Department of Chemistry and Biochemistry, Montana State University, Bozeman, MT 59717, USA.
Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT 59717, USA.
Int J Mol Sci. 2024 Sep 2;25(17):9528. doi: 10.3390/ijms25179528.
The operon encodes a three-protein arsenic resistance system. ArsR regulates the transcription of the operon, while ArsB and ArsC are involved in exporting trivalent arsenic and reducing pentavalent arsenic, respectively. Previous research into 5A has demonstrated that ArsR has regulatory control over a wide range of metal-related proteins and metabolic pathways. We hypothesized that ArsR has broad regulatory control in other Gram-negative bacteria and set out to test this. Here, we use differential proteomics to investigate changes caused by the presence of the gene in human microbiome-relevant during arsenite (As) exposure. We show that ArsR has broad-ranging impacts such as the expression of TCA cycle enzymes during As stress. Additionally, we found that the Isc [Fe-S] cluster and molybdenum cofactor assembly proteins are upregulated regardless of the presence of ArsR under these same conditions. An important finding from this differential proteomics analysis was the identification of response mechanisms that were strain-, ArsR-, and arsenic-specific, providing new clarity to this complex regulon. Given the widespread occurrence of the operon, these findings should have broad applicability across microbial genera, including sensitive environments such as the human gastrointestinal tract.
操纵子编码一个三蛋白砷抗性系统。ArsR 调节操纵子的转录，而 ArsB 和 ArsC 分别参与三价砷的外排和五价砷的还原。先前对 5A 的研究表明，ArsR 对广泛的金属相关蛋白和代谢途径具有调节控制作用。我们假设 ArsR 在其他革兰氏阴性菌中具有广泛的调控作用，并着手对此进行测试。在这里，我们使用差异蛋白质组学来研究在亚砷酸盐（As）暴露期间，基因存在于与人类微生物组相关的 时引起的变化。我们表明，ArsR 在砷胁迫期间对 TCA 循环酶的表达具有广泛的影响。此外，我们发现，无论在相同条件下 ArsR 是否存在，ISC [Fe-S] 簇和钼辅因子组装蛋白的表达都上调。这项差异蛋白质组学分析的一个重要发现是确定了与菌株、ArsR 和砷特异性相关的反应机制，为这个复杂的调控子提供了新的认识。鉴于 操纵子的广泛存在，这些发现应该在包括人类胃肠道等敏感环境在内的微生物属中具有广泛的适用性。
