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Staphylococcus enterotoxin profile of China isolates and the superantigenicity of some novel enterotoxins

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Abstract

The genus of staphylococcus widely distributes in environments and contributes to a variety of animal and human diseases. The enterotoxins (SEs) secreted by this type of pathogen have been the leading cause of bacterial toxic shock syndrome and food poisoning, and thus present a substantial concern to public health. In this study, we analyzed the superantigen profile of 122 staphylococcus strains isolated from diverse sources. When screened for the presence and prevalence of 17 known se or se-like (sel) genes, except selj, all other genes were detected in these isolates. In particular, 95.9% of the isolates harbored at least one se/sel gene. Moreover, 47.5% of them bore at least 5. Remarkably, several non-pathogenic species of animal- and environment-origin were also found to carry multiple se/sels. The most frequent genes detected were tsst (62.3%), sei (54.1%), and seb (46.7%), followed by some sel genes (selo, selu, and selm), which also were present at relatively high frequency (20–30%). The generated data improved understanding of strain-specific differences in enterotoxin expression. The gene products of the latter (selo and selu) were subsequently analyzed for their antigenicity in a mouse model using purified E. coli-based recombinant proteins. The studies revealed a strong activity for SEO in induction of T-lymphocyte proliferation and production of various inflammatory cytokines either in vivo or in vitro. In contrast, SEU exhibited little superantigenic effects. The molecular basis for the difference in antigenicity was analyzed by 3D homology remodeling, which revealed a difference in binding and affinities for MHC-II molecules and TCR Vβ region.

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References

  • Akineden Ö, Annemüller C, Hassan A, Lämmler C, Wolter W, Zschöck M (2001) Toxin genes and other characteristics of Staphylococcus aureus isolates from milk of cows with mastitis. Clin Diagn Lab Immunol 8:959–964

    CAS  PubMed  PubMed Central  Google Scholar 

  • Aydin A, Sudagidan M, Muratoglu K (2011) Prevalence of staphylococcal enterotoxins, toxin genes and genetic-relatedness of foodborne Staphylococcus aureus strains isolated in the Marmara Region of Turkey. Int J Food Microbiol 148:99–106

    Article  CAS  PubMed  Google Scholar 

  • Baker MD, Acharya KR (2004) Superantigens: structure-function relationships. Int J Med Microbiol 293:529–537

    Article  CAS  PubMed  Google Scholar 

  • Balaban N, Rasooly A (2000) Staphylococcal enterotoxins. Int J Food Microbiol 61:1–10

    Article  CAS  PubMed  Google Scholar 

  • Bania J, Dabrowska A, Bystron J, Korzekwa K, Chrzanowska J, Molenda J (2006) Distribution of newly described enterotoxin-like genes in Staphylococcus aureus from food. Int J Food Microbiol 108:36–41

    Article  CAS  PubMed  Google Scholar 

  • Becker K, Friedrich AW, Lubritz G, Weilert M, Peters G, von Eiff C (2003) Prevalence of genes encoding pyrogenic toxin superantigens and exfoliative toxins among strains of Staphylococcus aureus isolated from blood and nasal specimens. J Clin Microbiol 41:1434–1439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bergdoll MS, Robbins RN, Weiss K, Borja CR, Huang Y, Chu FS (1973) The staphylococcal enterotoxins: similarities. Contrib Microbiol Immunol 1:390–396

    CAS  PubMed  Google Scholar 

  • Blaiotta G et al (2004) PCR detection of staphylococcal enterotoxin genes in Staphylococcus spp. strains isolated from meat and dairy products. Evidence for new variants of seG and seI in S. aureus AB-8802. J Appl Microbiol 97:719–730

    Article  CAS  PubMed  Google Scholar 

  • Chen J, Novick RP (2009) Phage-mediated intergeneric transfer of toxin genes. Science 323:139–141

    Article  CAS  PubMed  Google Scholar 

  • Chiang YC, Chang LT, Lin CW, Yang CY, Tsen HY (2006) PCR primers for the detection of staphylococcal enterotoxins K, L, and M and survey of staphylococcal enterotoxin types in Staphylococcus aureus isolates from food poisoning cases in Taiwan. J Food Prot 69:1072–1079

    Article  CAS  PubMed  Google Scholar 

  • Chiang Y-C, Liao W-W, Fan C-M, Pai W-Y, Chiou C-S, Tsen H-Y (2008) PCR detection of staphylococcal enterotoxins (SEs) N, O, P, Q, R, U, and survey of SE types in Staphylococcus aureus isolates from food-poisoning cases in Taiwan. Int J Food Microbiol 121:66–73

    Article  CAS  PubMed  Google Scholar 

  • Dinges MM, Orwin PM, Schlievert PM (2000a) Exotoxins of Staphylococcus aureus. Clin Microbiol Rev 13:16–34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dinges MM, Orwin PM, Schlievert PM (2000b) Exotoxins of Staphylococcus aureus. Clin Microbiol Rev 13:16–34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dupuis A, Hennekinne JA, Garin J, Brun V (2008) Protein Standard Absolute Quantification (PSAQ) for improved investigation of staphylococcal food poisoning outbreaks. Proteomics 8:4633–4636

    Article  CAS  PubMed  Google Scholar 

  • Fijalkowski K et al (2014) Comparative analysis of superantigen genes in Staphylococcus xylosus and Staphylococcus aureus isolates collected from a single mammary quarter of cows with mastitis. J Microbiol 52:366–372

    Article  CAS  PubMed  Google Scholar 

  • Fueyo JM, Mendoza MC, Martín MC (2005) Enterotoxins and toxic shock syndrome toxin in Staphylococcus aureus recovered from human nasal carriers and manually handled foods: epidemiological and genetic findings. Microbes infection 7:187–194

    Article  CAS  PubMed  Google Scholar 

  • Garcia P et al (2004) Coagulase-negative staphylococci: clinical, microbiological and molecular features to predict true bacteraemia. J Med Microbiol 53:67–72. doi:10.1099/jmm.0.04994-0

    Article  CAS  PubMed  Google Scholar 

  • Grumann D et al (2008) Immune cell activation by enterotoxin gene cluster (egc)-encoded and non-egc superantigens from Staphylococcus aureus. J Immunol 181:5054–5061

    Article  CAS  PubMed  Google Scholar 

  • Günther S et al (2007) A novel loop domain in superantigens extends their T cell receptor recognition site. J Mol Biol 371:210–221

    Article  PubMed  PubMed Central  Google Scholar 

  • Hodille E et al. (2016) Staphylococcal enterotoxin O exhibits cell cycle modulating activity. Front Microbiol 7:441

    Article  PubMed  PubMed Central  Google Scholar 

  • Hwang SY et al (2007) Novel multiplex PCR for the detection of the Staphylococcus aureus superantigen and its application to raw meat isolates in Korea. Int J Food Microbiol 117:99–105

    Article  CAS  PubMed  Google Scholar 

  • Jarraud S et al (2001) egc, a highly prevalent operon of enterotoxin gene, forms a putative nursery of superantigens in Staphylococcus aureus. J Immunol 166:669–677

    Article  CAS  PubMed  Google Scholar 

  • Jenkins A et al. (2015) Differential expression and roles of Staphylococcus aureus virulence determinants during colonization and disease. MBio 6:e02272–02214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kappler J et al (1989) V beta-specific stimulation of human T cells by staphylococcal toxins. Science 244:811–813

    Article  CAS  PubMed  Google Scholar 

  • Kérouanton A et al (2007) Characterization of Staphylococcus aureus strains associated with food poisoning outbreaks in France. Int J Food Microbiol 115:369–375

    Article  PubMed  Google Scholar 

  • Khosravi AR, Mahdavi Omran S, Shokri H, Lotfi A, Moosavi Z (2012) Importance of elastase production in development of invasive aspergillosis. J Mycol Med 22:167–172

    Article  CAS  PubMed  Google Scholar 

  • Kloos WE, Bannerman TL (1994) Update on clinical significance of coagulase-negative staphylococci. Clin Microbiol Rev 7:117–140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kotzin BL, Leung DY, Kappler J, Marrack P (1993) Superantigens and their potential role in human disease. Adv Immunol 54:99–166

    Article  CAS  PubMed  Google Scholar 

  • Kuroda M et al (2001) Whole genome sequencing of meticillin-resistant Staphylococcus aureus. The Lancet 357:1225–1240

    Article  CAS  Google Scholar 

  • Langford M, Stanton G, Johnson H (1978) Biological effects of staphylococcal enterotoxin A on human peripheral lymphocytes. Infect Immun 22:62–68

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lawrynowicz-Paciorek M, Kochman M, Piekarska K, Grochowska A, Windyga B (2007) The distribution of enterotoxin and enterotoxin-like genes in Staphylococcus aureus strains isolated from nasal carriers and food samples. Int J Food Microbiol 117:319–323

    Article  CAS  PubMed  Google Scholar 

  • Lay MJ, Wittwer CT (1997) Real-time fluorescence genotyping of factor V Leiden during rapid-cycle PCR. Clin Chem 43:2262–2267

    CAS  PubMed  Google Scholar 

  • Le Loir Y, Baron F, Gautier M (2003) Staphylococcus aureus and food poisoning. Genet Mol Res 2:63–76

    PubMed  Google Scholar 

  • Lee HK et al (2014) Clonal spread of catalase-negative ST5/SCCmec II Staphylococcus aureus carrying the Staphylococcal enterotoxin A (Sea), Staphylococcal Enterotoxin B (Seb), and Toxic Shock Toxin (Tst) Virulence Genes. Ann Clin Lab Sci 44:394–398

    CAS  PubMed  Google Scholar 

  • Li Y et al (2001) Crystal structure of a superantigen bound to the high-affinity, zinc-dependent site on MHC class II. Immunity 14:93–104

    Article  CAS  PubMed  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25:402–408

    Article  CAS  PubMed  Google Scholar 

  • Marrack P, Kappler J (1990) The staphylococcal enterotoxins and their relatives. Science 248:705–711

    Article  CAS  PubMed  Google Scholar 

  • Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63

    Article  CAS  PubMed  Google Scholar 

  • Moza B et al (2006) Long-range cooperative binding effects in a T cell receptor variable domain. Proc Natl Acad Sci 103:9867–9872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moza B et al (2007) Structural basis of T-cell specificity and activation by the bacterial superantigen TSST-1. EMBO J 26:1187–1197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Munson SH, Tremaine MT, Betley MJ, Welch RA (1998) Identification and characterization of staphylococcal enterotoxin types G and I from Staphylococcus aureus. Infect Immun 66:3337–3348

    CAS  PubMed  PubMed Central  Google Scholar 

  • Novick RP (2003) Autoinduction and signal transduction in the regulation of staphylococcal virulence. Mol Microbiol 48:1429–1449

    Article  CAS  PubMed  Google Scholar 

  • Omoe K, Hu DL, Takahashi-Omoe H, Nakane A, Shinagawa K (2005) Comprehensive analysis of classical and newly described staphylococcal superantigenic toxin genes in Staphylococcus aureus isolates. FEMS Microbiol Lett 246:191–198

    Article  CAS  PubMed  Google Scholar 

  • Orwin PM, Leung DY, Donahue HL, Novick RP, Schlievert PM (2001) Biochemical and biological properties of staphylococcal enterotoxin K. Infect Immun 69:360–366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Orwin PM et al (2002) Characterization of a novel staphylococcal enterotoxin-like superantigen, a member of the group V subfamily of pyrogenic toxins. BioChemistry 41:14033–14040

    Article  CAS  PubMed  Google Scholar 

  • Pan YQ, Ding D, Li DX, Chen SQ (2007) Expression and bioactivity analysis of Staphylococcal enterotoxin M and N. Protein Expr Purif 56:286–292

    Article  CAS  PubMed  Google Scholar 

  • Podkowik M et al (2016) Genotype and enterotoxigenicity of Staphylococcus epidermidis isolate from ready to eat meat products. Int J Food Microbiol 229:52–59. doi:10.1016/j.ijfoodmicro.2016.04.013

    Article  PubMed  Google Scholar 

  • Rall VL et al (2008) PCR detection of staphylococcal enterotoxin genes in Staphylococcus aureus strains isolated from raw and pasteurized milk. Vet Microbiol 132:408–413

    Article  CAS  PubMed  Google Scholar 

  • Rall VL et al (2014) Diversity of Staphylococcus species and prevalence of enterotoxin genes isolated from milk of healthy cows and cows with subclinical mastitis. J Dairy Sci 97:829–837

    Article  CAS  PubMed  Google Scholar 

  • Reischl U, Linde H-J, Metz M, Leppmeier B, Lehn N (2000) Rapid identification of methicillin-resistant Staphylococcus aureus and simultaneous species confirmation using real-time fluorescence PCR. J Clin Microbiol 38:2429–2433

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rhoden DL, Miller JM (1995) Four-year prospective study of STAPH-IDENT system and conventional method for reference identification of Staphylococcus, Stomatococcus, and Micrococcus spp. J Clin Microbiol 33:96–98

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rodstrom KE, Elbing K, Lindkvist-Petersson K (2014) Structure of the superantigen staphylococcal enterotoxin B in complex with TCR and peptide-MHC demonstrates absence of TCR-peptide contacts. J Immunol 193:1998–2004

    Article  PubMed  Google Scholar 

  • Rodstrom KE, Regenthal P, Lindkvist-Petersson K (2015) Structure of Staphylococcal enterotoxin E in complex with TCR defines the role of TCR loop positioning in superantigen recognition. PLoS One 10:e0131988

    Article  PubMed  PubMed Central  Google Scholar 

  • Ronson CW, Nixon BT, Ausubel FM (1987) Conserved domains in bacterial regulatory proteins that respond to environmental stimuli. Cell 49:579–581

    Article  CAS  PubMed  Google Scholar 

  • Rosec J, Gigaud O (2002) Staphylococcal enterotoxin genes of classical and new types detected by PCR in France. Int J Food Microbiol 77:61–70

    Article  CAS  PubMed  Google Scholar 

  • Schad E et al (1995) Crystal structure of the superantigen staphylococcal enterotoxin type A. EMBO J 14:3292

    CAS  PubMed  PubMed Central  Google Scholar 

  • Soderquist B et al (1998) Cytokine response to staphylococcal exotoxins in Staphylococcus aureus septicemia. Clin Microbiol Infect 4:366–372

    Article  CAS  PubMed  Google Scholar 

  • Sundberg EJ et al (2002a) Structures of two streptococcal superantigens bound to TCR beta chains reveal diversity in the architecture of T cell signaling complexes. Structure 10:687–699

    Article  CAS  PubMed  Google Scholar 

  • Sundberg EJ, Sawicki MW, Southwood S, Andersen PS, Sette A, Mariuzza RA (2002b) Minor structural changes in a mutated human melanoma antigen correspond to dramatically enhanced stimulation of a CD4 + tumor-infiltrating lymphocyte line. J Mol Biol 319:449–461

    Article  CAS  PubMed  Google Scholar 

  • Swaminathan S, Furey W, Pletcher J, Sax M (1995) Residues defining V beta specificity in staphylococcal enterotoxins. Nat Struct Biol 2:680–686

    Article  CAS  PubMed  Google Scholar 

  • Udo EE, Al-Bustan MA, Jacob LE, Chugh TD (1999) Enterotoxin production by coagulase-negative staphylococci in restaurant workers from Kuwait City may be a potential cause of food poisoning. J Med Microbiol 48:819–823

    Article  CAS  PubMed  Google Scholar 

  • Xue Q, Ying YB, Pan YQ, Li DX, Sun HY, Chen SQ (2006) Expression and bioactivity analysis of staphylococcal enterotoxin C2. Yao Xue Xue Bao 41:406–411

    CAS  PubMed  Google Scholar 

  • Yousefi F et al (2016) Tagging staphylococcal enterotoxin B (SEB) with TGFaL3 for breast cancer therapy. Tumour Biol 37:5305–5316

    Article  CAS  PubMed  Google Scholar 

  • Zeng LJ, Huang JH, Liu Y, Zhuang SW, Xue ZH (2010). Bioactivity of the recombinant staphylococcal enterotoxin Q and its structure relationship analysis. Acta Agriculturae Boreali-Sinica 25:80–84

    Google Scholar 

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 31272540) and the underprop project of Tianjin Science and Technology committee (No. 16YFZCNC00640).

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Authors and Affiliations

  1. School of Life Sciences, Tianjin University, 92 Weijin Road, Nankai District, 300072, Tianjin, China

    Menglu Shen, Yi Li, Linlin Zhang, Songbao Dai, Jiashun Wang, Lei Zhang & Jinhai Huang

  2. Beijing Institute of Animal Science and Veterinary Medicine, 100081, Beijing, China

    Yongqing Li

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  1. Menglu Shen
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  2. Yi Li
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  3. Linlin Zhang
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Correspondence to Jinhai Huang.

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The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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Communicated by Erko Stackebrandt.

M. Shen and Y. Li contributed equally to this work.

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Shen, M., Li, Y., Zhang, L. et al. Staphylococcus enterotoxin profile of China isolates and the superantigenicity of some novel enterotoxins. Arch Microbiol 199, 723–736 (2017). https://doi.org/10.1007/s00203-017-1345-6

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