Kobayashi Yohei, Suzuki Masato, Umeda Shuntaro, Oka Keisuke, Takahashi Kenichi, Shibayama Keigo, Shibata Shinichiro
Department of Microbiology, Nagoya City Public Health Research Institute, Nagoya, Japan.
Department of Bacteriology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Microbiol Spectr. 2025 Aug 5;13(8):e0017525. doi: 10.1128/spectrum.00175-25. Epub 2025 Jun 24.
Non-O1/non-O139 (NOVC) causes sporadic intestinal infections and systemic symptoms. Recently, global warming has led to an increase in NOVC infections; however, there have been no reports on the genomic analysis of clinical NOVC isolates in Japan, and the molecular understanding of NOVC remains inadequate. We identified three cases of NOVC infection in Nagoya, Japan, in 2020 and performed genomic analysis to reveal the molecular characteristics of these isolates and compared them with those of previously reported clinical cases. Phylogenetic analysis revealed high diversity. This result indicates that the three cases were sporadic within the area over a short period of time from multiple contaminated sources. However, most clinical isolates carried virulence factor genes encoding El Tor type hemolysin, type VI secretion system (T6SS), and repeats-in-toxin toxin, and approximately half of the isolates carried encoded on VPI-2, as well as the type III secretion system (T3SS). Additionally, detailed whole-genome sequencing (WGS) analysis revealed various types of T3SS, T6SS, VPI-2, and VSP-2. Variations in the number of Rep1 units of VopM were observed in the T3SS of the NOVC isolates in this study. The T6SS type identified in this study consisted of a large cluster and auxiliary clusters, showing diversity among the NOVC isolates. We recommend continued monitoring of clinical NOVC isolates as horizontal transmission along with host and environmental recombination may lead to changes in virulence.IMPORTANCEAlthough reports of non-O1/non-O139 (NOVC) infections are rare, their actual incidence remains uncertain. This is partly due to nonspecific symptoms, the absence of a surveillance system in most countries including Japan, and the lack of appropriate laboratory culture techniques. However, NOVCs in the environment are increasing due to global warming, and the risk of NOVC infections is increasing. In this study, we conducted a comprehensive genomic analysis of clinical NOVC isolates from a city in Japan and compared their virulence factor profiles with those of previously reported clinical isolates using whole-genome sequencing (WGS). This result indicates that some sporadic cases have occurred in the area, suggesting that there are multiple sources of NOVC infection. The accumulation of such data will enhance our understanding of the pathogenicity of NOVCs and improve diagnostic accuracy.
非O1/非O139(NOVC)可引起散发性肠道感染和全身症状。最近,全球变暖导致NOVC感染增加;然而,日本尚无关于临床NOVC分离株基因组分析的报道,对NOVC的分子认识仍然不足。我们在2020年于日本名古屋发现了3例NOVC感染病例,并进行了基因组分析以揭示这些分离株的分子特征,并将它们与先前报道的临床病例的特征进行比较。系统发育分析显示出高度的多样性。这一结果表明,这3例病例在短时间内是该地区来自多个污染源的散发病例。然而,大多数临床分离株携带编码埃尔托型溶血素、VI型分泌系统(T6SS)和毒素重复序列的毒力因子基因,约一半的分离株携带VPI-2上编码的基因以及III型分泌系统(T3SS)。此外,详细的全基因组测序(WGS)分析揭示了各种类型的T3SS、T6SS、VPI-2和VSP-2。在本研究的NOVC分离株的T3SS中观察到VopM的Rep1单位数量存在差异。本研究中鉴定的T6SS类型由一个大簇和辅助簇组成,显示出NOVC分离株之间的多样性。我们建议持续监测临床NOVC分离株,因为水平传播以及宿主和环境重组可能导致毒力变化。重要性虽然非O1/非O139(NOVC)感染的报告很少,但其实际发病率仍不确定。部分原因是症状不具特异性、包括日本在内的大多数国家缺乏监测系统以及缺乏适当的实验室培养技术。然而,由于全球变暖,环境中的NOVC正在增加,NOVC感染的风险也在增加。在本研究中,我们对来自日本一个城市的临床NOVC分离株进行了全面的基因组分析,并使用全基因组测序(WGS)将它们的毒力因子谱与先前报道的临床分离株的毒力因子谱进行比较。这一结果表明该地区发生了一些散发病例,提示存在多个NOVC感染源。积累此类数据将增强我们对NOVC致病性的理解并提高诊断准确性。