Targeting Staphylococcus aureus toxins: A potential form of anti-virulence therapy

Toxins

Volumn 8, Issue 3, 2016, Pages

  Kong, Cin ^a   Neoh, Hui Min ^a   Nathan, Sheila ^a  

^a UNIVERSITI KEBANGSAAN MALAYSIA   (Malaysia)

Author keywords

Anti virulence therapy; Regulatory system; Staphylococcus aureus; Toxins; Virulence factors

Indexed keywords

ALPHA DEFENSIN; BACTERIAL TOXIN; BETA CYCLODEXTRIN DERIVATIVE; EXFOLIATIN; GI 254023X; HEMOLYSIN; IMMUNOGLOBULIN; LEUKOTOXIN; MONOCLONAL ANTIBODY 154; MONOCLONAL ANTIBODY 1A9; MONOCLONAL ANTIBODY 20B1; MONOCLONAL ANTIBODY 7B8; MONOCLONAL ANTIBODY HLA; MONOCLONAL ANTIBODY LTM14; MORIN; NEUTRALIZING ANTIBODY; OROXYLIN A; PANTON VALENTINE LEUKOCIDIN; SALAZOSULFAPYRIDINE; SMAD ANCHOR FOR RECEPTOR ACTIVATION; STAPHYLOCOCCUS AUREUS TOXIN; STAPHYLOCOCCUS ENTEROTOXIN B; TOXIC SHOCK SYNDROME TOXIN 1; UNCLASSIFIED DRUG; VARIABLE REGION OF THE T CELL RECEPTOR BETA PROTEIN; VIRULENCE FACTOR; ANTIINFECTIVE AGENT; TOXIN;

ANTIBIOTIC RESISTANCE; ANTIMICROBIAL THERAPY; BACTERIAL VIRULENCE; CAENORHABDITIS ELEGANS; CELL PROLIFERATION; CHEMICAL STRUCTURE; CRYSTALLOGRAPHY; DOWN REGULATION; GENE EXPRESSION; HUMAN; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PSEUDOMONAS AERUGINOSA; REVIEW; STAPHYLOCOCCUS AUREUS; TOXIN ANALYSIS; TRANSCRIPTION REGULATION; ANIMAL; CHEMISTRY; DRUG EFFECTS; METABOLISM; MICROBIOLOGY; PATHOGENICITY; VIRULENCE;

ANIMALS; ANTI-BACTERIAL AGENTS; CAENORHABDITIS ELEGANS; HUMANS; STAPHYLOCOCCUS AUREUS; TOXINS, BIOLOGICAL; VIRULENCE; VIRULENCE FACTORS;

EID: 84962528471     PISSN: None     EISSN: 20726651     Source Type: Journal    
DOI: 10.3390/toxins8030072     Document Type: Review

References (152)

1. Antibiotic Resistance Threats in the United States. 2013. Available online: http://www.cdc.gov/drugresistance/threat-report-2013/ (accessed on 11 November 2015).
2. Lowy, F.D. Staphylococcus aureus infections. N. Engl. J. Med. 1998, 339, 520-532. [CrossRef] [PubMed]
3. McAdow, M, DeDent, A.C, Emolo, C, Cheng, A.G, Kreiswirth, B.N, Missiakas, D.M, Schneewind, O. Coagulases as determinants of protective immune responses against Staphylococcus aureus. Infect. Immun. 2012, 80, 3389-3398. [CrossRef] [PubMed]
4. Jusko, M, Potempa, J, Kantyka, T, Bielecka, E, Miller, H.K, Kalinska, M, Dubin, G, Garred, P, Shaw, L.N, Blom, A.M. Staphylococcal proteases aid in evasion of the human complement system. J. Innate Immun. 2014, 6, 31-46. [CrossRef] [PubMed]
5. Foster, T.J, Geoghegan, J.A, Ganesh, V.K, Hook, M. Adhesion, invasion and evasion: The many functions of the surface proteins of Staphylococcus aureus. Nat. Rev. Microbiol. 2014, 12, 49-62. [CrossRef] [PubMed]
6. Vazquez, V, Liang, X, Horndahl, J.K, Ganesh, V.K, Smeds, E, Foster, T.J, Hook, M. Fibrinogen is a ligand for the Staphylococcus aureus microbial surface components recognizing adhesive matrix molecules (MSCRAMM) bone sialoprotein-binding protein (Bbp). J. Biol. Chem. 2011, 286, 29797-29805. [CrossRef] [PubMed]
7. Corrigan, R.M, Miajlovic, H, Foster, T.J. Surface proteins that promote adherence of Staphylococcus aureus to human desquamated nasal epithelial cells. BMC Microbiol. 2009, 9, 22. [CrossRef] [PubMed]
8. Zecconi, A, Scali, F. Staphylococcus aureus virulence factors in evasion from innate immune defenses in human and animal diseases. Immunol. Lett. 2013, 150, 12-22. [CrossRef] [PubMed]
9. Chavakis, T, Preissner, K.T, Herrmann, M. The anti-inflammatory activities of Staphylococcus aureus. Trends Immunol. 2007, 28, 408-418. [CrossRef] [PubMed]
10. Powers, M.E, Bubeck Wardenburg, J. Igniting the fire: Staphylococcus aureus virulence factors in the pathogenesis of sepsis. PLoS Pathog. 2014, 10, e1003871. [CrossRef] [PubMed]
11. Valeva, A, Walev, I, Pinkernell, M, Walker, B, Bayley, H, Palmer, M, Bhakdi, S. Transmembrane beta-barrel of staphylococcal alpha-toxin forms in sensitive but not in resistant cells. Proc. Natl. Acad. Sci. USA 1997, 94, 11607-11611. [CrossRef] [PubMed]
12. 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. [CrossRef] [PubMed]
13. Powers, M.E, Becker, R.E, Sailer, A, Turner, J.R, Bubeck Wardenburg, J. Synergistic action of Staphylococcus aureus alpha-toxin on platelets and myeloid lineage cells contributes to lethal sepsis. Cell. Host Microbe 2015, 17, 775-787. [CrossRef] [PubMed]
14. Walev, I, Weller, U, Strauch, S, Foster, T, Bhakdi, S. Selective killing of human monocytes and cytokine release provoked by sphingomyelinase (beta-toxin) of Staphylococcus aureus. Infect. Immun. 1996, 64, 2974-2979. [PubMed]
15. Vandenesch, F, Lina, G, Henry, T. Staphylococcus aureus hemolysins, bi-component leukocidins, and cytolytic peptides: A redundant arsenal of membrane-damaging virulence factors? Front. Cell. Infect. Microbiol. 2012, 2, 12. [CrossRef] [PubMed]
16. Meyer, F, Girardot, R, Piemont, Y, Prevost, G, Colin, D.A. Analysis of the specificity of Panton-Valentine leucocidin and gamma-hemolysin F component binding. Infect. Immun. 2009, 77, 266-273. [CrossRef] [PubMed]
17. Olson, R, Nariya, H, Yokota, K, Kamio, Y, Gouaux, E. Crystal structure of staphylococcal LukF delineates conformational changes accompanying formation of a transmembrane channel. Nat. Struct. Biol. 1999, 6, 134-140. [PubMed]
18. Verdon, J, Girardin, N, Lacombe, C, Berjeaud, J.M, Hechard, Y. Delta-hemolysin, an update on a membrane-interacting peptide. Peptides 2009, 30, 817-823. [CrossRef] [PubMed]
19. Surewaard, B.G, de Haas, C.J, Vervoort, F, Rigby, K.M, DeLeo, F.R, Otto, M, van Strijp, J.A, Nijland, R. Staphylococcal alpha-phenol soluble modulins contribute to neutrophil lysis after phagocytosis. Cell. Microbiol. 2013, 15, 1427-1437. [CrossRef] [PubMed]
20. Otto, M. Phenol-soluble modulins. Int. J. Med. Microbiol. 2014, 304, 164-169. [CrossRef] [PubMed]
21. Zivkovic, A, Sharif, O, Stich, K, Doninger, B, Biaggio, M, Colinge, J, Bilban, M, Mesteri, I, Hazemi, P, Lemmens-Gruber, R, et al. TLR 2 and CD14 mediate innate immunity and lung inflammation to staphylococcal Panton-Valentine leukocidin in vivo. J. Immunol. 2011, 186, 1608-1617. [CrossRef] [PubMed]
22. Inden, K, Kaneko, J, Miyazato, A, Yamamoto, N, Mouri, S, Shibuya, Y, Nakamura, K, Aoyagi, T, Hatta, M, Kunishima, H, et al. Toll-like receptor 4-dependent activation of myeloid dendritic cells by leukocidin of Staphylococcus aureus. Microbes Infect. 2009, 11, 245-253. [CrossRef] [PubMed]
23. Alonzo, F., III; Kozhaya, L, Rawlings, S.A, Reyes-Robles, T, DuMont, A.L, Myszka, D.G, Landau, N.R, Unutmaz, D, Torres, V.J. CCR5 is a receptor for Staphylococcus aureus leukotoxin ED. Nature 2013, 493, 51-55. [PubMed]
24. DuMont, A.L, Yoong, P, Day, C.J, Alonzo, F., III; McDonald, W.H, Jennings, M.P, Torres, V.J. Staphylococcus aureus LukAB cytotoxin kills human neutrophils by targeting the CD11b subunit of the integrin Mac-1. Proc. Natl. Acad. Sci. USA 2013, 110, 10794-10799. [PubMed]
25. Spaan, A.N, Henry, T, van Rooijen, W.J, Perret, M, Badiou, C, Aerts, P.C, Kemmink, J, de Haas, C.J, van Kessel, K.P, Vandenesch, F, et al. The staphylococcal toxin Panton-Valentine leukocidin targets human C5a receptors. Cell. Host Microbe 2013, 13, 584-594. [CrossRef] [PubMed]
26. Otto, M. Basis of virulence in community-associated methicillin-resistant Staphylococcus aureus. Annu. Rev. Microbiol. 2010, 64, 143-162. [CrossRef] [PubMed]
27. Bukowski, M, Wladyka, B, Dubin, G. Exfoliative toxins of Staphylococcus aureus. Toxins 2010, 2, 1148-1165. [CrossRef] [PubMed]
28. Eyre, R.W, Stanley, J.R. Human autoantibodies against a desmosomal protein complex with a calcium-sensitive epitope are characteristic of pemphigus foliaceus patients. J. Exp. Med. 1987, 165, 1719-1724. [CrossRef] [PubMed]
29. Hanakawa, Y, Schechter, N.M, Lin, C, Garza, L, Li, H, Yamaguchi, T, Fudaba, Y, Nishifuji, K, Sugai, M, Amagai, M, et al. Molecular mechanisms of blister formation in bullous impetigo and staphylococcal scalded skin syndrome. J. Clin. Invest. 2002, 110, 53-60. [CrossRef] [PubMed]
30. Monday, S.R, Vath, G.M, Ferens, W.A, Deobald, C, Rago, J.V, Gahr, P.J, Monie, D.D, Iandolo, J.J, Chapes, S.K, Davis, W.C, et al. Unique superantigen activity of staphylococcal exfoliative toxins. J. Immunol. 1999, 162, 4550-4559. [PubMed]
31. Hennekinne, J.A, De Buyser, M.L, Dragacci, S. Staphylococcus aureus and its food poisoning toxins: Characterization and outbreak investigation. FEMS Microbiol. Rev. 2012, 36, 815-836. [CrossRef] [PubMed]
32. Lin, C.F, Chen, C.L, Huang, W.C, Cheng, Y.L, Hsieh, C.Y, Wang, C.Y, Hong, M.Y. Different types of cell death induced by enterotoxins. Toxins 2010, 2, 2158-2176. [CrossRef] [PubMed]
33. Balaban, N, Rasooly, A. Staphylococcal enterotoxins. Int. J. Food Microbiol. 2000, 61, 1-10. [CrossRef]
34. Betley, M.J, Schlievert, P.M, Bergdoll, M.S, Bohach, G.A, Iandolo, J.J, Khan, S.A, Pattee, P.A, Reiser, R.R. Staphylococcal gene nomenclature. ASM News 1990, 56, 182.
35. Berkley, S.F, Hightower, A.W, Broome, C.V, Reingold, A.L. The relationship of tampon characteristics to menstrual toxic shock syndrome. JAMA 1987, 258, 917-920. [CrossRef] [PubMed]
36. Otto, M. Staphylococcus aureus toxins. Curr. Opin. Microbiol. 2014, 17, 32-37. [CrossRef] [PubMed]
37. Stach, C.S, Herrera, A, Schlievert, P.M. Staphylococcal superantigens interact with multiple host receptors to cause serious diseases. Immunol. Res. 2014, 59, 177-181. [CrossRef] [PubMed]
38. Larkin, S.M, Williams, D.N, Osterholm, M.T, Tofte, R.W, Posalaky, Z. Toxic shock syndrome: Clinical, laboratory, and pathologic findings in nine fatal cases. Ann. Intern. Med. 1982, 96, 858-864. [CrossRef] [PubMed]
39. 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. [CrossRef] [PubMed]
40. Roux, A, Todd, D.A, Velazquez, J.V, Cech, N.B, Sonenshein, A.L. Cody-mediated regulation of the Staphylococcus aureus Agr system integrates nutritional and population density signals. J. Bacteriol. 2014, 196, 1184-1196. [CrossRef] [PubMed]
41. Cheung, A.L, Koomey, J.M, Butler, C.A, Projan, S.J, Fischetti, V.A. Regulation of exoprotein expression in Staphylococcus aureus by a locus (sar) distinct from agr. Proc. Natl. Acad. Sci. USA 1992, 89, 6462-6466. [CrossRef] [PubMed]
42. Giraudo, A.T, Cheung, A.L, Nagel, R. The sae locus of Staphylococcus aureus controls exoprotein synthesis at the transcriptional level. Arch. Microbiol. 1997, 168, 53-58. [CrossRef] [PubMed]
43. Gaskill, M.E, Khan, S.A. Regulation of the enterotoxin B gene in Staphylococcus aureus. J. Biol. Chem. 1988, 263, 6276-6280. [PubMed]
44. Bayles, K.W, Iandolo, J.J. Genetic and molecular analyses of the gene encoding staphylococcal enterotoxin D. J. Bacteriol 1989, 171, 4799-4806. [PubMed]
45. Regassa, L.B, Couch, J.L, Betley, M.J. Steady-state staphylococcal enterotoxin type C mRNA is affected by a product of the accessory gene regulator (agr) and by glucose. Infect. Immun. 1991, 59, 955-962. [PubMed]
46. Vojtov, N, Ross, H.F, Novick, R.P. Global repression of exotoxin synthesis by staphylococcal superantigens. Proc. Natl. Acad. Sci. USA 2002, 99, 10102-10107. [CrossRef] [PubMed]
47. Mallonee, D.H, Glatz, B.A, Pattee, P.A. Chromosomal mapping of a gene affecting enterotoxin A production in Staphylococcus aureus. Appl. Environ. Microbiol. 1982, 43, 397-402. [PubMed]
48. Kreiswirth, B.N, Lofdahl, S, Betley, M.J, O’Reilly, M, Schlievert, P.M, Bergdoll, M.S, Novick, R.P. The toxic shock syndrome exotoxin structural gene is not detectably transmitted by a prophage. Nature 1983, 305, 709-712. [CrossRef] [PubMed]
49. Arvidson, S, Tegmark, K. Regulation of virulence determinants in Staphylococcus aureus. Int J. Med. Microbiol. 2001, 291, 159-170. [CrossRef] [PubMed]
50. Said-Salim, B, Dunman, P.M, McAleese, F.M, Macapagal, D, Murphy, E, McNamara, P.J, Arvidson, S, Foster, T.J, Projan, S.J, Kreiswirth, B.N. Global regulation of Staphylococcus aureus genes by Rot. J. Bacteriol. 2003, 185, 610-619. [CrossRef] [PubMed]
51. Smeltzer, M.S, Hart, M.E, Iandolo, J.J. Phenotypic characterization of xpr, a global regulator of extracellular virulence factors in Staphylococcus aureus. Infect. Immun. 1993, 61, 919-925. [PubMed]
52. Dunman, P.M, Murphy, E, Haney, S, Palacios, D, Tucker-Kellogg, G, Wu, S, Brown, E.L, Zagursky, R.J, Shlaes, D, Projan, S.J. Transcription profiling-based identification of Staphylococcus aureus genes regulated by the agr and/or sarA loci. J. Bacteriol. 2001, 183, 7341-7353. [CrossRef] [PubMed]
53. Novick, R.P, Projan, S.J, Kornblum, J, Ross, H.F, Ji, G, Kreiswirth, B, Vandenesch, F, Moghazeh, S. The agr P2 operon: An autocatalytic sensory transduction system in Staphylococcus aureus. Mol. Gen. Genet. 1995, 248, 446-458. [CrossRef] [PubMed]
54. Thoendel, M, Horswill, A.R. Identification of Staphylococcus aureus AgrD residues required for autoinducing peptide biosynthesis. J. Biol. Chem. 2009, 284, 21828-21838. [CrossRef] [PubMed]
55. 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. [CrossRef] [PubMed]
56. 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. [PubMed]
57. 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. [CrossRef] [PubMed]
58. Queck, S.Y, Jameson-Lee, M, Villaruz, A.E, Bach, T.H, Khan, B.A, Sturdevant, D.E, Ricklefs, S.M, Li, M, Otto, M. RNAIII-independent target gene control by the agr quorum-sensing system: Insight into the evolution of virulence regulation in Staphylococcus aureus. Mol. Cell. 2008, 32, 150-158. [CrossRef] [PubMed]
59. Balaban, N, Novick, R.P. Translation ofRNAIII, the Staphylococcus aureus agr regulatory RNA molecule, can be activated by a 3’-end deletion. FEMS Microbiol. Lett. 1995, 133, 155-161. [PubMed]
60. Giraudo, A.T, Calzolari, A, Cataldi, A.A, Bogni, C, Nagel, R. The sae locus of Staphylococcus aureus encodes a two-component regulatory system. FEMS Microbiol. Lett. 1999, 177, 15-22. [CrossRef] [PubMed]
61. Voyich, J.M, Vuong, C, DeWald, M, Nygaard, T.K, Kocianova, S, Griffith, S, Jones, J, Iverson, C, Sturdevant, D.E, Braughton, K.R, et al. The SaeR/S gene regulatory system is essential for innate immune evasion by Staphylococcus aureus. J. Infect. Dis. 2009, 199, 1698-1706. [CrossRef] [PubMed]
62. Date, S.V, Modrusan, Z, Lawrence, M, Morisaki, J.H, Toy, K, Shah, I.M, Kim, J, Park, S, Xu, M, Basuino, L, et al. Global gene expression of methicillin-resistant Staphylococcus aureus USA300 during human and mouse infection. J. Infect. Dis. 2014, 209, 1542-1550. [CrossRef] [PubMed]
63. Giraudo, A.T, Raspanti, C.G, Calzolari, A, Nagel, R. Characterization of a Tn551-mutant of Staphylococcus aureus defective in the production of several exoproteins. Can. J. Microbiol. 1994, 40, 677-681. [CrossRef] [PubMed]
64. Cassat, J.E, Hammer, N.D, Campbell, J.P, Benson, M.A, Perrien, D.S, Mrak, L.N, Smeltzer, M.S, Torres, V.J, Skaar, E.P. A secreted bacterial protease tailors the Staphylococcus aureus virulence repertoire to modulate bone remodeling during osteomyelitis. Cell. Host Microbe 2013, 13, 759-772. [CrossRef] [PubMed]
65. Novick, R.P, Jiang, D. The staphylococcal saeRS system coordinates environmental signals with agr quorum sensing. Microbiology 2003, 149, 2709-2717. [CrossRef] [PubMed]
66. Rogasch, K, Ruhmling, V, Pane-Farre, J, Hoper, D, Weinberg, C, Fuchs, S, Schmudde, M, Broker, B.M, Wolz, C, Hecker, M, et al. Influence of the two-component system SaeRS on global gene expression in two different Staphylococcus aureus strains. J. Bacteriol. 2006, 188, 7742-7758. [CrossRef] [PubMed]
67. Novick, R.P. Autoinduction and signal transduction in the regulation of staphylococcal virulence. Mol. Microbiol. 2003, 48, 1429-1449. [CrossRef] [PubMed]
68. Bronner, S, Monteil, H, Prevost, G. Regulation of virulence determinants in Staphylococcus aureus: Complexity and applications. FEMS Microbiol. Rev. 2004, 28, 183-200. [CrossRef] [PubMed]
69. Beenken, K.E, Blevins, J.S, Smeltzer, M.S. Mutation of sarA in Staphylococcus aureus limits biofilm formation. Infect. Immun. 2003, 71, 4206-4211. [CrossRef] [PubMed]
70. Lamichhane-Khadka, R, Cantore, S.A, Riordan, J.T, Delgado, A, Norman, A.E, Duenas, S, Zaman, S, Horan, S, Wilkinson, B.J, Gustafson, J.E. SarA inactivation reduces vancomycin-intermediate and ciprofloxacin resistance expression by Staphylococcus aureus. Int. J. Antimicrob. Agents 2009, 34, 136-141. [CrossRef] [PubMed]
71. Bayer, M.G, Heinrichs, J.H, Cheung, A.L. The molecular architecture of the sar locus in Staphylococcus aureus. J. Bacteriol 1996, 178, 4563-4570. [PubMed]
72. Chien, Y, Manna, A.C, Projan, S.J, Cheung, A.L. SarA, a global regulator of virulence determinants in Staphylococcus aureus, binds to a conserved motif essential for sar-dependent gene regulation. J. Biol. Chem. 1999, 274, 37169-37176. [CrossRef] [PubMed]
73. Cheung, A.L, Bayer, M.G, Heinrichs, J.H. Sar genetic determinants necessary for transcription of RNAII and RNAIII in the agr locus of Staphylococcus aureus. J. Bacteriol. 1997, 179, 3963-3971. [PubMed]
74. 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. [CrossRef] [PubMed]
75. 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. [CrossRef] [PubMed]
76. Blevins, J.S, Elasri, M.O, Allmendinger, S.D, Beenken, K.E, Skinner, R.A, Thomas, J.R, Smeltzer, M.S. Role of sarA in the pathogenesis of Staphylococcus aureus musculoskeletal infection. Infect. Immun. 2003, 71, 516-523. [CrossRef] [PubMed]
77. Snowden, J.N, Beaver, M, Beenken, K, Smeltzer, M, Horswill, A.R, Kielian, T. Staphylococcus aureus sarA regulates inflammation and colonization during central nervous system biofilm formation. PLoS ONE 2013, 8, e84089. [CrossRef] [PubMed]
78. Wu, S, de Lencastre, H, Tomasz, A. Sigma-B, a putative operon encoding alternate sigma factor of Staphylococcus aureus RNA polymerase: Molecular cloning and DNA sequencing. J. Bacteriol. 1996, 178, 6036-6042. [PubMed]
79. Zhang, S, Reeves, A, Woodbury, R.L, Haldenwang, W.G. Coexpression patterns of sigma(B) regulators in Bacillus subtilis affect sigma(B) inducibility. J. Bacteriol. 2005, 187, 8520-8525. [CrossRef] [PubMed]
80. Andrey, D.O, Jousselin, A, Villanueva, M, Renzoni, A, Monod, A, Barras, C, Rodriguez, N, Kelley,W.L. Impact of the regulators sigB, rot, sarA and sarS on the toxic shock Tst promoter and TSST-1 expression in Staphylococcus aureus. PLoS ONE 2015, 10, e0135579. [CrossRef] [PubMed]
81. Ziebandt, A.K, Weber, H, Rudolph, J, Schmid, R, Hoper, D, Engelmann, S, Hecker, M. Extracellular proteins of Staphylococcus aureus and the role of sarA and sigma B. Proteomics 2001, 1, 480-493. [CrossRef]
82. Schmidt, K.A, Donegan, N.P, Kwan, W.A., Jr., Cheung, A. Influences of sigma B and agr on expression of staphylococcal enterotoxin B (seb) in Staphylococcus aureus. Can. J. Microbiol. 2004, 50, 351-360. [CrossRef] [PubMed]
83. Jonsson, I.M, Arvidson, S, Foster, S, Tarkowski, A. Sigma factor B and RsbU are required for virulence in Staphylococcus aureus-induced arthritis and sepsis. Infect. Immun. 2004, 72, 6106-6111. [CrossRef] [PubMed]
84. Tuchscherr, L, Bischoff, M, Lattar, S.M, Noto Llana, M, Pfortner, H, Niemann, S, Geraci, J, Van de Vyver, H, Fraunholz, M.J, Cheung, A.L, et al. Sigma factor sigB is crucial to mediate Staphylococcus aureus adaptation during chronic infections. PLoS Pathog. 2015, 11, e1004870. [CrossRef] [PubMed]
85. Blaser, M. Antibiotic overuse: Stop the killing of beneficial bacteria. Nature 2011, 476, 393-394. [CrossRef] [PubMed]
86. World Antibiotic Awareness Week. Available online: http://www.who.int/mediacentre/events/2015/world-antibiotic-awareness-week/event/en/ (accessed on 24 December 2015).
87. Rasko, D.A, Sperandio, V. Anti-virulence strategies to combat bacteria-mediated disease. Nat. Rev. Drug Discov. 2010, 9, 117-128. [CrossRef] [PubMed]
88. Mellbye, B, Schuster, M. The sociomicrobiology of antivirulence drug resistance: A proof of concept. MBio 2011, 2. [CrossRef] [PubMed]
89. Allen, R.C, Popat, R, Diggle, S.P, Brown, S.P. Targeting virulence: Can we make evolution-proof drugs? Nat. Rev. Microbiol. 2014, 12, 300-308. [CrossRef] [PubMed]
90. Ragle, B.E, Bubeck Wardenburg, J. Anti-alpha-hemolysin monoclonal antibodies mediate protection against Staphylococcus aureus pneumonia. Infect. Immun. 2009, 77, 2712-2718. [CrossRef] [PubMed]
91. Hua, L, Hilliard, J.J, Shi, Y, Tkaczyk, C, Cheng, L.I, Yu, X, Datta, V, Ren, S, Feng, H, Zinsou, R, et al. Assessment of an anti-alpha-toxin monoclonal antibody for prevention and treatment of Staphylococcus aureus-induced pneumonia. Antimicrob. Agents Chemother. 2014, 58, 1108-1117. [CrossRef] [PubMed]
92. Tkaczyk, C, Hua, L, Varkey, R, Shi, Y, Dettinger, L, Woods, R, Barnes, A, MacGill, R.S, Wilson, S, Chowdhury, P, et al. 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. [CrossRef] [PubMed]
93. Foletti, D, Strop, P, Shaughnessy, L, Hasa-Moreno, A, Casas, M.G, Russell, M, Bee, C, Wu, S, Pham, A, Zeng, Z, et al. Mechanism of action and in vivo efficacy of a human-derived antibody against Staphylococcus aureus alpha-hemolysin. J. Mol. Biol. 2013, 425, 1641-1654. [CrossRef] [PubMed]
94. Pooja, J, Ajit, S. Staphylococcus aureus-hemolysin-neutralizing single-domain antibody isolated from phage display library of indian desert camel. Asian Pac. J. Trop Med. 2010, 3, 1-7.
95. Rouha, H, Badarau, A, Visram, Z.C, Battles, M.B, Prinz, B, Magyarics, Z, Nagy, G, Mirkina, I, Stulik, L, Zerbs, M, et al. Five birds, one stone: Neutralization of alpha-hemolysin and 4 bi-component leukocidins of Staphylococcus aureus with a single human monoclonal antibody. MAbs 2015, 7, 243-254. [CrossRef] [PubMed]
96. Karginov, V.A, Nestorovich, E.M, Schmidtmann, F, Robinson, T.M, Yohannes, A, Fahmi, N.E, Bezrukov, S.M, Hecht, S.M. Inhibition of S. aureus alpha-hemolysin and B. anthracis lethal toxin by beta-cyclodextrin derivatives. Bioorg. Med. Chem. 2007, 15, 5424-5431. [CrossRef] [PubMed]
97. McCormick, C.C, Caballero, A.R, Balzli, C.L, Tang, A, O’Callaghan, R.J. Chemical inhibition of alpha-toxin, a key corneal virulence factor of Staphylococcus aureus. Invest. Ophthalmol. Vis. Sci. 2009, 50, 2848-2854. [CrossRef] [PubMed]
98. 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. [CrossRef] [PubMed]
99. Dong, J, Qiu, J, Zhang, Y, Lu, C, Dai, X, Wang, J, Li, H, Wang, X, Tan, W, Luo, M, et al. Oroxylin a inhibits hemolysis via hindering the self-assembly of alpha-hemolysin heptameric transmembrane pore. PLoS Comput. Biol. 2013, 9, e1002869. [CrossRef] [PubMed]
100. Qiu, J, Wang, D, Zhang, Y, Dong, J, Wang, J, Niu, X. Molecular modeling reveals the novel inhibition mechanism and binding mode of three natural compounds to staphylococcal alpha-hemolysin. PLoS ONE 2013, 8, e80197. [CrossRef] [PubMed]
101. Melo, M.C, Teixeira, L.R, Pol-Fachin, L, Rodrigues, C.G. Inhibition of the hemolytic activity caused by Staphylococcus aureus alpha-hemolysin through isatin-schiff copper(ii) complexes. FEMS Microbiol. Lett. 2016, 363.
102. Wang, J, Zhou, X, Liu, S, Li, G, Shi, L, Dong, J, Li, W, Deng, X, Niu, X. Morin hydrate attenuates Staphylococcus aureus virulence by inhibiting the self-assembly of alpha-hemolysin. J. Appl. Microbiol. 2015, 118, 753-763. [CrossRef] [PubMed]
103. Rashidieh, B, Etemadiafshar, S, Memari, G, Mirzaeichegeni, M, Yazdi, S, Farsimadan, F, Alizadeh, S. A molecular modeling based screening for potential inhibitors to alpha hemolysin from Staphylococcus aureus. Bioinformation 2015, 11, 373-377. [CrossRef] [PubMed]
104. Rani, N, Saravanan, V, Lakshmi, P.T.V, Annamalai, A. Inhibition of pore formation by blocking the assembly of Staphylococcus aureus -hemolysin through a novel peptide inhibitor: An in silico approach. Int. J. Pept. Res. Ther. 2014, 20, 575-583. [CrossRef]
105. Dreymueller, D, Uhlig, S, Ludwig, A. Adam-family metalloproteinases in lung inflammation: Potential therapeutic targets. Am. J. Physiol Lung Cell. Mol. Physiol. 2015, 308, L325-343. [CrossRef] [PubMed]
106. Sampedro, G.R, DeDent, A.C, Becker, R.E, Berube, B.J, Gebhardt, M.J, Cao, H, Bubeck Wardenburg J. Targeting Staphylococcus aureus alpha-toxin as a novel approach to reduce severity of recurrent skin and soft-tissue infections. J. Infect. Dis. 2014, 210, 1012-1018. [CrossRef] [PubMed]
107. Gauduchon, V, Cozon, G, Vandenesch, F, Genestier, A.L, Eyssade, N, Peyrol, S, Etienne, J, Lina, G. Neutralization of Staphylococcus aureus Panton-Valentine leukocidin by intravenous immunoglobulin in vitro. J. Infect. Dis. 2004, 189, 346-353. [CrossRef] [PubMed]
108. Mairpady Shambat, S, Chen, P, Nguyen Hoang, A.T, Bergsten, H, Vandenesch, F, Siemens, N, Lina, G, Monk, I.R, Foster, T.J, Arakere, G, et al. Modelling staphylococcal pneumonia in a human 3D lung tissue model system delineates toxin-mediated pathology. Dis. Model. Mech. 2015, 8, 1413-1425. [CrossRef] [PubMed]
109. Rouzic, N, Janvier, F, Libert, N, Javouhey, E, Lina, G, Nizou, J.Y, Pasquier, P, Stamm, D, Brinquin, L, Pelletier, C, et al. Prompt and successful toxin-targeting treatment of three patients with necrotizing pneumonia due to Staphylococcus aureus strains carrying the Panton-Valentine leukocidin genes. J. Clin. Microbiol. 2010, 48, 1952-1955. [CrossRef] [PubMed]
110. Laventie, B.J, Rademaker, H.J, Saleh, M, de Boer, E, Janssens, R, Bourcier, T, Subilia, A, Marcellin, L, van Haperen, R, Lebbink, J.H, et al. Heavy chain-only antibodies and tetravalent bispecific antibody neutralizing Staphylococcus aureus leukotoxins. Proc. Natl. Acad. Sci. USA 2011, 108, 16404-16409. [CrossRef] [PubMed]
111. Karauzum, H, Adhikari, R.P, Sarwar, J, Devi, V.S, Abaandou, L, Haudenschild, C, Mahmoudieh, M, Boroun, A.R, Vu, H, Nguyen, T, et al. Structurally designed attenuated subunit vaccines for S. aureus LukS-PV and LukF-PV confer protection in a mouse bacteremia model. PLoS ONE 2013, 8, e65384. [CrossRef] [PubMed]
112. Adhikari, R.P, Kort, T, Shulenin, S, Kanipakala, T, Ganjbaksh, N, Roghmann, M.C, Holtsberg, F.W, Aman, M.J. Antibodies to S. aureus LukS-PV attenuated subunit vaccine neutralize a broad spectrum of canonical and non-canonical bicomponent leukotoxin pairs. PLoS ONE 2015, 10, e0137874. [CrossRef] [PubMed]
113. Vandenesch, F, Naimi, T, Enright, M.C, Lina, G, Nimmo, G.R, Heffernan, H, Liassine, N, Bes, M, Greenland, T, Reverdy, M.E, et al. Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: Worldwide emergence. Emerg. Infect. Dis. 2003, 9, 978-984. [CrossRef] [PubMed]
114. Diep, B.A, Otto, M. The role of virulence determinants in community-associated MRSA pathogenesis. Trends Microbiol. 2008, 16, 361-369. [CrossRef] [PubMed]
115. Hermos, C.R, Yoong, P, Pier, G.B. High levels of antibody to Panton-Valentine leukocidin are not associated with resistance to Staphylococcus aureus-associated skin and soft-tissue infection. Clin. Infect. Dis. 2010, 51, 1138-1146. [CrossRef] [PubMed]
116. Cardot-Martin, E, Casalegno, J.S, Badiou, C, Dauwalder, O, Keller, D, Prevost, G, Rieg, S, Kern, W.V, Cuerq, C, Etienne, J, et al. Alpha-defensins partially protect human neutrophils against Panton-Valentine leukocidin produced by Staphylococcus aureus. Lett. Appl. Microbiol. 2015, 61, 158-164. [CrossRef] [PubMed]
117. Pinchuk, I.V, Beswick, E.J, Reyes, V.E. Staphylococcal enterotoxins. Toxins 2010, 2, 2177-2197. [CrossRef] [PubMed]
118. Marrack, P, Blackman, M, Kushnir, E, Kappler, J. The toxicity of staphylococcal enterotoxin B in mice is mediated by t cells. J. Exp. Med. 1990, 171, 455-464. [CrossRef] [PubMed]
119. Drozdowski, B, Zhou, Y, Kline, B, Spidel, J, Chan, Y.Y, Albone, E, Turchin, H, Chao, Q, Henry, M, Balogach, J, et al. Generation and characterization of high affinity human monoclonal antibodies that neutralize staphylococcal enterotoxin B. J. Immune Based Ther. Vaccines 2010, 8, 9. [CrossRef] [PubMed]
120. Tilahun, M.E, Rajagopalan, G, Shah-Mahoney, N, Lawlor, R.G, Tilahun, A.Y, Xie, C, Natarajan, K, Margulies, D.H, Ratner, D.I, Osborne, B.A, et al. Potent neutralization of staphylococcal enterotoxin B by synergistic action of chimeric antibodies. Infect. Immun. 2010, 78, 2801-2811. [CrossRef] [PubMed]
121. Dutta, K, Varshney, A.K, Franklin, M.C, Goger, M, Wang, X, Fries, B.C. Mechanisms mediating enhanced neutralization efficacy of staphylococcal enterotoxin B by combinations of monoclonal antibodies. J. Biol. Chem. 2015, 290, 6715-6730. [CrossRef] [PubMed]
122. Varshney, A.K, Wang, X, Scharff, M.D, MacIntyre, J, Zollner, R.S, Kovalenko, O.V, Martinez, L.R, Byrne, F.R, Fries, B.C. Staphylococcal enterotoxin B-specific monoclonal antibody 20B1 successfully treats diverse Staphylococcus aureus infections. J. Infect. Dis. 2013, 208, 2058-2066. [CrossRef] [PubMed]
123. Varshney, A.K, Wang, X, Cook, E, Dutta, K, Scharff, M.D, Goger, M.J, Fries, B.C. Generation, characterization, and epitope mapping of neutralizing and protective monoclonal antibodies against staphylococcal enterotoxin B-induced lethal shock. J. Biol. Chem. 2011, 286, 9737-9747. [CrossRef] [PubMed]
124. Buonpane, R.A, Churchill, H.R, Moza, B, Sundberg, E.J, Peterson, M.L, Schlievert, P.M, Kranz, D.M. Neutralization of staphylococcal enterotoxin B by soluble, high-affinity receptor antagonists. Nat. Med. 2007, 13, 725-729. [CrossRef] [PubMed]
125. Yang, X, Buonpane, R.A, Moza, B, Rahman, A.K, Wang, N, Schlievert, P.M, McCormick, J.K, Sundberg, E.J, Kranz, D.M. Neutralization of multiple staphylococcal superantigens by a single-chain protein consisting of affinity-matured, variable domain repeats. J. Infect. Dis. 2008, 198, 344-348. [CrossRef] [PubMed]
126. Krakauer, T. Sulfasalazine attenuates staphylococcal enterotoxin B-induced immune responses. Toxins 2015, 7, 553-559. [CrossRef] [PubMed]
127. Balaban, N, Collins, L.V, Cullor, J.S, Hume, E.B, Medina-Acosta, E, Vieira da Motta, O, O’Callaghan, R, Rossitto, P.V, Shirtliff, M.E, Serafim da Silveira, L, et al. Prevention of diseases caused by Staphylococcus aureus using the peptide RIP. Peptides 2000, 21, 1301-1311. [CrossRef]
128. Gov, Y, Bitler, A, Dell’Acqua, G, Torres, J.V, Balaban, N. RNAIII inhibiting peptide (RIP), a global inhibitor of Staphylococcus aureus pathogenesis: Structure and function analysis. Peptides 2001, 22, 1609-1620. [CrossRef]
129. Ma, B, Zhou, Y, Li, M, Yu, Q, Xue, X, Li, Z, Da, F, Hou, Z, Luo, X. RIP-V improves murine survival in a sepsis model by down-regulating RNAIII expression and alpha-hemolysin release of methicillin-resistant Staphylococcus aureus. Pharmazie 2015, 70, 81-87. [PubMed]
130. Giacometti, A, Cirioni, O, Ghiselli, R, Dell’Acqua, G, Orlando, F, D’Amato, G, Mocchegiani, F, Silvestri, C, Del Prete, M.S, Rocchi, M, et al. RNAIII-inhibiting peptide improves efficacy of clinically used antibiotics in a murine model of staphylococcal sepsis. Peptides 2005, 26, 169-175. [CrossRef] [PubMed]
131. Simonetti, O, Cirioni, O, Ghiselli, R, Goteri, G, Scalise, A, Orlando, F, Silvestri, C, Riva, A, Saba, V, Madanahally, K.D, et al. RNAIII-inhibiting peptide enhances healing of wounds infected with methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 2008, 52, 2205-2211. [CrossRef] [PubMed]
132. Jiang, L, Li, H, Wang, L, Song, Z, Shi, L, Li, W, Deng, X, Wang, J. Isorhamnetin attenuates Staphylococcus aureus-induced lung cell injury by inhibiting alpha-hemolysin expression. J. Microbiol. Biotechnol. 2015.
133. Wang, J, Qiu, J, Dong, J, Li, H, Luo, M, Dai, X, Zhang, Y, Leng, B, Niu, X, Zhao, S, et al. Chrysin protects mice from Staphylococcus aureus pneumonia. J. Appl. Microbiol. 2011, 111, 1551-1558. [CrossRef] [PubMed]
134. Tang, F, Li, W.H, Zhou, X, Liu, Y.H, Li, Z, Tang, Y.S, Kou, X, Wang, S.D, Bao, M, Qu, L.D, et al. Puerarin protects against Staphylococcus aureus-induced injury of human alveolar epithelial aA49 cells via downregulating alpha-hemolysin secretion. Microb. Drug Resist. 2014, 20, 357-363. [CrossRef] [PubMed]
135. Qiu, J, Niu, X, Wang, J, Xing, Y, Leng, B, Dong, J, Li, H, Luo, M, Zhang, Y, Dai, X, et al. Capsaicin protects mice from community-associated methicillin-resistant Staphylococcus aureus pneumonia. PLoS ONE 2012, 7, e33032. [CrossRef] [PubMed]
136. Zhang, Y, Wang, J.F, Dong, J, Wei, J.Y, Wang, Y.N, Dai, X.H, Wang, X, Luo, M.J, Tan, W, Deng, X.M, et al. Inhibition of alpha-toxin production by subinhibitory concentrations of naringenin controls Staphylococcus aureus pneumonia. Fitoterapia 2013, 86, 92-99. [CrossRef] [PubMed]
137. Khodaverdian, V, Pesho, M, Truitt, B, Bollinger, L, Patel, P, Nithianantham, S, Yu, G, Delaney, E, Jankowsky, E, Shoham, M. Discovery of antivirulence agents against methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 2013, 57, 3645-3652. [CrossRef] [PubMed]
138. Sully, E.K, Malachowa, N, Elmore, B.O, Alexander, S.M, Femling, J.K, Gray, B.M, DeLeo, F.R, Otto, M, Cheung, A.L, Edwards, B.S, et al. Selective chemical inhibition of agr quorum sensing in Staphylococcus aureus promotes host defense with minimal impact on resistance. PLoS Pathog. 2014, 10, e1004174. [CrossRef] [PubMed]
139. Daly, S.M, Elmore, B.O, Kavanaugh, J.S, Triplett, K.D, Figueroa, M, Raja, H.A, El-Elimat, T, Crosby, H.A, Femling, J.K, Cech, N.B, et al. Omega-hydroxyemodin limits Staphylococcus aureus quorum sensing-mediated pathogenesis and inflammation. Antimicrob. Agents Chemother. 2015, 59, 2223-2235. [CrossRef] [PubMed]
140. Mansson, M, Nielsen, A, Kjaerulff, L, Gotfredsen, C.H, Wietz, M, Ingmer, H, Gram, L, Larsen, T.O. Inhibition of virulence gene expression in Staphylococcus aureus by novel depsipeptides from a marine photobacterium. Mar. Drugs 2011, 9, 2537-2552. [CrossRef] [PubMed]
141. Nielsen, A, Mansson, M, Bojer, M.S, Gram, L, Larsen, T.O, Novick, R.P, Frees, D, Frokiaer, H, Ingmer, H. Solonamide B inhibits quorum sensing and reduces Staphylococcus aureus mediated killing of human neutrophils. PLoS ONE 2014, 9, e84992. [CrossRef] [PubMed]
142. Nielsen, A, Mansson, M, Wietz, M, Varming, A.N, Phipps, R.K, Larsen, T.O, Gram, L, Ingmer, H. Nigribactin, a novel siderophore from Vibrio nigripulchritudo, modulates Staphylococcus aureus virulence gene expression. Mar. Drugs 2012, 10, 2584-2595. [CrossRef] [PubMed]
143. Kjaerulff, L, Nielsen, A, Mansson, M, Gram, L, Larsen, T.O, Ingmer, H, Gotfredsen, C.H. Identification of four new agr quorum sensing-interfering cyclodepsipeptides from a marine Photobacterium. Mar. Drugs 2013, 11, 5051-5062. [CrossRef] [PubMed]
144. Lee, J.H, Park, J.H, Cho, M.H, Lee, J. Flavone reduces the production of virulence factors, staphyloxanthin and alpha-hemolysin, in Staphylococcus aureus. Curr. Microbiol. 2012, 65, 726-732. [CrossRef] [PubMed]
145. Jenkins, R, Burton, N, Cooper, R. Proteomic and genomic analysis of methicillin-resistant Staphylococcus aureus (MRSA) exposed to manuka honey in vitro demonstrated down-regulation of virulence markers. J. Antimicrob. Chemother. 2014, 69, 603-615. [CrossRef] [PubMed]
146. Arya, R, Ravikumar, R, Santhosh, R.S, Princy, S.A. SarA based novel therapeutic candidate against Staphylococcus aureus associated with vascular graft infections. Front. Microbiol. 2015, 6, 416. [CrossRef] [PubMed]
147. Sifri, C.D, Begun, J, Ausubel, F.M, Calderwood, S.B. Caenorhabditis elegans as a model host for Staphylococcus aureus pathogenesis. Infect. Immun. 2003, 71, 2208-2217. [CrossRef] [PubMed]
148. Wu, K, Conly, J, McClure, J.A, Elsayed, S, Louie, T, Zhang, K. Caenorhabditis elegans as a host model for community-associated methicillin-resistant Staphylococcus aureus. Clin. Microbiol. Infect. 2010, 16, 245-254. [CrossRef] [PubMed]
149. Kong, C, Yehye, W.A, Abd Rahman, N, Tan, M.W, Nathan, S. Discovery of potential anti-infectives against Staphylococcus aureus using a Caenorhabditis elegans infection model. BMC Complement. Altern. Med. 2014, 14, 4. [CrossRef] [PubMed]
150. Moy, T.I, Conery, A.L, Larkins-Ford, J, Wu, G, Mazitschek, R, Casadei, G, Lewis, K, Carpenter, A.E, Ausubel, F.M. High-throughput screen for novel antimicrobials using a whole animal infection model. ACS Chem. Biol. 2009, 4, 527-533. [CrossRef] [PubMed]
151. Irazoqui, J.E, Urbach, J.M, Ausubel, F.M. Evolution of host innate defence: Insights from Caenorhabditis elegans and primitive invertebrates. Nat. Rev. Immunol. 2010, 10, 47-58. [CrossRef] [PubMed]
152. Barczak, A.K, Hung, D.T. Productive steps toward an antimicrobial targeting virulence. Curr. Opin. Microbiol. 2009, 12, 490-496. [CrossRef] [PubMed]