Kwan Brian W, Lord Dana M, Peti Wolfgang, Page Rebecca, Benedik Michael J, Wood Thomas K
Department of Chemical Engineering, Pennsylvania State University, University Park, PA, 16802-4400, USA.
Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI, 02912, USA.
Environ Microbiol. 2015 Sep;17(9):3168-81. doi: 10.1111/1462-2920.12749. Epub 2015 Feb 14.
Toxin/antitoxin (TA) systems are ubiquitous within bacterial genomes, and the mechanisms of many TA systems are well characterized. As such, several roles for TA systems have been proposed, such as phage inhibition, gene regulation and persister cell formation. However, the significance of these roles is nebulous due to the subtle influence from individual TA systems. For example, a single TA system has only a minor contribution to persister cell formation. Hence, there is a lack of defining physiological roles for individual TA systems. In this study, phenotype assays were used to determine that the MqsR/MqsA type II TA system of Escherichia coli is important for cell growth and tolerance during stress from the bile salt deoxycholate. Using transcriptomics and purified MqsR, we determined that endoribonuclease toxin MqsR degrades YgiS mRNA, which encodes a periplasmic protein that promotes deoxycholate uptake and reduces tolerance to deoxycholate exposure. The importance of reducing YgiS mRNA by MqsR is evidenced by improved growth, reduced cell death and reduced membrane damage when cells without ygiS are stressed with deoxycholate. Therefore, we propose that MqsR/MqsA is physiologically important for E. coli to thrive in the gallbladder and upper intestinal tract, where high bile concentrations are prominent.
毒素/抗毒素（TA）系统广泛存在于细菌基因组中，许多TA系统的机制已得到充分表征。因此，人们提出了TA系统的几种作用，如噬菌体抑制、基因调控和持久性细胞形成。然而，由于单个TA系统的影响较为微妙，这些作用的重要性尚不清楚。例如，单个TA系统对持久性细胞形成的贡献很小。因此，缺乏对单个TA系统明确的生理作用的定义。在本研究中，通过表型分析确定大肠杆菌的MqsR/MqsA II型TA系统在胆盐脱氧胆酸盐应激期间对细胞生长和耐受性很重要。利用转录组学和纯化的MqsR，我们确定内切核糖核酸酶毒素MqsR降解YgiS mRNA，YgiS mRNA编码一种促进脱氧胆酸盐摄取并降低对脱氧胆酸盐暴露耐受性的周质蛋白。当没有ygiS的细胞受到脱氧胆酸盐应激时，生长改善、细胞死亡减少和膜损伤减少证明了MqsR减少YgiS mRNA的重要性。因此，我们认为MqsR/MqsA对大肠杆菌在胆囊和上肠道中茁壮成长具有重要的生理意义，在这些部位高胆汁浓度很突出。
