The Importance of S. aureus Superantigens in Human Diseases Staphylococcus aureus superantigens in human diseases
Main Article Content
Abstract
Objective: Staphylococcus aureus is a common and important cause of a myriad of serious human infections. The organisms superantigens toxins are causes of many of these diseases. This review discusses the physicochemical and biological properties of superantigens, their roles in human diseases, assays for antibodies against the superantigens, and assays for the superantigen proteins and DNA.
Results: Staphylococcal superantigens include toxic shock syndrome toxin-1, staphylococcal enterotoxin serotypes A to E and G, and staphylococcal superantigen-like serotypes I and K to X. The first human cells staphylococcal superantigens interact with are epithelial cells through the immune co-stimulatory molecule, CD40, and keratinocytes through CD40 and gp130. After penetration into the circulation, superantigens are potent pyrogens, they amplify the lethal effects of Gram-negative endotoxin, and they cause massive T lymphocyte proliferation and macrophage activation, leading to the classic cytokine storm. The “big three” superantigens, toxic shock syndrome toxin-1 and enterotoxins B and C, are important causes of toxic shock syndrome and necrotizing pneumonia after influenza, and are highly associated with infective endocarditis, atopic dermatitis, diabetes mellitus type 2, bullous pemphigoid, numerous autoimmune diseases, and certain types of cancer. Patients who develop serious infections as a result of sero-susceptibility to superantigens do not develop immunity to the toxins as determined by enzyme-linked immunosorbent assays. Commercially-available intravenous immunoglobulins have high titers of protective antibodies. Superantigens associated with human diseases can be assayed for by combinations of antibody-based assays (in body fluids other than blood, and on skin) and polymerase chain reaction, both for detection and quantification. Quantitative polymerase chain reaction has recently been used to demonstrate superantigen DNA in human urine and blood.
Conclusion: Staphylococcal superantigens are known causes of human diseases. Additionally, the proteins are associated with many other human diseases where they have been conclusively shown to be causative. We know how to determine antibodies against superantigens, and we have assays to detect and quantify the superantigens.
Implications: Our ability to measure antibodies to superantigens and detect and quantify the superantigens in humans have allowed us to show that staphylococcal superantigens are important causes of serious infections. Furthermore, these reagents have allowed us to associate staphylococcal superantigens with many other common infections and conditions. This may lead to studies to vaccinate humans against toxoids of at least the three major superantigens, toxic shock syndrome toxin-1 and enterotoxins B and C.
Keywords:
Staphylococcus aureus, superantigens, toxic shock syndrome, staphylococcal infective endocarditis, staphylococcal pneumonia, atopic dermatitis, diabetes mellitus type 2, bullous pemphigoid
Article Details
How to Cite
SCHLIEVERT, Patrick M..
The Importance of S. aureus Superantigens in Human Diseases.
Medical Research Archives, [S.l.], v. 13, n. 7, july 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6729>. Date accessed: 05 dec. 2025.
doi: https://doi.org/10.18103/mra.v13i7.6729.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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2 McCormick, J. K., Yarwood, J. M. & Schlievert, P. M. Toxic shock syndrome and bacterial superantigens: an update. Annu Rev Microbiol 55, 77-104 (2001).
3 Dinges, M. M., Orwin, P. M. & Schlievert, P. M. Exotoxins of Staphylococcus aureus. Clin Microbiol Rev 13, 16-34 (2000).
4 Schlievert, P. M. & Davis, C. C. Device-associated menstrual toxic shock syndrome. Clin Microbiol Rev 33, e00032-19 (2020).
5 MacDonald, K. L. et al. Toxic shock syndrome. A newly recognized complication of influenza and influenzalike illness. Jama 257, 1053-1058 (1987).
6 Bergdoll, M. S., Sugiyama, H. & Dack, G. M. Staphylococcal enterotoxin. I. Purification. Archives of biochemistry and biophysics 85, 62-69 (1959).
7 Bergdoll, M. S. a. S., P.M. Toxic-shock syndrome toxin. Lancet ii, 691 (1984).
8 Kreiswirth, B. N. et al. The toxic shock syndrome exotoxin structural gene is not detectably transmitted by a prophage. Nature 305, 709-712 (1983).
9 Schlievert, P. M., Shands, K. N., Dan, B. B., Schmid, G. P. & Nishimura, R. D. Identification and characterization of an exotoxin from Staphylococcus aureus associated with toxic-shock syndrome. J Infect Dis 143, 509-516 (1981).
10 Bergdoll, M. S., Crass, B. A., Reiser, R. F., Robbins, R. N. & Davis, J. P. A new staphylococcal enterotoxin, enterotoxin F, associated with toxic-shock-syndrome Staphylococcus aureus isolates. Lancet 1, 1017-1021 (1981).
11 Lee, P. K. et al. Nucleotide sequences and biologic properties of toxic shock syndrome toxin 1 from ovine- and bovine-associated Staphylococcus aureus. J Infect Dis 165, 1056-1063 (1992).
12 Blomster-Hautamaa, D. A., Kreiswirth, B. N., Kornblum, J. S., Novick, R. P. & Schlievert, P. M. The nucleotide and partial amino acid sequence of toxic shock syndrome toxin-1. J Biol Chem 261, 15783-15786 (1986).
13 Prasad, G. S. et al. Structure of toxic shock syndrome toxin 1. Biochemistry 32, 13761-13766 (1993).
14 Acharya, K. R. et al. Structural basis of superantigen action inferred from crystal structure of toxic-shock syndrome toxin-1. Nature 367, 94-97 (1994).
15 Mitchell, D. T., Levitt, D. G., Schlievert, P. M. & Ohlendorf, D. H. Structural evidence for the evolution of pyrogenic toxin superantigens. J Mol Evol 51, 520-531 (2000).
16 Betley, M. J., Lofdahl, S., Kreiswirth, B. N., Bergdoll, M. S. & Novick, R. P. Staphylococcal enterotoxin A gene is associated with a variable genetic element. Proc Natl Acad Sci U S A 81, 5179-5183 (1984).
17 Bayles, K. W. & Iandolo, J. J. Genetic and molecular analyses of the gene encoding staphylococcal enterotoxin D. J Bacteriol 171, 4799-4806 (1989).
18 Lindsay, J. A., Ruzin, A., Ross, H. F., Kurepina, N. & Novick, R. P. The gene for toxic shock toxin is carried by a family of mobile pathogenicity islands in Staphylococcus aureus. Mol Microbiol 29, 527-543 (1998).
19 Yarwood, J. M. et al. Characterization and expression analysis of Staphylococcus aureus pathogenicity island 3. Implications for the evolution of staphylococcal pathogenicity islands. J Biol Chem 277, 13138-13147 (2002).
20 Schlievert, P. M. et al. Pyrogenic toxin superantigen site specificity in toxic shock syndrome and food poisoning in animals. Infect Immun 68, 3630-3634 (2000).
21 Schlievert, P. M., Case, L. C., Strandberg, K. L., Abrams, B. B. & Leung, D. Y. Superantigen profile of Staphylococcus aureus isolates from patients with steroid-resistant atopic dermatitis. Clin Infect Dis 46, 1562-1567 (2008).
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