细菌全局性调控因子CsrA的结构与功能

碳存储调控因子A (carbon storage regulator, CsrA) 是一种RNA结合蛋白,在细菌的碳代谢、生物被膜形成、运动性、病原菌毒力、群体感应、环二鸟苷酸信号合成、应激感应等多种生理过程中具有重要调节功能,是全局性调控蛋白.它通过与靶标mRNA的特异结合,抑制其翻译或增强其稳定性来调控下游基因的表达,属于转录后调控因子的范畴.CsrA蛋白的表达与活性受碳存储调控(Csr)系统本身多个自主调节回路的精密控制：　一些小的非编码RNA (snmRNAs,如CsrB/C）作为拮抗因子与CsrA二聚体结合并抑制其活性;而这些snmRNAs在体内又可在CsrD的辅助下被核糖核酸内切酶E和多核苷酸磷酸化酶降解,释放CsrA的活性.当前,对于Csr系统的调节作用、调控通路与机制的研究是细菌学研究的热点,本文综述了该蛋白及Csr系统的结构、功能和作用机制的最新研究进展.     

Biofilm Formation and Dispersal under the Influence of the Global Regulator CsrA of Escherichia coli

The predominant mode of growth of bacteria in the environment is within sessile, matrix-enclosed communities known as biofilms. Biofilms often complicate chronic and difficult-to-treat infections by protecting bacteria from the immune system, decreasing antibiotic efficacy, and dispersing planktonic cells to distant body sites. While the biology of bacterial biofilms has become a major focus of microbial research, the regulatory mechanisms of biofilm development remain poorly defined and those of dispersal are unknown. Here we establish that the RNA binding global regulatory protein CsrA (carbon storage regulator) of Escherichia coli K-12 serves as both a repressor of biofilm formation and an activator of biofilm dispersal under a variety of culture conditions. Ectopic expression of the E. coli K-12 csrA gene repressed biofilm formation by related bacterial pathogens. A csrA knockout mutation enhanced biofilm formation in E. coli strains that were defective for extracellular, surface, or regulatory factors previously implicated in biofilm formation. In contrast, this csrA mutation did not affect biofilm formation by a glgA (glycogen synthase) knockout mutant. Complementation studies with glg genes provided further genetic evidence that the effects of CsrA on biofilm formation are mediated largely through the regulation of intracellular glycogen biosynthesis and catabolism. Finally, the expression of a chromosomally encoded csrA'-'lacZ translational fusion was dynamically regulated during biofilm formation in a pattern consistent with its role as a repressor. We propose that global regulation of central carbon flux by CsrA is an extremely important feature of E. coli biofilm development.