Iron-Sulfur Cluster Repair Contributes to Yersinia pseudotuberculosis Survival within Deep Tissues
Iron-Sulfur Cluster Repair Contributes to Yersinia pseudotuberculosis Survival within Deep Tissues
复制标题
DOI：
10.1128/iai.00533-19
复制
发表时间：
2019-10-01
影响因子：
3.1
通讯作者：
Isberg, Ralph R.
中科院分区：
文献类型：
--
作者：
Davis, Kimberly M.;Krupp, Joanna;Isberg, Ralph R.
为了成功地定殖宿主组织，细菌必须对许多不同的宿主衍生的抗微生物化合物（如一氧化氮（NO））作出反应并解毒。NO通过攻击含铁-硫（Fe-S）簇的蛋白质而具有直接的抗微生物活性。NO解毒在促进细菌存活中起着重要作用，但目前尚不清楚Fe-S簇的修复是否对宿主组织内的细菌存活也很重要。在这里，我们表明，铁硫簇修复蛋白YtfE有助于生存的假结核耶尔森氏菌在脾脏亚硝化应激。Y.假结核病在深部组织内形成复制细菌的聚集中心，其中外周细菌表达NO解毒基因hmp。ytfE表达也特异性地发生在小菌落边缘的外周细胞内。在不存在ytfE的情况下，小菌落的面积显著小于野生型（WT）的小菌落的面积，这与ytfE有助于外周细胞的存活一致。ytfE的损失没有改变细胞解毒NO的能力，这发生在WT和Δ ytfE小菌落的外周细胞内。在没有NO解毒活性的hmp，NO扩散在三角洲ytfE小菌落，并有一个显着减少的面积缺乏ytfE的小菌落，表明ytfE也有助于细菌的生存在没有NO解毒。这些结果表明Fe-S簇修复在Y.脾内的假结核，并表明细胞外细菌可能依赖于这一途径在宿主组织内生存。
To successfully colonize host tissues, bacteria must respond to and detoxify many different host-derived antimicrobial compounds, such as nitric oxide (NO). NO has direct antimicrobial activity through attack on iron-sulfur (Fe-S) cluster-containing proteins. NO detoxification plays an important role in promoting bacterial survival, but it remains unclear if repair of Fe-S clusters is also important for bacterial survival within host tissues. Here we show that the Fe-S cluster repair protein YtfE contributes to the survival of Yersinia pseudotuberculosis within the spleen following nitrosative stress. Y. pseudotuberculosis forms clustered centers of replicating bacteria within deep tissues, where peripheral bacteria express the NO-detoxifying gene hmp. ytfE expression also occurred specifically within peripheral cells at the edges of microcolonies. In the absence of ytfE, the area of microcolonies was significantly smaller than that of the wild type (WT), consistent with ytfE contributing to the survival of peripheral cells. The loss of ytfE did not alter the ability of cells to detoxify NO, which occurred within peripheral cells in both WT and Delta ytfE microcolonies. In the absence of NO-detoxifying activity by hmp, NO diffused across Delta ytfE microcolonies, and there was a significant decrease in the area of microcolonies lacking ytfE, indicating that ytfE also contributes to bacterial survival in the absence of NO detoxification. These results indicate a role for Fe-S cluster repair in the survival of Y. pseudotuberculosis within the spleen and suggest that extracellular bacteria may rely on this pathway for survival within host tissues.