Centre for Preventive Medicine, Animal Health Trust, Kentford, Newmarket, Suffolk, United Kingdom.
Infect Immun. 2010 Nov;78(11):4817-27. doi: 10.1128/IAI.00751-10. Epub 2010 Aug 16.
The acquisition of superantigen-encoding genes by Streptococcus pyogenes has been associated with increased morbidity and mortality in humans, and the gain of four superantigens by Streptococcus equi is linked to the evolution of this host-restricted pathogen from an ancestral strain of the opportunistic pathogen Streptococcus equi subsp. zooepidemicus. A recent study determined that the culture supernatants of several S. equi subsp. zooepidemicus strains possessed mitogenic activity but lacked known superantigen-encoding genes. Here, we report the identification and activities of three novel superantigen-encoding genes. The products of szeF, szeN, and szeP share 59%, 49%, and 34% amino acid sequence identity with SPEH, SPEM, and SPEL, respectively. Recombinant SzeF, SzeN, and SzeP stimulated the proliferation of equine peripheral blood mononuclear cells, and tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ) production, in vitro. Although none of these superantigen genes were encoded within functional prophage elements, szeN and szeP were located next to a prophage remnant, suggesting that they were acquired by horizontal transfer. Eighty-one of 165 diverse S. equi subsp. zooepidemicus strains screened, including 7 out of 15 isolates from cases of disease in humans, contained at least one of these new superantigen-encoding genes. The presence of szeN or szeP, but not szeF, was significantly associated with mitogenic activity in the S. equi subsp. zooepidemicus population (P < 0.000001, P < 0.000001, and P = 0.104, respectively). We conclude that horizontal transfer of these novel superantigens from and within the diverse S. equi subsp. zooepidemicus population is likely to have implications for veterinary and human disease.
猪链球菌获得超抗原编码基因与人类发病率和死亡率增加有关，马链球菌获得四个超抗原与这种宿主受限病原体从机会性病原体马链球菌兽疫亚种的祖先株进化有关。最近的一项研究表明，几种马链球菌兽疫亚种菌株的培养上清液具有有丝分裂活性，但缺乏已知的超抗原编码基因。在这里，我们报告了三个新的超抗原编码基因的鉴定和活性。szeF、szeN 和 szeP 的产物分别与 SPEH、SPEM 和 SPEL 具有 59%、49%和 34%的氨基酸序列同一性。重组 SzeF、SzeN 和 SzeP 刺激了马外周血单核细胞的增殖，并在体外产生了肿瘤坏死因子 alpha（TNF-α）和 gamma 干扰素（IFN-γ）。尽管这些超抗原基因都没有被编码在功能性噬菌体元件内，但 szeN 和 szeP 位于一个噬菌体残余物的旁边，表明它们是通过水平转移获得的。在筛选的 165 种不同的马链球菌兽疫亚种中，有 81 种，包括 15 种来自人类疾病的分离株，含有至少一种这些新的超抗原编码基因。szeN 或 szeP 的存在，但不是 szeF 的存在，与马链球菌兽疫亚种群体中的有丝分裂活性显著相关（P<0.000001，P<0.000001 和 P=0.104，分别）。我们得出结论，这些新型超抗原从多样化的马链球菌兽疫亚种中以及在该亚种内的水平转移可能对兽医和人类疾病产生影响。
