Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan.
Graduate School of Veterinary Science, Osaka Metropolitan University, Osaka, Japan.
mBio. 2024 Oct 16;15(10):e0229724. doi: 10.1128/mbio.02297-24. Epub 2024 Sep 9.
We have recently described a clinical isolate of strain JH-1 carrying the genes for cytolethal distending toxin (CDT) in a conjugative plasmid. A mutant of strain JH-1, which lost CDT activity, was still found to retain invasiveness and diarrheagenicity. The strain was subjected to phenotypic and genetic analyses including whole genome sequencing (WGS) to explore the genetic determinants of the observed invasiveness and diarrheagenic properties. Analysis and annotation of WGS data revealed the presence of two distinct type III secretion systems (T3SS) in strain JH-1, one of which was located on the chromosome designated as cT3SS (3,992,833 bp) and the other on a mega-plasmid designated as pT3SS (168,819 bp). Comparative genomic analysis revealed that cT3SS is generally conserved in spp. but pT3SS was limited to a subset of spp., carrying genes. Strain JH-1 was found to invade HeLa cells and induce fluid accumulation with characteristic pathological lesions in rabbit ileal loops. Remarkably, these phenomena were associated with the pT3SS but not cT3SS. The plasmid could be transferred by conjugation from strain JH-1 to other strains of , , and with concomitant transfer of these virulence properties. This is the first report of a functional and mobile T3SS in and its association with invasiveness and diarrheagenicity of this bacterium. These data suggest that and other CDT-producing strains might carry T3SS and exert their diarrheagenic effect by exploiting the T3SS nano-machinery.IMPORTANCEThe precise mechanism of virulence of is unclear, although some strains produce cytolethal distending toxin as a putative virulence factor. We have detected the presence of a type III secretion system (T3SS) for the first time on a plasmid in a strain. Plasmid-mediated T3SS seems to be directly involved in virulence of and may serve as a means of horizontal transfer of T3SS genes. Our results may have implication in understanding the mechanism of emergence of new pathogenic strains of .
我们最近描述了一株临床分离株 JH-1，其携带细胞致死膨胀毒素（CDT）的基因位于一个可接合质粒中。一株失去 CDT 活性的 JH-1 突变株仍被发现具有侵袭性和致腹泻性。该菌株进行了表型和遗传分析，包括全基因组测序（WGS），以探讨观察到的侵袭性和致腹泻性特性的遗传决定因素。WGS 数据分析和注释揭示了 JH-1 中存在两种不同的 III 型分泌系统（T3SS），一种位于染色体上，称为 cT3SS（3992833 bp），另一种位于一个巨型质粒上，称为 pT3SS（168819 bp）。比较基因组分析显示，cT3SS 在 spp.中通常保守，但 pT3SS 仅限于 spp.的一个亚群，携带 T3SS 基因。JH-1 菌株被发现能够侵袭 HeLa 细胞，并在兔回肠环中诱导特征性的病理损伤导致液体积累。值得注意的是，这些现象与 pT3SS 相关，而与 cT3SS 无关。质粒可通过接合从 JH-1 菌株转移到其他 spp.、、和菌株，同时转移这些毒力特性。这是首次报道在 中存在功能性和可移动的 T3SS 及其与该细菌侵袭性和致腹泻性的关联。这些数据表明，和其他产生 CDT 的 菌株可能携带 T3SS，并通过利用 T3SS 纳米机器发挥其致腹泻作用。
重要性：尽管一些菌株产生细胞致死膨胀毒素作为潜在的毒力因子，但 的毒力机制尚不清楚。我们首次在一株 菌株的质粒上检测到 III 型分泌系统（T3SS）的存在。质粒介导的 T3SS 似乎直接参与 的毒力，可能是 T3SS 基因水平转移的一种方式。我们的研究结果可能有助于理解新的致病性 菌株出现的机制。
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