Ogura Yoshitoshi, Mondal Shakhinur Islam, Islam Md Rakibul, Mako Toshihiro, Arisawa Kokichi, Katsura Keisuke, Ooka Tadasuke, Gotoh Yasuhiro, Murase Kazunori, Ohnishi Makoto, Hayashi Tetsuya
Department of Bacteriology, Faculty of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Division of Microbiology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
Sci Rep. 2015 Nov 16;5:16663. doi: 10.1038/srep16663.
Enterohemorrhagic E. coli (EHEC) causes diarrhea and hemorrhagic colitis with life-threatening complications, such as hemolytic uremic syndrome. Their major virulence factor is Shiga toxin (Stx), which is encoded by bacteriophages. Of the two types of Stx, the production of Stx2, particularly that of Stx2a (a subtype of Stx2), is a major risk factor for severe EHEC infections, but the Stx2 production level is highly variable between strains. Here, we define four major and two minor subtypes of Stx2a-encoding phages according to their replication proteins. The subtypes are correlated with Stx2a titers produced by the host O157 strains, suggesting a critical role of the phage subtype in determining the Stx2a production level. We further show that one of the two subclades in the clade 8, a proposed hyper-virulent lineage of O157, carries the Stx2 phage subtype that confers the highest Stx2 production to the host strain. The presence of this subclade may explain the proposed high virulence potential of clade 8. These results provide novel insights into the variation in virulence among O157 strains and highlight the role of phage variation in determining the production level of the virulence factors that phages encode.
肠出血性大肠杆菌（EHEC）可引发腹泻和出血性结肠炎，并伴有诸如溶血尿毒综合征等危及生命的并发症。其主要毒力因子是志贺毒素（Stx），由噬菌体编码。在两种类型的Stx中，Stx2的产生，尤其是Stx2a（Stx2的一种亚型）的产生，是严重EHEC感染的主要危险因素，但不同菌株之间的Stx2产生水平差异很大。在此，我们根据其复制蛋白定义了编码Stx2a的噬菌体的四个主要亚型和两个次要亚型。这些亚型与宿主O157菌株产生的Stx2a滴度相关，表明噬菌体亚型在决定Stx2a产生水平方面起着关键作用。我们进一步表明，在8型分支（一种假定的O157高毒力谱系）中的两个亚分支之一携带的Stx2噬菌体亚型能赋予宿主菌株最高的Stx2产生量。这个亚分支的存在可能解释了8型分支假定的高毒力潜力。这些结果为O157菌株毒力差异提供了新见解，并突出了噬菌体变异在决定噬菌体编码的毒力因子产生水平方面的作用。
