Nakamura Keiji, Taniguchi Itsuki, Gotoh Yasuhiro, Isobe Junko, Kimata Keiko, Igawa Yukiko, Kitahashi Tomoko, Takahashi Yohei, Nomoto Ryohei, Iwabuchi Kaori, Morimoto Yo, Iyoda Sunao, Hayashi Tetsuya
Department of Bacteriology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Toyama Institute of Health, Imizu, Japan.
Front Microbiol. 2024 Aug 6;15:1453887. doi: 10.3389/fmicb.2024.1453887. eCollection 2024.
Shiga toxin (Stx)-producing (STEC) causes serious gastrointestinal illness, including hemorrhagic colitis and hemolytic uremic syndrome. Two types of Stxs (Stx1 and Stx2) are known and both are encoded by bacteriophages (Stx phages), but the production of Stx2 is known to be a major risk factor for severe STEC infections. The production of Stx2, but not Stx1, is tightly coupled with the induction of Stx phages, and Stx2 production levels vary between STEC strains even within the same serotype. Here, we analyzed the genomic diversity of all Stx phages in 71 strains representing the entire O145:H28 lineage, one of the often highly pathogenic STECs, and the relationship between the variations in Stx phage genomes and the levels of Stx2 production by host strains. Our analysis reveals highly dynamic natures of Stx phages in O145:H28, including the independent acquisition of similar Stx phages by different sublineages, the recent transfer of Stx phage between different sublineages, and the frequent gain and loss of Stx phages in some sublineages. We also show the association of the Stx2 phage types with the Stx2 production levels of host strains: strains carrying short-tailed Stx2 phages exhibited significantly higher Stx2 production levels than those carrying long-tailed Stx2 phages. Detailed analyses of the Stx2 phage genomes revealed that both of short- and long-tailed phages exhibited sequence diversification and they were divided into two groups, respectively, based on the sequence similarity of the phage early region encoding genes responsible for phage induction, short-tailed phages contained early regions clearly different in genetic organization from those in long-tailed phages. Therefore, the variations in the early regions between short-and long-tailed Stx2 phages appeared to be linked to a striking difference in Stx2 production levels in their host strains. These results broaden our understanding of the diversification and dynamism of Stx phages in O145:H28 and the association of Stx2 phage types with the Stx2 production level in this STEC lineage.
产志贺毒素（Stx）的大肠杆菌（STEC）会引发严重的胃肠道疾病，包括出血性结肠炎和溶血性尿毒症综合征。已知有两种类型的Stx（Stx1和Stx2），且二者均由噬菌体（Stx噬菌体）编码，但已知Stx2的产生是严重STEC感染的主要风险因素。Stx2而非Stx1的产生与Stx噬菌体的诱导紧密相关，并且即使在同一血清型内，不同STEC菌株的Stx2产生水平也有所不同。在此，我们分析了代表O145:H28谱系（一种通常具有高致病性的STEC）的71个菌株中所有Stx噬菌体的基因组多样性，以及Stx噬菌体基因组变异与宿主菌株Stx2产生水平之间的关系。我们的分析揭示了O145:H28中Stx噬菌体具有高度动态的特性，包括不同亚谱系独立获得相似的Stx噬菌体、近期Stx噬菌体在不同亚谱系之间的转移，以及某些亚谱系中Stx噬菌体的频繁获得和丢失。我们还展示了Stx2噬菌体类型与宿主菌株Stx2产生水平之间的关联：携带短尾Stx2噬菌体的菌株表现出比携带长尾Stx2噬菌体的菌株显著更高的Stx2产生水平。对Stx2噬菌体基因组的详细分析表明，短尾和长尾噬菌体均表现出序列多样化，并且基于负责噬菌体诱导的噬菌体早期区域编码基因的序列相似性，它们分别被分为两组，短尾噬菌体的早期区域在基因组织上与长尾噬菌体明显不同。因此，短尾和长尾Stx2噬菌体早期区域的变异似乎与它们宿主菌株中Stx2产生水平的显著差异有关。这些结果拓宽了我们对O145:H28中Stx噬菌体的多样性和动态性以及该STEC谱系中Stx2噬菌体类型与Stx2产生水平之间关联的理解。
