Sulavik M C, Gambino L F, Miller P F
Therapeutics Department, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105, USA.
Mol Med. 1995 May;1(4):436-46.
The marR gene of Escherichia coli encodes a repressor of the marRAB operon, a regulatory locus controlling multiple antibiotic resistance in this organism. Inactivation of marR results in increased expression of marA, which acts at several target genes in the cell leading to reduced antibiotic accumulation. Exposure of E. coli to sodium salicylate (SAL) induces marRAB operon transcription and antibiotic resistance. The mechanism by which SAL antagonizes MarR repressor activity is unclear.
Recombinant plasmid libraries were introduced into a reporter strain designed to identify cloned genes encoding MarR repressor activity. Computer analysis of sequence databases was also used to search for proteins related to MarR.
A second E. coli gene, MprA, that exhibits MarR repressor activity was identified. Subsequent database searching revealed a family of 10 proteins from a variety of bacteria that share significant amino acid sequence similarity to MarR and MprA. At least four of these proteins are transcriptional repressors whose activity is antagonized by SAL or by phenolic agents structurally related to SAL.
The MarR family is identified as a group of regulatory factors whose activity is modulated in response to environmental signals in the form of phenolic compounds. Many of these agents are plant derived. Some of the MarR homologs appear more likely to control systems expressed in animal hosts, suggesting that phenolic sensing by bacteria is important in a variety of environments and in the regulation of numerous processes.
大肠杆菌的marR基因编码marRAB操纵子的阻遏蛋白,该调控位点控制着该生物体中的多种抗生素抗性。marR的失活导致marA表达增加,marA作用于细胞中的多个靶基因,导致抗生素积累减少。将大肠杆菌暴露于水杨酸钠(SAL)会诱导marRAB操纵子转录和抗生素抗性。SAL拮抗MarR阻遏蛋白活性的机制尚不清楚。
将重组质粒文库导入一个报告菌株,该菌株用于鉴定编码MarR阻遏蛋白活性的克隆基因。还利用序列数据库的计算机分析来搜索与MarR相关的蛋白质。
鉴定出了第二个具有MarR阻遏蛋白活性的大肠杆菌基因MprA。随后的数据库搜索揭示了一个由来自多种细菌的10种蛋白质组成的家族,它们与MarR和MprA具有显著的氨基酸序列相似性。这些蛋白质中至少有四种是转录阻遏蛋白,其活性受到SAL或与SAL结构相关的酚类试剂的拮抗。
MarR家族被鉴定为一组调控因子,其活性会响应酚类化合物形式的环境信号而受到调节。这些试剂中的许多是植物来源的。一些MarR同源物似乎更有可能控制在动物宿主中表达的系统,这表明细菌对酚类的感知在多种环境和众多过程的调节中很重要。