OxyR-activated expression of Dps is important for Vibrio cholerae oxidative stress resistance and pathogenesis.
OxyR-activated expression of Dps is important for Vibrio cholerae oxidative stress resistance and pathogenesis.
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OxyR 激活的 Dps 表达对于霍乱弧菌氧化应激抵抗和发病机制很重要
DOI：
10.1371/journal.pone.0171201
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Zhu J
中科院分区：
文献类型：
--
作者：
Xia X;Larios-Valencia J;Liu Z;Xiang F;Kan B;Wang H;Zhu J
霍乱弧菌是霍乱（一种脱水性腹泻病）的病原体。这种革兰氏阴性病原体能够调节其基因表达，以对抗水生环境和宿主环境中遇到的压力，包括活性氧 (ROS) 造成的压力。为了进一步了解霍乱弧菌对 ROS 的转录反应，我们进行了 RNA 测序分析，以确定霍乱弧菌暴露于氢过氧化氢时的转录谱。在 135 个差异表达基因中，VC0139 是诱导量最大的基因之一。 VC0139 编码与 DPS（来自饥饿细胞的 DNA 结合蛋白）蛋白家族同源的蛋白，该蛋白家族广泛保守，并与其他细菌的 ROS 抗性有关。使用启动子报告基因检测，我们发现在指数生长过程中，dps 是由 H2O2 诱导的，其方式依赖于 ROS 感应转录调节因子 OxyR。进入稳定期后，需要主要的稳定期调节器 RpoS 来转录 dps。 dps 的缺失削弱了霍乱弧菌对无机和有机氢过氧化物的抵抗力。此外，我们表明 Dps 参与抵抗多种环境压力。最后，我们发现 Dps 对于霍乱弧菌成年小鼠的定植很重要，但在抗氧化剂存在的情况下就变得可有可无。综上所述，我们的结果表明 Dps 在霍乱弧菌应激抵抗和发病机制中发挥着至关重要的作用。
Vibrio cholerae is the causative agent of cholera, a dehydrating diarrheal disease. This Gram-negative pathogen is able to modulate its gene expression in order to combat stresses encountered in both aquatic and host environments, including stress posed by reactive oxygen species (ROS). In order to further the understanding of V. cholerae’s transcriptional response to ROS, we performed an RNA sequencing analysis to determine the transcriptional profile of V. cholerae when exposed to hydrogen hydroperoxide. Of 135 differentially expressed genes, VC0139 was amongst the genes with the largest induction. VC0139 encodes a protein homologous to the DPS (DNA-binding protein from starved cells) protein family, which are widely conserved and are implicated in ROS resistance in other bacteria. Using a promoter reporter assay, we show that during exponential growth, dps is induced by H2O2 in a manner dependent on the ROS-sensing transcriptional regulator, OxyR. Upon entry into stationary phase, the major stationary phase regulator RpoS is required to transcribe dps. Deletion of dps impaired V. cholerae resistance to both inorganic and organic hydroperoxides. Furthermore, we show that Dps is involved in resistance to multiple environmental stresses. Finally, we found that Dps is important for V. cholerae adult mouse colonization, but becomes dispensable in the presence of antioxidants. Taken together, our results suggest that Dps plays vital roles in both V. cholerae stress resistance and pathogenesis.