Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan 430072, China.
Int J Mol Sci. 2021 Oct 4;22(19):10741. doi: 10.3390/ijms221910741.
HYS is more virulent than toward but the mechanism underlying virulence is unclear. This study is the first to report that the specific gene cluster / in HYS is involved in the virulence of this strain toward , and there are no reports of GtrA, GtrB and GtrII in any species. The pathogenicity of HYS was evaluated using as a host. Based on the prediction of virulence factors and comparative genomic analysis of HYS, we identified 42 specific virulence genes in HYS. Slow-killing assays of these genes showed that the mutation had the greatest effect on the virulence of HYS, and GtrA, GtrB and GtrII all positively affected HYS virulence. Two critical GtrII residues (Glu and Lys) were identified in HYS. Transmission electron microscopy (TEM) showed that GtrA, GtrB and GtrII were involved in the glucosylation of lipopolysaccharide (LPS) O-antigen in HYS. Furthermore, colony-forming unit (CFU) assays showed that GtrA, GtrB and GtrII significantly enhanced HYS colonization in the gut of , and glucosylation of LPS O-antigen and colonization in the host intestine contributed to the pathogenicity of HYS. In addition, experiments using the worm mutants ZD101, KU4 and KU25 revealed a correlation between HYS virulence and the TIR-1/SEK-1/PMK-1 pathways of the innate immune p38 MAPK pathway in . In conclusion, these results reveal that the specific virulence gene cluster // contributes to the unique pathogenicity of HYS compared with other pathogenic , and that this process also involves innate immunity. These findings significantly increase the available information about GtrA/GtrB/GtrII-based virulence mechanisms in the genus .
HYS 比 更具毒性，但毒性的机制尚不清楚。本研究首次报道了 HYS 中特定的基因簇 // 参与了该菌株对 的毒性，而在任何 物种中都没有报道过 GtrA、GtrB 和 GtrII。我们使用 作为宿主来评估 HYS 的致病性。基于对毒力因子的预测和 HYS 的比较基因组分析，我们在 HYS 中鉴定出了 42 个特定的毒力基因。这些基因的慢杀试验表明， 突变对 HYS 的毒性影响最大，而 GtrA、GtrB 和 GtrII 均正向影响 HYS 的毒性。在 HYS 中确定了两个关键的 GtrII 残基（Glu 和 Lys）。透射电子显微镜（TEM）显示，GtrA、GtrB 和 GtrII 参与了 HYS 中脂多糖（LPS）O-抗原的葡糖基化。此外，集落形成单位（CFU）试验表明，GtrA、GtrB 和 GtrII 显著增强了 HYS 在 的肠道定植，LPS O-抗原的葡糖基化和宿主肠道定植有助于 HYS 的致病性。此外，使用 worm 突变体 ZD101、KU4 和 KU25 的实验表明，HYS 的毒力与 先天免疫 p38 MAPK 途径中的 TIR-1/SEK-1/PMK-1 途径之间存在相关性。总之，这些结果表明，与其他致病性 相比，特定的毒力基因簇 // 有助于 HYS 的独特致病性，而且这一过程还涉及 先天免疫。这些发现显著增加了关于 GtrA/GtrB/GtrII 基毒力机制在属中的可用信息。
