Exploiting dominant-negative toxins to combat Staphylococcus aureus pathogenesis

EMBO Reports

Volumn 17, Issue 3, 2016, Pages 428-440

  Reyes Robles, Tamara ^a   Lubkin, Ashira ^a   Alonzo, Francis ^a,c   Lacy, D Borden ^b   Torres, Victor J ^a  

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

^b VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c LOYOLA UNIVERSITY CHICAGO   (United States)

Author keywords

bi component; dominant negative; leukocidin; pore forming toxin; Staphylococcus aureus

Indexed keywords

GLYCINE; LEUKOCIDIN; CYTOTOXIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BACTERIAL LOAD; BLOODSTREAM INFECTION; CELL ASSAY; CHANNEL GATING; COMPLEX FORMATION; CONTROLLED STUDY; CYTOTOXICITY; FEMALE; HUMAN; IN VITRO STUDY; MOUSE; NEUTROPHIL; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN MOTIF; STAPHYLOCOCCUS AUREUS; STAPHYLOCOCCUS INFECTION; WILD TYPE; ANIMAL; CHEMISTRY; GENETICS; METABOLISM; MICROBIOLOGY; MUTATION; PATHOGENICITY; PHAGOCYTE; PROTEIN DOMAIN; PROTEIN MULTIMERIZATION; STAPHYLOCOCCAL INFECTIONS; VIRULENCE;

ANIMALS; CYTOTOXINS; FEMALE; GLYCINE; HUMANS; LEUKOCIDINS; MICE; MUTATION; NEUTROPHILS; PHAGOCYTES; PROTEIN DOMAINS; PROTEIN MULTIMERIZATION; STAPHYLOCOCCAL INFECTIONS; STAPHYLOCOCCUS AUREUS; VIRULENCE;

EID: 84959470571     PISSN: 1469221X     EISSN: 14693178     Source Type: Journal    
DOI: 10.15252/embr.201540994     Document Type: Article

References (54)

1. Chambers HF, Deleo FR, (2009) Waves of resistance: Staphylococcus aureus in the antibiotic era. Nat Rev Microbiol 7: 629-641
2. Nizet V, (2007) Understanding how leading bacterial pathogens subvert innate immunity to reveal novel therapeutic targets. J Allergy Clin Immunol 120: 13-22
3. Spaan AN, Surewaard BG, Nijland R, van Strijp JA, (2013) Neutrophils versus Staphylococcus aureus: a biological tug of war. Annu Rev Microbiol 67: 629-650
4. Alonzo F 3rd, Torres VJ, (2014) The bicomponent pore-forming leucocidins of Staphylococcus aureus. Microbiol Mol Biol Rev 78: 199-230
5. 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
6. 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
7. 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
8. 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
9. Yoong P, Torres VJ, (2013) The effects of Staphylococcus aureus leukotoxins on the host: cell lysis and beyond. Curr Opin Microbiol 16: 63-69
10. 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
11. 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
12. 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 USA 110: 10794-10799
13. 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
14. 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
15. Pier GB, (2013) Will there ever be a universal Staphylococcus aureus vaccine? Hum Vaccin Immunother 9: 1865-1876
16. David MZ, Daum RS, (2010) Community-associated methicillin-resistant Staphylococcus aureus: epidemiology and clinical consequences of an emerging epidemic. Clin Microbiol Rev 23: 616-687
17. Thammavongsa V, Kim HK, Missiakas D, Schneewind O, (2015) Staphylococcal manipulation of host immune responses. Nat Rev Microbiol 13: 529-543
18. Park S, Gerber S, Lee JC, (2014) Antibodies to Staphylococcus aureus serotype 8 capsular polysaccharide react with and protect against serotype 5 and 8 isolates. Infect Immun 82: 5049-5055
19. Fattom AI, Sarwar J, Ortiz A, Naso R, (1996) A Staphylococcus aureus capsular polysaccharide (CP) vaccine and CP-specific antibodies protect mice against bacterial challenge. Infect Immun 64: 1659-1665
20. Kim HK, Emolo C, DeDent AC, Falugi F, Missiakas DM, Schneewind O, (2012) Protein A-specific monoclonal antibodies and prevention of Staphylococcus aureus disease in mice. Infect Immun 80: 3460-3470
21. Kim HK, Cheng AG, Kim HY, Missiakas DM, Schneewind O, (2010) Nontoxigenic protein A vaccine for methicillin-resistant Staphylococcus aureus infections in mice. J Exp Med 207: 1863-1870
22. Kuklin NA, Clark DJ, Secore S, Cook J, Cope LD, McNeely T, Noble L, Brown MJ, Zorman JK, Wang XM, et al, (2006) A novel Staphylococcus aureus vaccine: iron surface determinant B induces rapid antibody responses in rhesus macaques and specific increased survival in a murine S. aureus sepsis model. Infect Immun 74: 2215-2223
23. Stranger-Jones YK, Bae T, Schneewind O, (2006) Vaccine assembly from surface proteins of Staphylococcus aureus. Proc Natl Acad Sci USA 103: 16942-16947
24. Vernachio J, Bayer AS, Le T, Chai YL, Prater B, Schneider A, Ames B, Syribeys P, Robbins J, Patti JM, (2003) Anti-clumping factor A immunoglobulin reduces the duration of methicillin-resistant Staphylococcus aureus bacteremia in an experimental model of infective endocarditis. Antimicrob Agents Chemother 47: 3400-3406
25. Schaffer AC, Solinga RM, Cocchiaro J, Portoles M, Kiser KB, Risley A, Randall SM, Valtulina V, Speziale P, Walsh E, et al, (2006) Immunization with Staphylococcus aureus clumping factor B, a major determinant in nasal carriage, reduces nasal colonization in a murine model. Infect Immun 74: 2145-2153
26. Sampedro GR, DeDent AC, Becker RE, Berube BJ, Gebhardt MJ, Cao H, Bubeck Wardenburg J, (2014) Targeting Staphylococcus aureus alpha-toxin as a novel approach to reduce severity of recurrent skin and soft-tissue infections. J Infect Dis 210: 1012-1018
27. Kennedy AD, Bubeck Wardenburg J, Gardner DJ, Long D, Whitney AR, Braughton KR, Schneewind O, DeLeo FR, (2010) Targeting of alpha-hemolysin by active or passive immunization decreases severity of USA300 skin infection in a mouse model. J Infect Dis 202: 1050-1058
28. Adhikari RP, Karauzum H, Sarwar J, Abaandou L, Mahmoudieh M, Boroun AR, Vu H, Nguyen T, Devi VS, Shulenin S, et al, (2012) Novel structurally designed vaccine for S. aureus alpha-hemolysin: protection against bacteremia and pneumonia. PLoS ONE 7: e38567
29. Delfani S, Mohabati Mobarez A, Imani Fooladi AA, Amani J, Emaneini M, (2015) Protection of mice against Staphylococcus aureus infection by a recombinant protein ClfA-IsdB-Hlg as a vaccine candidate. Med Microbiol Immunol 205: 47-55
30. 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
31. Aman MJ, Adhikari RP, (2014) Staphylococcal bicomponent pore-forming toxins: targets for prophylaxis and immunotherapy. Toxins (Basel) 6: 950-972
32. Karauzum H, Adhikari RP, Sarwar J, Devi VS, Abaandou L, Haudenschild C, Mahmoudieh M, Boroun AR, Vu H, Nguyen T, et al, (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
33. Laventie BJ, Rademaker HJ, Saleh M, de Boer E, Janssens R, Bourcier T, Subilia A, Marcellin L, van Haperen R, Lebbink JH, et al, (2011) Heavy chain-only antibodies and tetravalent bispecific antibody neutralizing Staphylococcus aureus leukotoxins. Proc Natl Acad Sci USA 108: 16404-16409
34. Fowler VG, Allen KB, Moreira ED, Moustafa M, Isgro F, Boucher HW, Corey GR, Carmeli Y, Betts R, Hartzel JS, et al, (2013) Effect of an investigational vaccine for preventing Staphylococcus aureus infections after cardiothoracic surgery: a randomized trial. JAMA 309: 1368-1378
35. Rupp ME, Holley HP Jr, Lutz J, Dicpinigaitis PV, Woods CW, Levine DP, Veney N, Fowler VG Jr, (2007) Phase II, randomized, multicenter, double-blind, placebo-controlled trial of a polyclonal anti-Staphylococcus aureus capsular polysaccharide immune globulin in treatment of Staphylococcus aureus bacteremia. Antimicrob Agents Chemother 51: 4249-4254
36. Moustafa M, Aronoff GR, Chandran C, Hartzel JS, Smugar SS, Galphin CM, Mailloux LU, Brown E, Dinubile MJ, Kartsonis NA, et al, (2012) Phase IIa study of the immunogenicity and safety of the novel Staphylococcus aureus vaccine V710 in adults with end-stage renal disease receiving hemodialysis. Clin Vaccine Immunol 19: 1509-1516
37. DuMont AL, Yoong P, Liu X, Day CJ, Chumbler NM, James DB, Alonzo F 3rd, 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
38. Diep BA, Gill SR, Chang RF, Phan TH, Chen JH, Davidson MG, Lin F, Lin J, Carleton HA, Mongodin EF, et al, (2006) Complete genome sequence of USA300, an epidemic clone of community-acquired meticillin-resistant Staphylococcus aureus. Lancet 367: 731-739
39. Deleo FR, Otto M, Kreiswirth BN, Chambers HF, (2010) Community-associated meticillin-resistant Staphylococcus aureus. Lancet 375: 1557-1568
40. Voyich JM, Braughton KR, Sturdevant DE, Whitney AR, Said-Salim B, Porcella SF, Long RD, Dorward DW, Gardner DJ, Kreiswirth BN, et al, (2005) Insights into mechanisms used by Staphylococcus aureus to avoid destruction by human neutrophils. J Immunol 175: 3907-3919
41. 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
42. Spaan AN, Schiepers A, de Haas CJ, van Hooijdonk DD, Badiou C, Contamin H, Vandenesch F, Lina G, Gerard NP, Gerard C, et al, (2015) Differential Interaction of the Staphylococcal Toxins Panton-Valentine Leukocidin and gamma-Hemolysin CB with Human C5a Receptors. J Immunol 195: 1034-1043
43. DuMont AL, Yoong P, Surewaard BG, Benson MA, Nijland R, van Strijp JA, Torres VJ, (2013) Staphylococcus aureus elaborates leukocidin AB to mediate escape from within human neutrophils. Infect Immun 81: 1830-1841
44. 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
45. 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
46. 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
47. Sellman BR, Mourez M, Collier RJ, (2001) Dominant-negative mutants of a toxin subunit: an approach to therapy of anthrax. Science 292: 695-697
48. Vinion-Dubiel AD, McClain MS, Czajkowsky DM, Iwamoto H, Ye D, Cao P, Schraw W, Szabo G, Blanke SR, Shao Z, et al, (1999) A dominant negative mutant of Helicobacter pylori vacuolating toxin (VacA) inhibits VacA-induced cell vacuolation. J Biol Chem 274: 37736-37742
49. 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
50. Alonzo F 3rd, 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
51. 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
52. 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
53. Holzinger D, Gieldon L, Mysore V, Nippe N, Taxman DJ, Duncan JA, Broglie PM, Marketon K, Austermann J, Vogl T, et al, (2012) Staphylococcus aureus Panton-Valentine leukocidin induces an inflammatory response in human phagocytes via the NLRP3 inflammasome. J Leukoc Biol 92: 1069-1081
54. Liang X, Yan M, Ji Y, (2009) The H35A mutated alpha-toxin interferes with cytotoxicity of staphylococcal alpha-toxin. Infect Immun 77: 977-983