THE MARR REPRESSOR OF THE MULTIPLE ANTIBIOTIC-RESISTANCE (MAR) OPERONIN ESCHERICHIA-COLI - PROTOTYPIC MEMBER OF A FAMILY OF BACTERIAL REGULATORY PROTEINS INVOLVED IN SENSING PHENOLIC-COMPOUNDS

Background: The marR gene of Escherichia coli encodes a repressor of t he marRAB operon, a regulatory locus controlling multiple antibiotic r esistance in this ore:anism. Inactivation of marR results in increased express;ion of marA, which acts at several target genes in the cell l eading to reduced antibiotic accumulation. Exposure of E. coli to sodi um salicylate (SAL) induces marRAB operon transcription and antibiotic resistance. The mechanism by which SAL antagonizes MarR repressor act ivity is unclear. Materials and Methods: Recombinant plasmid libraries were introduced into a reporter strain designed to identify cloned ge nes encoding MarR repressor activity. Computer analysis of sequence da tabases was also used to search for proteins related to MarR. Results: A second E. coli gene, MprA, that exhibits repressor activity was ide ntified. Subsequent database searching revealed a family of 10 protein s from a variety of bacteria that share significant amino acid sequenc e similarity to MarR and MprA. At least four of these proteins are tra nscriptional repressors whose activity is antagonized by SAL or by phe nolic agents structurally related to SAL. Conclusions: The MarR family is identified as a group of regulatory factors whose activity is modu lated in response to environmental signals in the form of phenolic com pounds. Many of these agents are plant derived. Some of the MarR homol ogs appear more likely to control systems expressed in animal hosts, s uggesting that phenolic sensing by bacteria is important in a variety of environments and in the regulation of numerous processes.