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MarR DNA-binding transcriptional repressor

Synonyms: MarR-2,4-dinitrophenol, MarR-Benzoate, MarR-Menadione, MarR-Paraquat, MarR-Phenazine methosulfate, MarR-Plumbagin, MarR-Sodium salicylate, MarR, MarR-salicylate
Summary:
MarR, "Multiple antibiotic resistance" [2], participates in controlling several genes involved in resistance to antibiotics [7], multidrug efflux [8, 9, 10], oxidative stress [11], organic solvents [12], and heavy metals [11]. The antibiotic resistance associated with MarR appears to involve the acidification of the cytoplasm [7]. MarR is part of the marRAB operon and negatively autoregulates its own expression [13].
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
MarR Functional   Apo [BPP], [GEA] [1]
MarR-2,4-dinitrophenol Non-Functional Allosteric Holo [BPP], [GEA] [1]
MarR-Benzoate Non-Functional Allosteric Holo [BPP], [GEA] [1]
MarR-Menadione Non-Functional Allosteric Holo [BPP], [GEA] [1]
MarR-Paraquat Non-Functional Allosteric Holo [BPP], [GEA] [1]
MarR-Phenazine methosulfate Non-Functional Allosteric Holo [BPP], [GEA] [1]
MarR-Plumbagin Non-Functional Allosteric Holo [BPP], [GEA] [1]
MarR-Sodium salicylate Non-Functional Allosteric Holo nd nd
MarR-salicylate Non-Functional Allosteric Holo [BPP], [GEA] [1]
Evolutionary Family: MarR
Connectivity class: Local Regulator
Gene name: marR
  Genome position: 1619120-1619554
  Length: 435 bp / 144 aa
Operon name: marRAB
TU(s) encoding the TF:
Transcription unit        Promoter
marRAB
marRp


Regulon       
Regulated gene(s) marA, marB, marR
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
drug resistance/sensitivity (3)
Transcription related (2)
repressor (2)
operon (2)
detoxification (2)
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Regulated operon(s) marRAB
First gene in the operon(s) marR
Simple and complex regulons AcrR,CRP,CpxR,Cra,Fis,MarA,MarR,Rob,SoxS
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[MarR,-](1)


Transcription factor regulation    


Transcription factor binding sites (TFBSs) arrangements
      

  Functional conformation Function Promoter Sigma factor Central Rel-Pos Distance to first Gene Genes Sequence LeftPos RightPos Evidence (Confirmed, Strong, Weak) References
  MarR repressor marRp Sigma70 -18.0 -45.0 marR, marA, marB
catttgacttATACTTGCCTGGGCAATATTATcccctgcaac
1619064 1619085 [GEA], [AIBSCS], [APIORCISFBSCS], [BPP], [GS], [SM] [1], [2], [3], [4], [5], [6]
  MarR repressor marRp Sigma70 17.0 -11.0 marR, marA, marB
cctgcaactaATTACTTGCCAGGGCAACTAATgtgaaaagta
1619098 1619119 [GEA], [AIBSCS], [APIORCISFBSCS], [BPP], [GS], [SM] [1], [2], [3], [4], [5], [6]


Evolutionary conservation of regulatory elements    
     Note: Evolutionary conservation of regulatory interactions and promoters is limited to gammaproteobacteria.
Promoter-target gene evolutionary conservation




Reference(s)    

 [1] Seoane AS., Levy SB., 1995, Characterization of MarR, the repressor of the multiple antibiotic resistance (mar) operon in Escherichia coli., J Bacteriol 177(12):3414-9

 [2] Cohen SP., Hachler H., Levy SB., 1993, Genetic and functional analysis of the multiple antibiotic resistance (mar) locus in Escherichia coli., J Bacteriol 175(5):1484-92

 [3] Martin RG., Rosner JL., 2004, Transcriptional and translational regulation of the marRAB multiple antibiotic resistance operon in Escherichia coli., Mol Microbiol 53(1):183-91

 [4] Martin RG., Rosner JL., 1995, Binding of purified multiple antibiotic-resistance repressor protein (MarR) to mar operator sequences., Proc Natl Acad Sci U S A 92(12):5456-60

 [5] Notka F., Linde HJ., Dankesreiter A., Niller HH., Lehn N., 2002, A C-terminal 18 amino acid deletion in MarR in a clinical isolate of Escherichia coli reduces MarR binding properties and increases the MIC of ciprofloxacin., J Antimicrob Chemother 49(1):41-7

 [6] Shimada T., Ogasawara H., Ishihama A., 2018, Single-target regulators form a minor group of transcription factors in Escherichia coli K-12., Nucleic Acids Res 46(8):3921-3936

 [7] Reyes-Fernández EZ, Schuldiner S, 2020, Acidification of Cytoplasm in Escherichia coli Provides a Strategy to Cope with Stress and Facilitates Development of Antibiotic Resistance., Sci Rep, 10(1):9954 10.1038/s41598-020-66890-1

 [8] Ruiz C., Levy SB., 2010, Many chromosomal genes modulate MarA-mediated multidrug resistance in Escherichia coli., Antimicrob Agents Chemother 54(5):2125-34

 [9] Warner DM, Levy SB, 2010, Different effects of transcriptional regulators MarA, SoxS and Rob on susceptibility of Escherichia coli to cationic antimicrobial peptides (CAMPs): Rob-dependent CAMP induction of the marRAB operon., Microbiology (Reading), 156(Pt 2):570 10.1099/mic.0.033415-0

 [10] Keeney D, Ruzin A, McAleese F, Murphy E, Bradford PA, 2008, MarA-mediated overexpression of the AcrAB efflux pump results in decreased susceptibility to tigecycline in Escherichia coli., J Antimicrob Chemother, 61(1):46 10.1093/jac/dkm397

 [11] Alekshun MN, Levy SB, 1999, The mar regulon: multiple resistance to antibiotics and other toxic chemicals., Trends Microbiol, 7(10):410 10.1016/s0966-842x(99)01589-9

 [12] White DG, Goldman JD, Demple B, Levy SB, 1997, Role of the acrAB locus in organic solvent tolerance mediated by expression of marA, soxS, or robA in Escherichia coli., J Bacteriol, 179(19):6122 10.1128/jb.179.19.6122-6126.1997

 [13] Alekshun MN, Levy SB, 1997, Regulation of chromosomally mediated multiple antibiotic resistance: the mar regulon., Antimicrob Agents Chemother, 41(10):2067 10.1128/AAC.41.10.2067

 [14] Pomposiello PJ., Bennik MH., Demple B., 2001, Genome-wide transcriptional profiling of the Escherichia coli responses to superoxide stress and sodium salicylate., J Bacteriol 183(13):3890-902

 [15] Barbosa TM, Levy SB, 2000, Differential expression of over 60 chromosomal genes in Escherichia coli by constitutive expression of MarA., J Bacteriol, 182(12):3467 10.1128/JB.182.12.3467-3474.2000

 [16] Alekshun MN, Levy SB, Mealy TR, Seaton BA, Head JF, 2001, The crystal structure of MarR, a regulator of multiple antibiotic resistance, at 2.3 A resolution., Nat Struct Biol, 8(8):710 10.1038/90429

 [17] Cohen SP, Levy SB, Foulds J, Rosner JL, 1993, Salicylate induction of antibiotic resistance in Escherichia coli: activation of the mar operon and a mar-independent pathway., J Bacteriol, 175(24):7856 10.1128/jb.175.24.7856-7862.1993

 [18] Hächler H, Cohen SP, Levy SB, 1991, marA, a regulated locus which controls expression of chromosomal multiple antibiotic resistance in Escherichia coli., J Bacteriol, 173(17):5532 10.1128/jb.173.17.5532-5538.1991

 [19] Sulavik MC., Gambino LF., Miller PF., 1995, The MarR repressor of the multiple antibiotic resistance (mar) operon in Escherichia coli: prototypic member of a family of bacterial regulatory proteins involved in sensing phenolic compounds., Mol Med 1(4):436-46

 [20] Alekshun MN, Levy SB, 1999, Alteration of the repressor activity of MarR, the negative regulator of the Escherichia coli marRAB locus, by multiple chemicals in vitro., J Bacteriol, 181(15):4669 10.1128/JB.181.15.4669-4672.1999

 [21] Wilkinson SP, Grove A, 2006, Ligand-responsive transcriptional regulation by members of the MarR family of winged helix proteins., Curr Issues Mol Biol, 8(1):51 None

 [22] Chubiz LM, Glekas GD, Rao CV, 2012, Transcriptional cross talk within the mar-sox-rob regulon in Escherichia coli is limited to the rob and marRAB operons., J Bacteriol, 194(18):4867 10.1128/JB.00680-12

 [23] Duval V, McMurry LM, Foster K, Head JF, Levy SB, 2013, Mutational analysis of the multiple-antibiotic resistance regulator MarR reveals a ligand binding pocket at the interface between the dimerization and DNA binding domains., J Bacteriol, 195(15):3341 10.1128/JB.02224-12

 [24] McMurry LM, Levy SB, 2013, Amino acid residues involved in inactivation of the Escherichia coli multidrug resistance repressor MarR by salicylate, 2,4-dinitrophenol, and plumbagin., FEMS Microbiol Lett, 349(1):16 10.1111/1574-6968.12291

 [25] Chubiz LM, Rao CV, 2010, Aromatic acid metabolites of Escherichia coli K-12 can induce the marRAB operon., J Bacteriol, 192(18):4786 10.1128/JB.00371-10

 [26] Martin RG., Jair KW., Wolf RE., Rosner JL., 1996, Autoactivation of the marRAB multiple antibiotic resistance operon by the MarA transcriptional activator in Escherichia coli., J Bacteriol 178(8):2216-23

 [27] Linde HJ., Notka F., Metz M., Kochanowski B., Heisig P., Lehn N., 2000, In vivo increase in resistance to ciprofloxacin in Escherichia coli associated with deletion of the C-terminal part of MarR., Antimicrob Agents Chemother 44(7):1865-8

 [28] Zhu R, Hao Z, Lou H, Song Y, Zhao J, Chen Y, Zhu J, Chen PR, 2017, Structural characterization of the DNA-binding mechanism underlying the copper(II)-sensing MarR transcriptional regulator., J Biol Inorg Chem, 22(5):685 10.1007/s00775-017-1442-7

 [29] Hulo N, Sigrist CJ, Le Saux V, Langendijk-Genevaux PS, Bordoli L, Gattiker A, De Castro E, Bucher P, Bairoch A, 2004, Recent improvements to the PROSITE database., Nucleic Acids Res, 32(Database issue):D134 10.1093/nar/gkh044

 [30] Alekshun MN, Kim YS, Levy SB, 2000, Mutational analysis of MarR, the negative regulator of marRAB expression in Escherichia coli, suggests the presence of two regions required for DNA binding., Mol Microbiol, 35(6):1394 10.1046/j.1365-2958.2000.01802.x

 [31] Egland PG, Harwood CS, 1999, BadR, a new MarR family member, regulates anaerobic benzoate degradation by Rhodopseudomonas palustris in concert with AadR, an Fnr family member., J Bacteriol, 181(7):2102 10.1128/JB.181.7.2102-2109.1999

 [32] Wu RY, Zhang RG, Zagnitko O, Dementieva I, Maltzev N, Watson JD, Laskowski R, Gornicki P, Joachimiak A, 2003, Crystal structure of Enterococcus faecalis SlyA-like transcriptional factor., J Biol Chem, 278(22):20240 10.1074/jbc.M300292200

 [33] Pérez-Rueda E, Collado-Vides J, 2001, Common history at the origin of the position-function correlation in transcriptional regulators in archaea and bacteria., J Mol Evol, 53(3):172 10.1007/s002390010207

 [34] Perez-Rueda E., Collado-Vides J., Segovia L., 2004, Phylogenetic distribution of DNA-binding transcription factors in bacteria and archaea., Comput Biol Chem 28(5-6):341-50

 [35] Doukyu N., Ishikawa K., Watanabe R., Ogino H., 2012, Improvement in organic solvent tolerance by double disruptions of proV and marR genes in Escherichia coli., J Appl Microbiol 112(3):464-74

 [36] Oh HY, Lee JO, Kim OB, 2012, Increase of organic solvent tolerance of Escherichia coli by the deletion of two regulator genes, fadR and marR., Appl Microbiol Biotechnol, 96(6):1619 10.1007/s00253-012-4463-8

 [37] Krisko A, Copic T, Gabaldón T, Lehner B, Supek F, 2014, Inferring gene function from evolutionary change in signatures of translation efficiency., Genome Biol, 15(3):R44 10.1186/gb-2014-15-3-r44

 [38] Wang Y, Su Z, Wang L, Dong J, Xue J, Yu J, Wang Y, Hua X, Wang M, Zhang C, Liu F, 2017, SERS Assay for Copper(II) Ions Based on Dual Hot-Spot Model Coupling with MarR Protein: New Cu2+-Specific Biorecognition Element., Anal Chem, 89(12):6392 10.1021/acs.analchem.6b05106

 [39] Praski Alzrigat L, Huseby DL, Brandis G, Hughes D, 2021, Resistance/fitness trade-off is a barrier to the evolution of MarR inactivation mutants in Escherichia coli., J Antimicrob Chemother, 76(1):77 10.1093/jac/dkaa417

 [40] Deochand DK, Grove A, 2017, MarR family transcription factors: dynamic variations on a common scaffold., Crit Rev Biochem Mol Biol, 52(6):595 10.1080/10409238.2017.1344612

 [41] Domain F, Bina XR, Levy SB, 2007, Transketolase A, an enzyme in central metabolism, derepresses the marRAB multiple antibiotic resistance operon of Escherichia coli by interaction with MarR., Mol Microbiol, 66(2):383 10.1111/j.1365-2958.2007.05928.x

 [42] No authors listed, 2020, Retraction., Mol Microbiol, 113(4):859 10.1111/mmi.14487

 [43] Domain F, Levy SB, 2010, GyrA interacts with MarR to reduce repression of the marRAB operon in Escherichia coli., J Bacteriol, 192(4):942 10.1128/JB.01259-09

 [44] Francis Domain, Stuart B. Levy, 2011, GyrA interacts with MarR to reduce repression of the marRAB operon in Escherichia coli., J Bacteriol, 193(10):2674 10.1128/JB.00312-11



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