大肠杆菌抗酸碱环境的分子机制

细胞抗酸碱机制是一个重要的分子生物学问题，也是当前国际上非常活跃的研究前沿领域。大肠杆菌的抗酸系统中，与代谢相关的抗酸机制是利用氨基酸脱羧酶消耗氨基酸特定的氢离子，产生胺类和CO2，最终提高pH值。周质空间的抗酸机制，主要是依靠分子伴侣来保护周质空间中蛋白质。细菌二元调控系统可以感知极端pH环境等外界刺激，激活或抑制靶基因的表达，使细胞做出应答。非编码小RNA的抗酸途径则通过增加RpoS或者降低H NS的翻译来实现。关于大肠杆菌抗碱机制的研究甚少，至今只发现gadC、rpoS、nhaA和tnaA四个基因可能帮助大肠杆菌细胞耐受极碱环境。揭示大肠杆菌抗酸碱途径的生物学机制，对人肠道致病菌的治疗和预防都有着积极的作用，也能为生物医药的研究提供可靠的分子依据和新药开发的新靶点。

The Molecular Mechanism of Sensing and Adapting to Acid and Base Stress in E.coli

The study of acid and base stress responses is an emerging frontier in modern molecular biology. There are three major mechanisms for the acid stress response in E.coli. First, The metabolism associated acid response system, consisting of four amino acid decarboxylases that catalyze proton-dependent decarboxylation of a substrate amino acid to product amines and CO2, as well as to increase the pH value. Second, acid resistance in the periplasmic space relies mainly on molecular chaperones to protect proteins in the periplasmic space. Third, the bacterial two component system. It senses external stimuli such as extreme pH, and thereby activates or inhibits the expression of target genes so that cells could respond accordingly. Recently, noncoding small RNAs have also been identified to play a role, by increasing RpoS translation or blocking H NS translation. As to alkaline resistance, few studies have been done, and only four genes, gadC, rpoS, nhaA and tnaA have been found to assist E.coli to tolerate an alkaline environment. Studies to reveal the mechanisms of acid and base stress responses in E.coli will not only benefit the treatment and prevention of pathogenic entero bacteria, but also provide a reliable molecular basis and a new target for the development of biological medicine.