Department of Bacteriology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 815-8582, Japan.
Sci Rep. 2023 Mar 27;13(1):4935. doi: 10.1038/s41598-023-32111-8.
Shiga toxin (Stx) is the key virulence factor of Stx-producing Escherichia coli (STEC). All known Stxs (Stx1 and Stx2) are encoded by bacteriophages (Stx phages). Although the genetic diversity of Stx phages has frequently been described, systematic analyses of Stx phages in a single STEC lineage are limited. In this study, focusing on the O26:H11 STEC sequence type 21 (ST21) lineage, where the stx1a gene is highly conserved, we analysed the Stx1a phages in 39 strains representative of the entire ST21 lineage and found a high level of variation in Stx1a phage genomes caused by various mechanisms, including replacement by a different Stx1a phage at the same or different locus. The evolutionary timescale of events changing Stx1a phages in ST21 was also determined. Furthermore, by using an Stx1 quantification system developed in this study, we found notable variations in the efficiency of Stx1 production upon prophage induction, which sharply contrasted with the conserved iron regulated Stx1 production. These variations were associated with the Stx1a phage alteration in some cases but not in other cases; thus, Stx1 production in this STEC lineage was determined by differences not only in Stx1 phages but also in host-encoded factors.
志贺毒素（Stx）是产志贺毒素大肠杆菌（STEC）的关键毒力因子。所有已知的 Stx（Stx1 和 Stx2）都由噬菌体（Stx 噬菌体）编码。尽管 Stx 噬菌体的遗传多样性经常被描述，但对单个 STEC 谱系中的 Stx 噬菌体进行系统分析是有限的。在这项研究中，我们专注于 O26:H11 STEC 序列型 21（ST21）谱系，其中 stx1a 基因高度保守，我们分析了 39 株代表整个 ST21 谱系的菌株中的 Stx1a 噬菌体，并发现由于各种机制导致 Stx1a 噬菌体基因组发生了高水平的变异，包括在相同或不同位置被不同的 Stx1a 噬菌体取代。还确定了改变 ST21 中 Stx1a 噬菌体的事件的进化时间尺度。此外，通过使用本研究中开发的 Stx1 定量系统，我们发现，在原噬菌体诱导时，Stx1 产生的效率存在显著差异，这与保守的铁调节 Stx1 产生形成鲜明对比。在某些情况下，这些变化与 Stx1a 噬菌体的改变有关，但在其他情况下则没有；因此，该 STEC 谱系中的 Stx1 产生不仅取决于 Stx1 噬菌体的差异，还取决于宿主编码因子的差异。
