The marA gene encodes a transcriptional activator that autoactivates expression of the marRAB operon and that regulates the expression of a global network of at least 80 chromosomal genes [14, 15, 16, 17]. Under laboratory conditions, the marRAB operon can be induced by tetracycline, chloramphenicol, or salicylate [1, 4, 18, 19, 20], plumbagin, dinitrophenol, and menadione [21], and other chemicals with phenolic rings [21]. All these compounds attenuate the ability of MarR homodimers to bind their cognate DNA sequences [22]. Cross talk between the mar and rob systems plays an important role in the response to salicylate [23]. Based on the crystal structure, it was reported that there are two possible salicylate sites, SAL-A and SAL-B, in MarR [17]. However, these are not the physiological regulatory sites [24]. On the other hand, based on mutational analysis of the MarR homologue MTH313 from Methanobacterium thermautotrophicum, residues P57, R86, M74, and R77 were found important for DNA binding; residues R16, D26, and K44 significantly reduced binding to either salicylate or 2,4-dinitrophenol, and residue H19 impaired the binding to 2,4-dinitrophenol. These findings indicate, as with MTH313, the presence of a ligand-binding pocket located between the dimerization and DNA-binding domains [24]. For inactivation of MarR by salicylate, 2-4-dinitrophenol, or plumbagin, most of the residues important for ligand effectiveness lie in the α1 and α2 helices of MarR, between the putative DNA-binding domain and the dimerization domain of MarR [25]. 2,3-Dihydroxybenzoate (DHB), anthranilate, and 4-hydroxybenzoate (in the absence of TolC), which are involved in enterobactin, tryptophan, and ubiquinone biosynthesis, respectively, can activate marRAB transcription. However, only DHB directly binds to MarR, affecting its activity [26]. More studies to determine whether DHB is the MarR effector under physiological conditions are needed [26]. Sulfane sulfur is also sensed by MarR; in its presence the formation of a disulfide bond between Cys-80 residues in MarR is induced, causing tetramerization of MarR, a form which has a decreased affinity to its DNA []. Based on footprinting experiments and crystal structure analysis, MarR binds as a dimer to two direct repeat elements in the mar operator (marO) [2, 4, 17, 27]. Each dimer subunit consists of six helical regions and a winged helix DNA-binding motif [17], organized in such a way that the terminal parts of each monomer contribute to an extensive protein-protein interface in the dimer. Both direct repeat elements are required for full transcriptional repression, but either site alone permits partial repression [3]. N-terminal and central regions of MarR are responsible for the specific interactions with the two binding sites in marO [14], and the C-terminal domain is also necessary for proper repressor function [5, 28]. Biochemical and crystal structure analyses have demonstrated that the N- and C-terminal regions of MarR contribute to dimer formation [5]. Two conformational states generated by helix-loop-helix motifs of MarR [mediated by copper(II) oxidation of its Cys80] are important for its binding to and stabilization with DNA [29]. The MarR regulator from Escherichia coli belongs to the MarR family, and it has two helix-turn-helix domains involved mainly in the development of antibiotic resistance [30, 31]. The marR-type helix-turn-helix domain is well distributed among eubacteria and archaea, with at least 10 proteins from a variety of bacteria [17]. MarR plays an important role in the control of biological functions, including resistance to multiple antibiotics, organic solvents, household disinfectants, and oxidative stress agents. It also regulates synthesis of the virulence factor in pathogens of humans and plants, and it also responds to aromatic compounds [12, 17, 32, 33]. The DNA-binding domains of MarR adopt a conserved winged helix (or winged helix-turn-helix) fold [22]. Homologs of MarR are found in both bacterial and archaeal domains. The MarR family is one of nine families of transcription factors that evolved before divergence of these domains, over 3 billion years ago [34, 35]. The Mar locus in Escherichia coli consists of two divergently transcribed operons, marC and marRAB, which control an adaptation response to antibiotics and other environmental hazards [14]. Organic solvent tolerance levels are greatly increased in double mutants of the proV and marR genes [36]. An increase of organic solvent tolerances (OSTs) was shown by using the fadR and marR double mutant of those two transcriptional regulators [37]. marR shows differential codon adaptation, resulting in differential translation efficiency signatures, in thermophilic microbes. It was therefore predicted to play a role in the heat shock response. A marR deletion mutant was shown to be more sensitive than the wild type, specifically to heat shock, but not other stresses [38]. An ultrasensitive surface-enhanced Raman scatering (SERS) assay was developed to detect Cu²⁺ using the MarR transcription factor, which is a potentially universal Cu²⁺-specific biorecognition element [39]. The effects of a mutation that inactivated MarR, caused a decrease in growth fitness, and enhanced the resistance to ciprofloxacin was reverted by mutations in marA or lon genes, as the growth fitness was enhanced and the antibiotic resistance was decreased [40]. Review: [41] Please note that results reported in [42] were later found to be erroneous; see the corrigendum published in Molecular Microbiology, 80 (2011): 853. doi: 10.1111/j.1365-2958.2011.07642.x, and the subsequent retraction [43]. [44] has been retracted [45].