College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China.
Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling 712100, China.
Int J Mol Sci. 2021 Oct 8;22(19):10860. doi: 10.3390/ijms221910860.
The arsenic acid-resistant (ArsR) family transcriptional regulators are widely distributed in microorganisms, including in the facultative intracellular pathogen spp. ArsR proteins are implicated in numerous biological processes. However, the specific roles of ArsR family members in remain obscure. Here, we show that ArsR6 (BSS2_RS07325) is required for survival both under heat, oxidative, and osmotic stress and in a murine infection model in vivo. RNA-seq and ChIP-seq reveal that 34 potential target genes for ArsR6 protein were identified, among which eight genes were up-regulated and 26 genes were down-regulated, including outer membrane protein 25D (Omp25D). ArsR6 autoregulates its own expression to maintain bacterial intracellular Cu/Ni homeostasis to benefit bacterial survival in hostile environments. Moreover, ArsR6 also regulates the production of virulence factor Omp25D, which is important for the survival of under stress conditions. Significantly, Omp25D deletion strain attenuated in a murine infection model in vivo. Altogether, our findings reveal a unique mechanism in which the ArsR family member ArsR6 autoregulates its expression and also modulates Omp25D expression to maintain metal ion homeostasis and virulence in .
砷酸抗性(ArsR)家族转录调节因子广泛分布于微生物中,包括兼性细胞内病原体 spp. ArsR 蛋白参与了许多生物学过程。然而, ArsR 家族成员在 中的具体作用尚不清楚。在这里,我们表明 ArsR6(BSS2_RS07325)是 在热、氧化和渗透胁迫以及体内小鼠感染模型中生存所必需的。RNA-seq 和 ChIP-seq 显示,鉴定出了 ArsR6 蛋白的 34 个潜在靶基因,其中 8 个基因上调,26 个基因下调,包括外膜蛋白 25D(Omp25D)。ArsR6 自身调控其表达以维持细菌细胞内 Cu/Ni 平衡,有利于细菌在恶劣环境中的生存。此外,ArsR6 还调节毒力因子 Omp25D 的产生,这对于 在应激条件下的生存至关重要。重要的是,Omp25D 缺失株在体内小鼠感染模型中减弱。总之,我们的研究结果揭示了一种独特的机制,即 ArsR 家族成员 ArsR6 自身调控其表达,并调节 Omp25D 的表达,以维持金属离子平衡和毒力。