Document Type : Original Article
Authors
- Liquan Yu
- Jian Dai
- Ziyao Fan
- Liang Chen
- Daolong Liu
- Zhijun Wu
- Hunan Sun
- Chunyu Tong
- Yongzhong Yu
- Baifen Song
- Jinzhu Ma
- Yudong Cui
School of Life Science and Biotechnology, Heilongjiang Bayi Agricultural University, Daqing 163319, Heilongjiang, China.
Abstract
Background: Staphylococcus aureus is an opportunistic pathogen responsible for various infections with diverse clinical presentation and severity. The α-hemolysin is a major virulence factor in the pathogenesis of S. aureus infections.
Objective: To produce a chimeric fusion protein for hemolytic detection of the S. aureus isolates and as a component of a multi-antigen vaccine.
Methods: The fused strategy employed a flexible linker to incorporate the possible B cell and T cell determinants into one chimera (HlaD). The humoral and cellular response to the HlaD in mice was assessed to reveal a non-significant difference compared with the full-length α-hemolysin mutant (Hla H35L).
Results: The results of the protective effect, the mimetic lung cell injury, and bacterial clearness demonstrated that the mice vaccinated with the HlaD alleviated the severity of the infection of the S. aureus, and the HlaD could similarly function with Hla H35L.
Conclusion: The chimeric fusion (HlaD) provided a diagnostic antigen for hemolysis of the S. aureus strains and a potential vaccine component.
Keywords
- Daum RS, Spellberg B. Progress toward a Staphylococcus aureus vaccine. Clin Infect Dis. 2012; 54:560–567.
- Bubeck Wardenburg J, Schneewind O. Vaccine protection against Staphylococcus aureus pneumonia. J Exp Med. 2008; 205(2):287–294.
- Moran GJ, Krishnadasan A, Gorwitz RJ, Fosheim GE, McDougal LK, Carey RB, et al. Methicillin-resistant S. aureus infections among patients in the emergency department. N Engl J Med. 2006; 355:666–674.
- Foletti D, Strop P, Shaughnessy L, Hasa-Moreno A, Casas MG, Russell M, et al. Mechanism of action and in vivo efficacy of a human-derived antibody against Staphylococcus aureusα-hemolysin. J Mol Biol. 2013; 425(10):1641–1654.
- Tkaczyk C, Hamilton MM, Datta V, Yang XP, Hilliard JJ, Stephens GL, et al. Staphylococcus aureus alpha toxin suppresses effective innate and adaptive immune responses in a murine dermonecrosis model. PLoS one. 2013; 8:e75103.
- Frank KM, Zhou T, Moreno-Vinasco L, Hollett B, Garcia JG, Bubeck Wardenburg J. Host response signature to Staphylococcus aureus alphahemolysin implicates pulmonary TH17 response. Infect Immun. 2012; 80:2161–3169.
- Wilke GA and Bubeck Wardenburg J. Role of a disintegrin and metalloprotease 10 in Staphylococcus aureus alpha-hemolysin-mediated cellular injury. Proc Natl Acad Sci. 2010; 107:13473–13478.
- Kennedy AD, Bubeck Wardenburg J, Gardner DJ, Long D, Whitney AR, Braughton KR, et al. Targeting of alpha-hemolysin by active or passive immunization decreases severity of USA300 skin infection in a mouse model. J Infect Dis. 2010; 202(7):1050–1058.
- Bubeck Wardenburg J, Bae T, Otto M, Deleo FR, Schneewind O. Poring over pores: alpha hemolysin and Panton-Valentine leukocidin in Staphylococcus aureus pneumonia. Nat Med. 2007; 13:1405–1406.
- Ragle BE, Bubeck Wardenburg J. Anti-alpha-hemolysin monoclonal antibodies mediate protection against Staphylococcus aureus pneumonia. Infect Immun. 2009; 77(7):2712–2718.
- Spaulding AR, Lin YC, Merriman JA, Brosnahan AJ, Peterson ML, Schlievert PM. Immunity to Staphylococcus aureussecreted proteins protects rabbits from serious illnesses. Vaccine.2012; 30(34):5099–5109.
- Huseby MJ, Kruse AC, Digre J, Kohler PL, Vocke JA, Mann EE, et al. Beta toxin catalyzes formation of nucleoprotein matrix in staphylococcal biofilms. Proc Natl Acad Sci. 2010; 107:14407–14412.
- Yu LQ, Wang N, Ma JZ, Tong CY, Song BF, Chi JQ, et al. Improved protective efficacy of a chimeric Staphylococcus aureus vaccine candidate iron-regulated surface determinant B (N126-P361)-target of RNAIII activating protein in mice. Microbiol Immunol. 2013; 57:857–864.
- Marmur J. A procedure for the isolation of deoxyribonucleic acid from micro-organisms. J Mol Biol. 1961; 3:208–218.
- Gouaux E. alpha-Hemolysin from Staphylococcus aureus: an archetype of beta-barrel, channel-forming toxins. J Struct Biol. 1998; 121(2):110–22.
- Adhikari RP, Karauzum H, Sarwar J, Abaandou L, Mahmoudieh M, Boroun AR, et al. Novel structurally designed vaccine for S. aureus α-hemolysin: protection against bacteremia and pneumonia. PLoS One. 2012; 7(6):e38567.
- Redi D, Raffaelli CS, Rossetti B, De Luca A, Montagnani F. Staphylococcus aureus vaccine preclinical and clinical development: current state of the art. New Microbiol. 2018;41(3):208–13.
- Adhikari RP, Karauzum H, Sarwar J, Abaandou L, Mahmoudieh M, Boroun AR, et al. Novel structural designed vaccine for S. aureus α-hemolysin: protection against bactermia and pneumonia. Plos One. 2012; 7(6):e38567.
- Oscherwitz J, Muñoz-Planillo R, Yu F, Núñez G, Cease KB. In vovo mapping of a protective linear neutralizing epitope at the N-terminus of alpha hemolysin from Staphylococcus aureus. Mol Immunol. 2014; 60(1):62–71.
- Foletti D, Strop P, Shaughnessy L, Hasa-Moreno A, Casas MG, Russell M, 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.
- Toshimitsu K and Eric G. Arresting and releasing Staphylococcal α-hemolysin at intermediate stages of pore formation by engineered disulfide bonds. Protein Sci. 2003; 12:997–1006.
- Cua DJ, Tato CM. Innate IL-17-producing cells: The sentinels of the immune system. Nat Rev Immunol. 2010; 10:479–489.
- Hirst RAH, Yesilkaya E, Clitheroe A, Rutman N, Dufty TJ, Mitchell C, et al. Sensitivities of human monocytes and epithelial cells to pneumolysin are different. Infect Immun. 2002; 70:1017–1022.
)