, Comai M, Potrich C, Ferreras M, Baba-Moussa L, Colin DA, Menestrina G, Bhakdi S, Prévost G (2005) Staphylococcus aureus bicomponent gamma-hemolysins, HlgA, HlgB, and HlgC, can form mixed pores containing all components. J Chem Inf Model 45:1539–1545

    Article  CAS  PubMed  Google Scholar 

  • Diep BA, Chan L, Tattevin P, Kajikawa O, Martin TR, Basuino L, Mai TT, Marbach H, Braughton KR, Whitney AR, Gardner DJ, Fan X, Tseng CW, Liu GY, Badiou C, Etienne J, Lina G, Matthay MA, DeLeo FR, Chambers HF (2010) Polymorphonuclear leukocytes mediate Staphylococcus aureus Panton-Valentine leukocidin-induced lung inflammation and injury. Proc Natl Acad Sci U S A 107:5587–5592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Diep BA, Le VTM, Visram ZC, Rouha H, Stulik L, Dip EC, Nagy G, Nagy E (2016) Improved protection in a rabbit model of CA-MRSA necrotizing pneumonia upon neutralization of leukocidins in addition to alpha-hemolysin. Antimicrob Agents Chemother 60:6333–6340

    Article  PubMed  PubMed Central  Google Scholar 

  • Dong J, Qiu J, Zhang Y, Lu C, Dai X, Wang J, Li H, Wang X, Tan W, Luo M, Niu X, Deng X (2013) Oroxylin A Inhibits hemolysis via hindering the self-assembly of α-hemolysin heptameric transmembrane pore. In: Livesay DR (ed) PLoS Comput Biol 9:e1002869

    Google Scholar 

  • Dryla A, Prustomersky S, Gelbmann D, Hanner M, Bettinger E, Kocsis B, Kustos T, Henics T, Meinke A, Nagy E (2005) Comparison of antibody repertoires against Staphylococcus aureus in healthy individuals and in acutely infected patients. Clin Diagn Lab Immunol 12:387–398

    CAS  PubMed  PubMed Central  Google Scholar 

  • DuMont AL, Yoong P, Day CJ, Alonzo F 3rd, McDonald WH, Jennings MP, Torres VJ (2013) Staphylococcus aureus LukAB cytotoxin kills human neutrophils by targeting the CD11b subunit of the integrin Mac-1. Proc Natl Acad Sci U S A 110:10794–10799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • DuMont AL, Yoong P, Liu X, Day CJ, Chumbler NM, James DBA, Alonzo F, Bode NJ, Lacy DB, Jennings MP, Torres VJ (2014) Identification of a crucial residue required for Staphylococcus aureus LukAB cytotoxicity and receptor recognition. Infect Immun 82:1268–1276

    Article  PubMed  PubMed Central  Google Scholar 

  • Fiaschi L, Di Paolo B, Scarselli M, Pozzi C, Tomaszewski K, Galletti B, Nardi-Dei V, Arcidiacono L, Mishra RP, Mori E, Pallaoro M, Falugi F, Torre A, Fontana MR, Soriani M, Bubeck Wardenburg J, Grandi G, Rappuoli R, Ferlenghi I, Bagnoli F (2016) Auto-assembling detoxified Staphylococcus aureus alpha-hemolysin mimicking the wild-type cytolytic toxin. In: Burns DL (ed) Clin Vaccine Immunol 23:442–450

    Google Scholar 

  • Foletti D, Strop P, Shaughnessy L, Hasa-Moreno A, Casas MG, Russell M, Bee C, Wu S, Pham A, Zeng Z, Pons J, Rajpal A, Shelton D (2013) Mechanism of action and in vivo efficacy of a human-derived antibody against Staphylococcus aureus α-hemolysin. J Mol Biol 425:1641–1654

    Article  CAS  PubMed  Google Scholar 

  • Gillet Y, Issartel B, Vanhems P, Fournet JC, Lina G, Bes M, Vandenesch F, Piémont Y, Brousse N, Floret D, Etienne J (2002) Association between Staphylococcus aureus strains carrying gene for Panton-Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients. Lancet 359:753–759

    Article  CAS  PubMed  Google Scholar 

  • Gravet A, Colin DA, Keller D, Giradot R, Monteil H, Prèvost G (1998) Characterization of a novel structural member, LukE-LukD, of the bi-component staphylococcal leucotoxins family. FEBS Lett 436:202–208

    Article  CAS  PubMed  Google Scholar 

  • Guillet V, Roblin P, Werner S, Coraiola M, Menestrina G, Monteil H, Prévost G, Mourey L (2004) Crystal structure of leucotoxin S component: new insight into the Staphylococcal beta-barrel pore-forming toxins. J Biol Chem 279:41028–41037

    Article  CAS  PubMed  Google Scholar 

  • Hua L, Hilliard JJ, Shi Y, Tkaczyk C, Cheng LI, Yu X, Datta V, Ren S, Feng H, Zinsou R, Keller A, O’Day T, Du Q, Cheng L, Damschroder M, Robbie G, Suzich J, Stover CK, Sellman BR (2014) Assessment of an anti-alpha-toxin monoclonal antibody for prevention and treatment of Staphylococcus aureus-induced pneumonia. Antimicrob Agents Chemother 58:1108–1117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Joubert O, Viero G, Keller D, Martinez E, Colin DA, Monteil H, Mourey L, Dalla Serra M, Prévost G (2006) Engineered covalent leucotoxin heterodimers form functional pores: insights into S–F interactions. Biochem J 396:381–389

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaneko J, Kamio Y (2004) Bacterial two-component and hetero-heptameric pore-forming cytolytic toxins: structures, pore-forming mechanism, and organization of the genes. Biosci Biotechnol Biochem 68:981–1003

    Article  CAS  PubMed  Google Scholar 

  • Karauzum H, Adhikari RP, Sarwar J, Devi VS, Abaandou L, Haudenschild C, Mahmoudieh M, Boroun AR, Vu H, Nguyen T, Warfield KL, Shulenin S, Aman MJ (2013) Structurally designed attenuated subunit vaccines for S. aureus LukS-PV and LukF-PV confer protection in a mouse bacteremia model. PLoS One 8:e65384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Katsumi H, Tomita T, Kaneko J, Kamio Y (1999) Vitronectin and its fragments purified as serum inhibitors of Staphylococcus aureus gamma-hemolysin and leukocidin, and their specific binding to the hlg2 and the LukS components of the toxins. FEBS Lett 460:451–456

    Article  CAS  PubMed  Google Scholar 

  • Kuehnert MJ, Kruszon-Moran D, Hill HA, McQuillan G, McAllister SK, Fosheim G, McDougal LK, Chaitram J, Jensen B, Fridkin SK, Killgore G, Tenover FC (2006) Prevalence of Staphylococcus aureus nasal colonization in the United States, 2001–2002. J Infect Dis 193:172–179

    Article  CAS  PubMed  Google Scholar 

  • Kuroda M, Ohta T, Uchiyama I, Baba T, Yuzawa H, Kobayashi I, Cui L, Oguchi A, Aoki K, Nagai Y, Lian J, Ito T, Kanamori M, Matsumaru H, Maruyama A, Murakami H, Hosoyama A, Mizutani-Ui Y, Takahashi NK, Sawano T, Inoue R, Kaito C, Sekimizu K, Hirakawa H, Kuhara S, Goto S, Yabuzaki J, Kanehisa M, Yamashita A, Oshima K, Furuya K, Yoshino C, Shiba T, Hattori M, Ogasawara N, Hayashi H, Hiramatsu K (2001) Whole genome sequencing of meticillin-resistant Staphylococcus aureus. Lancet 357:1225–1240

    Article  CAS  PubMed  Google Scholar 

  • Laventie BJ, Guérin F, Mourey L, Tawk MY, Jover E, Maveyraud L, Prévost G (2014) Residues essential for Panton-Valentine leukocidin S component binding to its cell receptor suggest both plasticity and adaptability in its interaction surface. In: Diep BA (ed) PLoS ONE 9:e92094

    Google Scholar 

  • Lewis M, Weaver CD, McClain MS (2010) Identification of small molecule inhibitors of Clostridium perfringens ε-toxin cytotoxicity using a cell-based high-throughput screen. Toxins (Basel) 2:1825–1847

    Article  CAS  Google Scholar 

  • Li H, Zhao X, Wang J, Dong Y, Meng S, Li R, Niu X, Deng X (2015) β-sitosterol interacts with pneumolysin to prevent Streptococcus pneumoniae infection. Sci Rep 5:17668

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lina G, Piémont 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

    Article  CAS  PubMed  Google Scholar 

  • Löffler B, Hussain M, Grundmeier M, Brück 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. In: Cheung A (ed) PLoS Pathog 6:e1000715

    Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Menestrina G (1986) Ionic channels formed by Staphylococcus aureus alpha-toxin: voltage-dependent inhibition by divalent and trivalent cations. J Membr Biol 90:177–190

    Article  CAS  PubMed  Google Scholar 

  • Meyer F, Girardot R, Piemont Y, Prevost G, Colin DA (2009) Analysis of the specificity of Panton-Valentine leucocidin and gamma-hemolysin F component binding. Infect Immun 77:266–273

    Article  CAS  PubMed  Google Scholar 

  • 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 -hemolysin on human erythrocyte membranes. J Biochem 136:427–431

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Nagy E, Badarau A, Rouha H, Nagy G, Mirkina I, Magyarics Z, Visram Z, Battles MB, Prinz BD, Jain TS (2013) Cross-reactive Staphylococcus aureus antibody. WO2013156534 A1. 24 Oct 2013

    Google Scholar 

  • Nguyen VT, Kamio Y, Higuchi H (2003) Single-molecule imaging of cooperative assembly of γ-hemolysin on erythrocyte membranes. EMBO J 22:4968–4979

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nocadello S, Minasov G, Shuvalova L, Dubrovska I, Sabini E, Bagnoli F, Grandi G, Anderson WF (2016) Crystal structures of the components of the Staphylococcus aureus leukotoxin ED. Acta Cryst D Struct Biol 72:113–120

    Article  CAS  Google Scholar 

  • Oganesyan V, Peng L, Damschroder MM, Cheng L, Sadowska A, Tkaczyk C, Sellman BR, Wu H, Dall’Acqua WF (2014) Mechanisms of neutralization of a human anti-alpha toxin antibody. J Biol Chem 289:29874–29880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Pédelacq JD, Maveyraud L, Prévost G, Baba-Moussa L, González 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

    Article  PubMed  Google Scholar 

  • Potrich C, Bastiani H, Colin DA, Huck S, Prévost G, Dalla Serra M (2009) The influence of membrane lipids in Staphylococcus aureus gamma-hemolysins pore formation. J Membr Biol 227:13–24

    Article  CAS  PubMed  Google Scholar 

  • Qiu J, Niu X, Dong J, Wang D, Wang J, Li H, Luo M, Li S, Feng H, Deng X (2012) Baicalin protects mice from Staphylococcus aureus pneumonia via inhibition of the cytolytic activity of -hemolysin. J Infect Dis 206:292–301

    Article  CAS  PubMed  Google Scholar 

  • Ramaro N, Sanchis V (2013) The pore-forming haemolysins of Bacillus cereus: a review. Toxins (Basel) 5:1119–1139

    Article  Google Scholar 

  • Reyes-Robles T, Alonzo F 3rd, 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

    Article  CAS  PubMed  Google Scholar 

  • Reyes-Robles T, Lubkin A, Alonzo F 3rd, Lacy DB, Torres VJ (2016) Exploiting dominant-negative toxins to combat Staphylococcus aureus pathogenesis. EMBO Rep 17:428–440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roblin P, Guillet V, Joubert O, Keller D, Erard M, Maveyraud L, Prévost G, Mourey L (2008) A covalent S-F heterodimer of leucotoxin reveals molecular plasticity of beta-barrel pore-forming toxins. Proteins 71:485–496

    Article  CAS  PubMed  Google Scholar 

  • Rouha H, Badarau A, Visram ZC, Battles MB, Prinz B, Magyarics Z, Nagy G, Mirkina I, Stulik L, Zerbs M, Jägerhofer M, Maierhofer B, Teubenbacher A, Dolezilkova I, Gross K, Banerjee S, Zauner G, Malafa S, Zmajkovic J, Maier S, Mabry R, Krauland E, Wittrup KD, Gerngross TU, Nagy E (2015) Five birds, one stone: neutralization of α-hemolysin and 4 bi-component leukocidins of Staphylococcus aureus with a single human monoclonal antibody. MAbs 7:243–254

    Article  CAS  PubMed  Google Scholar 

  • Rudolf M, Koch H, inventors; Kenta Biotech AG, assignee (2011) Human monoclonal antibody against Staphylococcus aureus derived alpha-toxin and its use in treating or preventing abscess formation patent. WO2011018208. 17 Feb 2011

    Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Spaan AN, Henry T, van Rooijen WJ, Perret M, Badiou C, Aerts PC, Kemmink J, de Haas CJ, van Kessel KP, Vandenesch F, Lina G, van Strijp JA (2013) The staphylococcal toxin Panton-Valentine leukocidin targets human C5a receptors. Cell Host Microbe 13:584–594

    Article  CAS  PubMed  Google Scholar 

  • Spaan AN, Surewaard BG, Nijland R, van Strijp JA (2014a) Neutrophils versus Staphylococcus aureus: a biological tug of war. Annu Rev Microbiol 67:629–650

    Article  Google Scholar 

  • Spaan AN, Vrieling M, Wallet P, Badiou C, Reyes-Robles T, Ohneck EA, Benito Y, de Haas CJ, Day CJ, Jennings MP, Lina G, Vandenesch F, van Kessel KP, Torres VJ, van Strijp JA, Henry T (2014b) The staphylococcal toxins γ-haemolysin AB and CB differentially target phagocytes by employing specific chemokine receptors. Nat Commun 5:5438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Spaan AN, Schiepers A, de Haas CJ, van Hooijdonk DD, Badiou C, Contamin H, Vandenesch F, Lina G, Gerard NP, Gerard C, van Kessel KP, Henry T, van Strijp JA (2014c) Differential interaction of the staphylococcal toxins Panton-Valentine leukocidin and γ-hemolysin CB with human C5a receptors. J Immunol 195:1034–1043

    Article  Google Scholar 

  • Spaan AN, Reyes-Robles T, Badiou C, Cochet S, Boguslawski KM, Yoong P, Day CJ, de Haas CJC, van Kessel KPM, Vandenesch F, Jennings MP, Le Van Kim C, Colin Y, van Strijp JA, Henry T, Torres VJ (2015) Staphylococcus aureus targets the Duffy antigen receptor for chemokines (DARC) to lyse erythrocytes. Cell Host Microbe 18:363–370

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Staphylococcus aureus toxoids phase 1–2 vaccine trial. https://clinicaltrials.gov/ct2/show/NCT01011335. Accessed 28 Oct 2016.

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Tanaka Y, Hirano N, Kaneko J, Kamio Y, Yao M, Tanaka I (2011) 2-Methyl-2,4-pentanediol induces spontaneous assembly of staphylococcal α-hemolysin into heptameric pore structure. Protein Sci 20:448–456

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tawk MY, Zimmermann-Meisse G, Bossu JL, Potrich C, Bourcier T, Dalla Serra M, Poulain B, Prévost G, Jover E (2015) Internalization of staphylococcal leukotoxins that bind and divert the C5a receptor is required for intracellular Ca2+ mobilization by human neutrophils. Cell Microbiol 17:1241–1257

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • von Eiff C, Friedrich AW, Peters G, Becker K (2004) Prevalence of genes encoding for members of the staphylococcal leukotoxin family among clinical isolates of Staphylococcus aureus. Diagn Microbiol Infect Dis 49:157–162

    Article  Google Scholar 

  • Wu Q, Guo Z (2010) Glycosylphosphatidylinositols are potential targets for the development of novel inhibitors for aerolysin-type of pore-forming bacterial toxins. Med Res Rev 30:258–269

    PubMed  Google Scholar 

  • 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 γ-hemolysin reveals the β-barrel pore formation mechanism by two components. Proc Natl Acad Sci U S A 108:17314–17319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Yokota K, Kamio Y (2000) Tyrosine 72 residue at the bottom of rim domain in LukF crucial for the sequential binding of the Staphylococcal γ-Hemolysin to human erythrocytes. Biosci Biotechnol Biochem 64:2744–2747

    Article  CAS  PubMed  Google Scholar 

  • Yoong P, Torres VJ (2015) Counter inhibition between leukotoxins attenuates Staphylococcus aureus virulence. Nat Commun 6:8125

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Christine Power for the critical reading of the manuscript.

Conflict of Interest

The authors declare potential conflict of interest being employees of the biotechnology company involved in this research work.

Author information

Authors and Affiliations

  1. Arsanis Biosciences, Campus Vienna Biocenter, Helmut-Qualtinger-Gasse 2, 1030, Vienna, Austria

    Adriana Badarau, Nikolina Trstenjak & Eszter Nagy

Authors
  1. Adriana Badarau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nikolina Trstenjak
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eszter Nagy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eszter Nagy .

Editor information

Editors and Affiliations

  1. Biochem and Mol Biol, Baylor College of Medicine, Houston, Texas, USA

    M. Zouhair Atassi

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Badarau, A., Trstenjak, N., Nagy, E. (2017). Structure and Function of the Two-Component Cytotoxins of Staphylococcus aureus – Learnings for Designing Novel Therapeutics. In: Atassi, M. (eds) Protein Reviews. Advances in Experimental Medicine and Biology(), vol 966. Springer, Singapore. https://doi.org/10.1007/5584_2016_200

Download citation

Publish with us

Policies and ethics

Search

Navigation