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Review

The TetR Family of Regulators

Leslie Cuthbertson, Justin R. Nodwell
Leslie Cuthbertson
Department of Biochemistry and Biomedical Sciences and M. G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada
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Justin R. Nodwell
Department of Biochemistry and Biomedical Sciences and M. G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, CanadaDepartment of Biochemistry, University of Toronto, Toronto, Ontario, Canada
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DOI: 10.1128/MMBR.00018-13
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  • Fig 1
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    Fig 1

    TFRs are known to interact with an exceptionally diverse set of small molecules, including antibiotics, metabolites, and cell-cell signaling molecules.

  • Fig 2
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    Fig 2

    TetR regulates the expression of the tetracycline resistance determinant encoded by tetA. (A) In the absence of tetracycline, a pair of TetR dimers bind to repeated palindromic sequences in the intergenic region between tetR and tetA. (B) When present, tetracycline is bound by TetR, causing a conformational change such that TetR can no longer bind DNA. This allows for expression of the tetracycline efflux pump encoded by tetA.

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    Fig 3

    Distribution of TFRs in sequenced genomes. Large genomes with a low number of TFRs are highlighted with a yellow box.

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    Fig 4

    Classification of TFRs based on the orientation and proximity of adjacent genes. (A) Type I TFRs are transcribed divergently from an adjacent gene. A regulatory relationship is predicted when this intergenic region is less than 200 bp. (B) Type II TFRs are predicted to be cotranscribed with and to regulate an adjacent gene based on a distance of less than 35 bp between genes. (C) Type III TFRs show neither of the above-described relationships with adjacent genes, and a regulatory relationship with the adjacent genes cannot be predicted.

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    Fig 5

    Phylogenomics can be used to predict small-molecule ligands for TFRs of unknown function. (A) The TFR of unknown function SSQG_00958 is predicted to bind a polyether ionophore based on grouping with MonRII and SchR3. (B) TFRs encoded in the biosynthesis clusters for macrolactam antibiotics cluster together, leading to the prediction that all of the TFRs in this group interact with macrolactam antibiotics. (C) AefR may recognize a phytosterol based on clustering with BreR. (Adapted from reference 25.)

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    Fig 6

    Combining information from genomic context with phylogenomics can also lead to ligand predictions for TFRs. (A and C) All of the TFRs in the group shown (A) (data are from reference 25) are type I TFRs predicted to regulate genes involved in streptogramin resistance (C). (B) Structure of the streptogramin antibiotic pristinamycin.

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    Fig 7

    TFRs share nine conserved α helices. In the front view, the DNA-binding domain is made up of helices 1 to 3. In the side view, helices 5 to 7 in the ligand-binding domain form a central triangle. In the top view, helices 8 and 9 from each monomer form a four-helical bundle that makes up the dimer interface. The structure of Rha06780 (PDB ID 2NX4) is shown, as it shows a structure typical of TFRs (24).

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    Fig 8

    TFRs display different ligand entry points. Based on current TFR-ligand structures, the ligand-binding cavity may be accessible from the side (e.g., ActR), front (e.g., SimR), or top (e.g., DesT) of the TFR. In some structures (e.g., RolR), the ligand is not accessible to the external environment and the entry point cannot be determined. SlmA interacts with a protein rather than a small-molecule ligand. Residues involved in protein-protein interactions are colored in red.

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    Fig 9

    Grouping of TFRs involved in antibiotic resistance. (A and B) KijA8 and KijR (A) and VarR and Pip (B) group together in phylogenomics analysis, indicating that KijR and Pip may have been horizontally acquired from an antibiotic-producing organism. (C) Many TFRs controlling the expression of multidrug efflux pumps cluster together in phylogenomics analysis. (Adapted from reference 25.)

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    Fig 10

    All known TFRs involved in gamma-butyrolactone (GBL) signaling form a single group (data are from reference 25). Within the GBL group, a subclade of TFRs known as the “pseudo”-GBL receptors are highlighted with a yellow box.

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    Fig 11

    TFRs involved in nitrogen metabolism. (A) Homologs of AmtR, a global regulator of nitrogen metabolism in Corynebacterium, may act as local regulators in related organisms. (B) RutR and PydR homologs from separate clades within a larger group of TFRs predicted to be involved in nucleotide metabolism. (C) Homologs of XdhR may be involved in purine metabolism. (Adapted from reference 25.)

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    Fig 12

    TFRs involved in lipid metabolism. TFRs involved in lipid metabolism are found in many groups. (A to C) TFRs involved in fatty acid biosynthesis and degradation. (D) TFRs regulating fatty acid saturation. (E) TFRs involved in the synthesis and degradation of storage polymers. (F and G) TFRs involved in terpene utilization. (Adapted from reference 25.)

Tables

  • Figures
  • Table 1

    Major families of one-component signal transduction systems

    One-component systemDefining featuresReference(s)
    AraC/XlySInvolved in regulating pathways for the catabolism of various sugars, primarily transcriptional activators, C-terminal DNA-binding domain196
    ArgRInvolved in regulating amino acid metabolism, typically function as transcriptional repressors, N-terminal DNA-binding domain197
    ArsR/SmtBInvolved in regulating metal homeostasis, primarily transcriptional repressors, DNA-binding domain located near the center of the protein198
    AsnC/LrpInvolved in regulating amino acid metabolism, function as both transcriptional activators and repressors, N-terminal DNA-binding domain199
    Crp/FnrInvolved in regulating many cellular processes, may function as activators and repressors, C-terminal DNA-binding domain200
    DeoRInvolved in regulating sugar metabolism, typically function as repressors, N-terminal DNA-binding domain201
    DtxRInvolved in regulating metal homeostasis, primarily transcriptional repressors, N-terminal DNA-binding domain202
    FurInvolved in regulating metal homeostasis, primarily transcriptional repressors, N-terminal DNA-binding domain202
    GntRInvolved in regulating numerous cellular processes, typically function as transcriptional repressors, N-terminal DNA-binding domain203
    IclRInvolved in regulating carbon metabolism, function as both transcriptional activators and repressors, N-terminal DNA-binding domain204
    LacIInvolved in regulating carbon metabolism, typically function as transcriptional repressors, N-terminal DNA-binding domain205
    LuxRInvolved in regulating quorum sensing, typically function as activators, C-terminal DNA-binding domain206
    LysRInvolved in regulating many cellular processes, function as both activators and repressors, N-terminal DNA-binding domain207
    MarRInvolved in regulating antibiotic resistance, typically function as transcriptional repressors, DNA-binding domain located near the center of the protein208
    MerRInvolved in regulating metal homeostasis, typically function as transcriptional repressors, N-terminal DNA-binding domain209
    MetJInvolved in regulating many cellular processes, typically function as transcriptional repressors, N-terminal DNA-binding domain3
    ModEInvolved in regulating metal homeostasis, function as both transcriptional activators and repressors, N-terminal DNA-binding domain210
    PadRPoorly characterized family, N-terminal DNA-binding domain211
    TetRInvolved in regulating antibiotic resistance, typically function as repressors, N-terminal DNA-binding domain14
    XreInvolved in regulating various cellular processes, typically function as transcriptional repressors, N-terminal DNA-binding domain212, 213
  • Table 2

    TFRs of known function

    TFROrganismDescriptionaKnown ligand(s)PDB IDReference(s)
    AbyCVerrucosispora maris AB-18-032Located in the abyssomicin biosynthesis cluster; predicted to regulate abyD encoding a MFS export pump; mutation decreases abyssomicin synthesis214
    AcmG5Streptomyces iakyrusLocated in the actinomycin G biosynthesis cluster215
    AcmPStreptomyces chrysomallus ATCC 11523Located in the actinomycin D biosynthesis cluster94
    AcmUStreptomyces chrysomallus ATCC 11523Located in the actinomycin D biosynthesis cluster94
    AcnRCorynebacterium glutamicumRegulates the aconitase (acn) gene4AC6, 4ACI, 4AF5145
    AcrREscherichia coliRegulator of the AcrAB multidrug efflux pumpRhodamine 6G, ethidium, proflavine3BCG, 3LHQ, 2QOP112, 116
    AcrR-likeEscherichia coli, Streptococcus uberisPutative regulator of rdmC and mph(B) genes involved in spiramycin and tylosin resistance103, 216
    ActR (SCO5082)Streptomyces coelicolorLocated in the actinorhodin biosynthesis cluster; regulates expression of the ActA and ActB efflux pumpsActinorhodin, (S)-DNPA2OPT, 3B6C, 3B6A79
    AcuRAlcaligenes faecalisPutative repressor for genes involved in dimethylsulfoniopropionate and acrylate catabolism217
    AcuRRhodobacter sphaeroidesRegulates expression of AcuI and DddL involved in dimethylsulfoniopropionate and acrylate catabolismAcrylate218
    AdeNAcinetobacter baumanniiRegulator of the AdeIJK efflux pump219
    AefRPseudomonas syringaeRegulates AHL production and is required for plant colonization3CDL40
    AguRPseudomonas aeruginosa PAO1Regulates AguBA required for agmatine utilizationAgmatine181
    AlnR2Streptomyces sp. strain CM020Located in the alnumycin biosynthesis cluster220
    AlpWStreptomyces ambofaciensLocated in the alpomycin biosynthesis cluster and involved in the regulation of kinamycin biosynthesis; similar to gamma-butyrolactone receptors221
    AlpZStreptomyces ambofaciensLocated in the alpomycin biosynthesis cluster; similar to gamma-butyrolactone receptors222
    AmeRAgrobacterium tumefaciensRegulates the tripartite RND exporter AmeABC223
    AmiPStreptomyces vinaceus-drappusLocated in the amicetin biosynthesis cluster95
    AmtRCorynebacterium glutamicumGlobal regulator of nitrogen control metabolismGlnK37
    Ang8Streptomyces sp. strain W007Located in an angucyclinone biosynthesis cluster224
    ArpAStreptomyces griseusInvolved in the regulation of antibiotic production and sporulationA-factor (GBL)225
    ArpRPseudomonas putida S12Regulates the ArpABC efflux pump involved in the export of multiple antibiotics226
    Asm2Actinosynnema pretiosumLocated in the ansamitocin biosynthesis cluster and involved in the regulation of ansamitocin biosynthesis227
    Asm29Actinosynnema pretiosumLocated in the ansamitocin biosynthesis cluster and involved in the regulation of ansamitocin biosynthesis227
    AtrAStreptomyces coelicolorPleiotropic regulator of antibiotic biosynthesis6
    AtuRPseudomonas aeruginosaRegulates genes required for acyclic terpene utilization174
    Aur1BStreptomyces aureofaciens CCM 3239Located in the auricin biosynthesis cluster228
    Aur1RStreptomyces aureofaciens CCM 3239Located in the auricin biosynthesis cluster; similar to gamma-butyrolactone receptors229
    AvaR1Streptomyces avermitilisRegulator of avermectin biosynthesis; similar to gamma-butyrolactone receptorsAvenolide127
    AvaR2Streptomyces avermitilisSimilar to gamma-butyrolactone receptors230
    AvaR3Streptomyces avermitilisPleiotropic regulator of antibiotic production; similar to gamma-butyrolactone receptors230
    AveIStreptomyces avermitilisOrtholog of AtrA; regulator of antibiotic production231
    Azi42Streptomyces sahachiroiLocated adjacent to the azinomycin B biosynthetic gene cluster; thought to be beyond the boundaries of the cluster232
    BarAStreptomyces virginiaeInvolved in the regulation of virginiamycin; similar to gamma-butyrolactone-binding proteinsVirginiae butanolide (GBL)233
    BarBStreptomyces virginiaeInvolved in the regulation of virginiamycin; similar to gamma-butyrolactone-binding proteins234
    BarZStreptomyces virginiaeLocated in the virginiamycin biosynthesis cluster; similar to gamma-butyrolactone-binding proteins235
    BdcR (YjgJ)Escherichia coliRegulator of BdcA expression28
    BecMStreptomyces sp. strain DSM 21069Located in the biosynthesis cluster for macrolactam BE-14106 biosynthesis236
    BepRBrucella suisRegulator of the BepDE efflux pumpDeoxycholate237
    BetIEscherichia coliRegulates expression of BetT, BetA, and BetB required for the synthesis of glycine betaine from cholineCholine238
    BioQCorynebacterium glutamicum ATCC 13032Regulates biotin biosynthesis and import189
    BpeRBurkholderia pseudomalleiRegulates the BpeAB-OprB multidrug efflux pump239
    BreRVibrio choleraeRegulates the BreAB efflux pump in response to bileDeoxycholate39
    BrpStreptomyces clavuligerusGamma-butyrolactone receptor involved in the regulation of clavulanic acid and cephamycin C biosynthesis240
    BrtAListeria monocytogenesRegulator of the MdrT efflux pumpCholate241
    BspRBurkholderia pseudomalleiInvolved in regulating type III secretion systems242
    BtrR1Bacillus circulansLocated in the butirosin biosynthesis cluster and involved in regulation243
    CalR1Micromonospora echinosporaLocated in the calicheamicin biosynthesis cluster244
    CampRRhodococcus sp. strain NCIMB 9784Divergent to camK (6-oxocamphor hydrolase)177
    CamRPseudomonas putidaRegulator of camphor degradation245
    CasRRhizobium etliRegulator of CasA required for colonization and infection of the host246
    CgmR (cg2894, Cgl2612)Corynebacterium glutamicumMultidrug resistance-related transcription factorEthidium bromide, malachite green2ZOY, 2ZOZ, 2YVH, 2YVE43, 247
    ChlF1Streptomyces antibioticusLocated in the chlorothricin biosynthetic gene cluster248
    ChryX5Streptomyces albaduncusLocated in the chrysomycin biosynthesis cluster; a homolog is not present in the cluster for the related molecule ravidomycin249
    CifRPseudomonas aeruginosaRegulator of the Cif toxinEpibromohydrin250
    CmeRCampylobacter jejuniRegulator of the CmeABC efflux pumpTaurocholate, cholate, salicylate2QCO, 3QPS, 3QQA56
    CmtIPseudomonas putidaPutative regulator of operons required for p-cymene/p-cumate degradation175
    CmtRPseudomonas putidaPutative regulator of operons required for p-cymene/p-cumate degradation178
    ComREscherichia coliRegulator of ComC involved in copper permeabilityCopper72
    CprAStreptomyces coelicolorSimilar to gamma-butyrolactone receptors; involved in regulating sporulation and antibiotic production134
    CprBStreptomyces coelicolorSimilar to gamma-butyrolactone receptors; involved in regulating sporulation and antibiotic production1IU5, 1IU6134
    CprSStreptomyces coelicolorSimilar to gamma-butyrolactone receptors251
    CymRPseudomonas putidaRegulator of the cym and cmt operons required for p-cymene and p-cumate degradationp-Cumate176
    DarR (MSMEG_5346)Mycobacterium smegmatisFirst cyclic-di-AMP-responsive transcription factor to be identified in bacteriaCyclic-di-AMP142
    DddHHalomonas sp. strain HTNK1Putative regulator of genes required for dimethylsulfoniopropionate and acrylate catabolism252
    DesTPseudomonas aeruginosaRegulates the expression of the DesCB acyl-CoA desaturase operonOleate (corepressor), stearate (inducer)3LSJ, 3LSR, 3LSP166
    DhaRRhodococcus rhodochrousRegulator of haloalkane dehalogenase (DhaA)143
    DhaSLactococcus lactisRegulator of the dha operon; functions as a transcriptional activatorDhaQ-dihydroxyacetone complex2IU569
    EbrRStreptomyces lividansRegulator of the EbrA efflux pump3HTJ, 3HTI, 3HTH, 3HTA253
    EbrSStreptomyces lividansRegulator of the EbrC efflux pump254
    Ecm10Streptomyces lasaliensisLocated in the echinomycin biosynthesis cluster255
    EmhRPseudomonas fluorescensRegulates the EmhABC efflux pump that influences production of 2,4-diacetylphloroglucinol and is required for phenanthrene, anthracene, and fluoranthene efflux256, 257
    EncSStreptomyces maritimusLocated in the enterocin biosynthesis gene cluster258
    EnvR (AcrS)Escherichia coliDivergent to the AcrEF efflux pump; may function as a switch for the alternative expression of AcrAB and AcrEF efflux pumps259
    EpeRStreptomyces clavuligerusControls expression of the EpeA efflux pump260
    EsmT4Streptomyces antibioticus Tu 2706Located in the esmeraldin biosynthesis cluster261
    EthRMycobacterium tuberculosisRegulator of ethA encoding a monooxygenase required for the activation of ethionamideHexadecyl octanoate1T5658
    FabREscherichia coliRegulator of genes required for unsaturated fatty acid synthesisUnsaturated thioesters165
    Fad35R (Rv2506)Mycobacterium tuberculosisRegulator of Fad35 acyl-CoA synthetasePalmitoyl-CoA162
    FadR (YsiA)Bacillus subtilisRegulator of fatty acid catabolismLong-chain acyl-CoAs1VIO161
    FadRPseudonocardia autotrophicaRegulates fad genes required for fatty acid degradation158
    FadRThermus thermophilusRegulator of genes required for fatty acid degradationMedium to long (C10 to C18) straight-chain fatty acyl-CoAs3ANG, 3ANP150
    FarAStreptomyces sp. strain FRI-5Gamma-butyrolactone autoregulator that controls antibiotic productionIM-2 (GBL)262
    FasRCorynebacterium glutamicumRegulator of accD1 and fasA expression required for lipid synthesis157
    FrrABradyrhizobium japonicumRegulator of the FreABC efflux pumpGenistein, daidzein263
    HapRVibrio choleraeMaster quorum-sensing regulator2PBX264
    HemRPropionibacterium freudenreichiiPossible regulator of hem gene expression required for the conversion of glutamate to protoheme190
    HlyIIRBacillus cereusRegulator of hemolysin II expression265
    HnoR (HdnoR)Arthrobacter nicotinovoransRepressor of 6-hydroxy-d-nicotine oxidase6-Hydroxy-d- and 6-hydroxy-l-nicotine266
    HrtRLactococcus lactisRegulator of the HrtB-HtrA transporterHeme3VP5, 3VP5, 3VOX191, 46
    IcaRStaphylococcus epidermidisRegulator of the ica operon required for biofilm formation2ZCM, 2ZCN267
    IfeRAgrobacterium tumefaciensRegulator of the IfeAB efflux pump268
    JadR*Streptomyces venezuelaeLocated in the jadomycin biosynthesis cluster269
    JadR2Streptomyces venezuelaeSimilar to gamma-butyrolactone receptors; involved in the regulation of jadomycin biosynthesisJadomycin and chloramphenicol133, 270
    KanGStreptomyces kanamyceticusLocated near the kanamycin biosynthesis cluster but probably beyond cluster boundaries271
    KijA8Actinomadura kijaniataLocated in the kijanimicin biosynthesis clusterKijanimicin272
    KijC5Actinomadura kijaniataLocated in the kijanimicin biosynthesis cluster272
    KijRStreptomyces coelicolorRegulator of KijX expression and kijanimicin resistanceKijanimicin, saccharocarcins A and B25
    KinRStreptomyces murayamaensisLocated in the kinamycin biosynthesis cluster273
    KirRIIStreptomyces collinusLocated in the kirromycin biosynthesis cluster274
    KsbAKitasatospora setaeGamma-butyrolactone receptor protein; involved in regulating bafilomycin biosynthesisGBLs275
    KstRMycobacterium tuberculosisRegulator of lipid metabolism3MNL169
    KstR2Mycobacterium tuberculosisRegulator of cholesterol metabolism170
    LanKStreptomyces cyanogenusLocated in the landomycin biosynthetic pathwayLandomycin A and intermediates78
    Lct13Streptomyces rishiriensisPutative gamma-butyrolactone receptor protein; located in the lactonamycin biosynthesis cluster276
    Lct14Streptomyces rishiriensisPutative gamma-butyrolactone receptor protein; located in the lactonamycin biosynthesis cluster276
    LfrRMycobacterium smegmatisRegulator of LfrA multidrug efflux pumpProflavine2WGB, 2V5755
    LitRVibrio fischeriInvolved in regulating luminescence and symbiotic light organ colonization277
    LiuQ (Bamb_4589)Burkholderia ambifaria AMMDRegulator of branched-chain amino acid degradation183
    LmrABacillus subtilisRegulator of the LmrB efflux pumpFlavonoids (quercetin, fisetin, galangin, catechin, coumestrol, genistein)104
    LplRRhodococcus erythropolisRegulator of l-pantoyl lactone dehydrogenase gene expression278
    LuxRVibrio harveyiGlobal regulator279
    LuxTVibrio harveyiGlobal regulator280
    McbRCorynebacterium glutamicumGlobal regulator of l-methionine and l-cysteine biosynthesisS-Adenosylhomocysteine185
    Mce3RMycobacterium tuberculosisPutative regulator of lipid metabolism281
    MdoRMycobacterium sp. strain JC1Regulator of genes required for methanol oxidation147
    MedORF28Streptomyces sp. strain AM-7161Located in the medermycin biosynthesis cluster282
    MepRPseudomonas putidaRegulates efflux pump involved in toluene resistance283
    MerOStreptomyces sp. strain NRRL 30748Located in the meridamycin biosynthesis cluster284
    MexLPseudomonas aeruginosaRegulator of the MexJK efflux pump285
    MexZ (AmrR)Pseudomonas aeruginosaRegulates the MexXY (AmrAB) exporter involved in aminoglycoside resistance2WUI286
    MlaMStreptomyces sp. strain MP39-85Located in the biosynthetic gene cluster for the macrocyclic lactam ML-44992
    MmfRStreptomyces coelicolorGamma-butyrolactone-like receptor involved in regulating methylenomycin production128, 287
    MmyRStreptomyces coelicolorGamma-butyrolactone-like receptor involved in regulating methylenomycin production128, 287
    MmyRStreptomyces violaceoruberLocated in the methylenomycin biosynthesis cluster288
    MnbRComamonas sp. strain JS46Putative regulator of mnb operon required for 3-nitrobenzoate oxidation144
    MonRIIStreptomyces cinnamonensisLocated in the monensin biosynthesis locus289
    MphREscherichia coliRegulator of macrolide resistance14-membered macrolides (erythromycin, oleandomycin)3G56, 3FRQ101
    MSMEG_6564Mycobacterium smegmatisGlobal regulator of DNA repair genes290
    MtrRNeisseria gonorrhoeaeRegulator of the mtr efflux pump3VIB291
    NalCPseudomonas aeruginosaIndirect regulator of the MexAB-OprM efflux pump through regulation of ArmR expressionChlorinated phenols292, 293, 294, 295
    NalDPseudomonas aeruginosaRegulator of the MexAB-OprM efflux pump296
    NapR3Streptomyces aculeolatusLocated in the napyradiomycin biosynthesis cluster297
    NapR7Streptomyces aculeolatusLocated in the napyradiomycin biosynthesis cluster297
    NcsR2Streptomyces carzinostaticusGamma-butyrolactone receptor located in the neocarzinostatin biosynthesis cluster298
    NcsR3Streptomyces carzinostaticusGamma-butyrolactone receptor located in the neocarzinostatin biosynthesis cluster298
    NcsR4Streptomyces carzinostaticusLocated in the neocarzinostatin biosynthesis cluster298
    NemR (YdhM)Escherichia coliRegulator of N-ethylmaleimide reductaseN-Ethylmaleimide and other Cys modification reagents299
    NfxBPseudomonas aeruginosaRegulator of the MexCD-OprJ efflux pump300
    NicSPseudomonas putidaRegulator of genes required for nicotinic acid degradationNicotinic acid and hydroxynicotinic acid148
    NonGStreptomyces griseusLocated near the nonactin biosynthesis cluster but probably beyond cluster boundaries301
    OpaRVibrio parahaemolyticusGlobal regulator301
    ORF20pStreptomyces hygroscopicusLocated in the geldanamycin biosynthesis locus
    OrfH2Streptomyces griseoruberLocated in the hedamycin biosynthesis locus302
    OvmYStreptomyces antibioticusLocated in the oviedomycin biosynthesis cluster303
    PaaRAzoarcus evansiiRegulator of genes required for phenyl acetic acid degradation304
    PaaRThermus thermophilusRegulator of genes required for phenyl acetic acid degradationPhenylacetyl coenzyme A150
    PapR3Streptomyces pristinaespiralisLocated in the pristinamycin biosynthesis cluster; similar to gamma-butyrolactone receptors305
    PapR5Streptomyces pristinaespiralisLocated in the pristinamycin biosynthesis cluster; similar to gamma-butyrolactone receptors305
    PG1181Porphyromonas gingivalisExpressed in response to NO stress306
    PgaYStreptomyces sp. strain PGA64Located in the pga angucyclinone biosynthesis cluster307
    PhaDPseudomonas putidaRegulator of genes required for polyhydroxyalkanoate metabolism167
    PhlFPseudomonas fluorescensLocated in the 2,4-diacetylphloroglucinol biosynthesis cluster2,4-Diacetylphloroglucinol (inducer), salicylate (corepressor)75
    PhlHPseudomonas fluorescensLocated in the 2,4-diacetylphloroglucinol biosynthesis cluster308
    PigZSerratia sp. strain ATCC 39006Regulator of the ZrpADBC efflux pump309
    Pip (SCO4025)Streptomyces coelicolorRegulator of the Pep efflux pumpPristinamycin I100
    PksABacillus subtilisLocated in the bacillaene biosynthesis cluster310
    PlaR2Streptomyces sp. strain Tü6071Located in the phenalinolactone biosynthesis cluster311
    PltZPseudomonas sp. strain M18Located in the pyoluteorin biosynthesis cluster312
    PmeR (PSPTO_4302)Pseudomonas syringaeRegulator of MexAB-OprMFlavonoids313
    PqrA (SCO1568)Streptomyces coelicolorRegulator of the PqrB efflux pump314
    PsbIRhodopseudomonas palustrisRegulator of p-cumate catabolismp-Cumate179
    PsrAPseudomonas aeruginosaRegulator of the β-oxidation operonLong-chain fatty acids2FBQ163
    PydRPseudomonas putida KT2440Regulator of pyrimidine reductive catabolic pathway154
    Pyr27Actinosporangium vitaminophilumLocated in the pyrrolomycin biosynthesis cluster315
    Pyr3Actinosporangium vitaminophilumLocated in the pyrrolomycin biosynthesis cluster315
    PyrOStreptomyces pyridomyceticusLocated in the pyridomycin biosynthesis cluster; similar to gamma-butyrolactone receptors316
    QacRStaphylococcus aureusRegulator of the QacA efflux pumpRhodamine 6G, dequalinium, crystal violet, berberine, DiOC3, methyl green, benzalkonium, tetraphenylarsonium, nitidine, palmatine1JTX, 1JT6, 1JTY, 1JUM, 1JUP, 1JUS, 1JTO, 1QVT, 1QVU60, 53
    QdoR (YxaF)Bacillus subtilisRegulator of quercetin dioxygenase QdoI (YxaG)Flavonoids (quercetin, fisetin, tamarixetin, galangin, genistein, coumestrol)317
    RamR (STM0580)Salmonella enterica serovar TyphimuriumRegulator of the RamA efflux pump; mutations in the RamR binding site result in a multidrug resistance phenotype318
    RefZ (YttP)Bacillus subtilisInvolved in the switch from medial to polar cell division195
    RegEActinoplanes friuliensisLocated in (or adjacent to) the friulimicin biosynthesis cluster319
    RemMStreptomyces resistomycificusLocated in the resistomycin biosynthesis cluster320
    RemQStreptomyces resistomycificusLocated in the resistomycin biosynthesis cluster320
    RifQAmycolatopsis mediterraneiLocated in the rifamycin biosynthesis cluster91
    RkIStreptomyces strain sp. 88-682Located in the RK-682 biosynthesis cluster321
    RmiRRhizobium etliRegulator of NodTch322
    RmrRRhizobium etliRegulator of the RmrAB efflux pump323
    RolRCorynebacterium glutamicumRegulator of resorcinol degradationResorcinol3AQS, 3AQT49
    RphA3Streptomyces griseoviridisLocated in the prodigiosin biosynthesis cluster324
    RrdA (SCO1104)Streptomyces coelicolorRegulator of antibiotic production325
    RutR (YcdC)Escherichia coliRegulator of pyrimidine synthesisUracil326
    Rv3066Mycobacterium tuberculosisRegulator of Mmr multidrug efflux pumpEthidium3V6G, 3V78327
    SaaRStreptomyces ambofaciensGamma-butyrolactone receptor involved in regulating spiramycin production328
    SabRStreptomyces ansochromogenesGamma-butyrolactone receptor involved in regulating nikkomycin production329
    SabRStreptomyces acidiscabiesGamma-butyrolactone receptor involved in regulating WS5995B production330
    SabSStreptomyces acidiscabiesGamma-butyrolactone receptor involved in regulating WS5995B production330
    SACE_7040Saccharopolyspora erythraeaRegulator of morphological differentiation331
    SaqKMicromonospora sp. strain Tu 6368Located in the saquayamycin Z biosynthesis cluster83
    SAV3818Streptomyces avermitilisGlobal upregulator of antibiotic production in Streptomyces species332
    SbtRThermus thermophilus HB8Contains an intermolecular disulfide bridge that may be involved in ligand affinity3VUQ333
    SCAB1401Streptomyces scabiesLocated in the pyochelin biosynthesis cluster334
    ScbRStreptomyces coelicolorGamma-butyrolactone-binding protein; pleiotropic regulator of antibiotic productionSCB1251
    ScbR2Streptomyces coelicolorSimilar to gamma-butyrolactone-binding proteins; regulator of Cpk polyketide production and gamma-butyrolactone biosynthesisActinorhodin and undecylprodigiosin131, 132, 133
    SchA21Streptomyces sp. strain SCC-2136Located in the biosynthesis cluster for the angucyclinones Sch 47554 and Sch 47555335
    SchA4Streptomyces sp. strain SCC-2136Located in the biosynthesis cluster for the angucyclinones Sch 47554 and Sch 47555335
    SchR3Streptomyces chartreusisLocated in the biosynthesis cluster for calcimycin (A23187)93
    SCO0253Streptomyces coelicolorRegulator of SCO0252Tetracycline3FIW336
    SCO0332Streptomyces coelicolorRegulator of SCO03302ZB9337
    SCO1712Streptomyces coelicolorRegulator of antibiotic production3BNI338, 160
    SCO3201Streptomyces coelicolorRegulator of antibiotic production339
    SczAStreptococcus pneumoniaeRegulator of metal ion homeostasisZn2+71
    SfmR1Streptomyces lavendulaeLocated in the saframycin A biosynthesis cluster340
    SimRStreptomyces antibioticusLocated in the simocyclinone D8 biosynthesis clusterSimocyclinones D8 and C42Y2Z, 2Y30, 2Y3176
    SlgR1Streptomyces lydicusLocated in the streptolydigin biosynthesis cluster341
    SlmAEscherichia coliNucleoid occlusion factorFtsZ3NXC192, 193
    SmcRVibrio vulnificusGlobal regulator3KZ9342, 343
    SmeTStenotrophomonas maltophiliaRegulator of the SmeDEF efflux pumpTriclosan2W5352, 61, 344
    SMU_1349Streptococcus mutansRegulator of the TnSmu2 operon, which contains a secondary metabolite biosynthesis gene cluster345, 346
    SngRStreptomyces natalensisGamma-butyrolactone receptor protein involved in regulating natamycin biosynthesis and sporulation347
    SocA3Myxococcus xanthusInvolved in regulating morphological development348
    SpbRStreptomyces pristinaespiralisGamma-butyrolactone receptor protein involved in regulating pristinamycin biosynthesis and sporulation349, 305
    SrpRPseudomonas putidaRegulator of the SrpABC efflux pumpSrpS350, 351
    SrrAStreptomyces rocheiGamma-butyrolactone receptor protein involved in regulating lankacidin and lankamycin biosynthesis and sporulation352, 353
    SrrBStreptomyces rocheiGamma-butyrolactone receptor protein involved in regulating lankacidin and lankamycin biosynthesis and sporulation352
    SrrCStreptomyces rocheiGamma-butyrolactone receptor protein involved in regulating lankacidin and lankamycin biosynthesis and sporulation352
    SscRStreptomyces scabiesGamma-butyrolactone receptor protein involved in regulating secondary metabolismGBLs354
    SsfT2Streptomyces sp. strain SF2575Located in the biosynthesis cluster for the polyketide SF257599
    Strop_2766Salinispora tropicaLocated in the salinilactam biosynthesis cluster355
    TamKStreptomyces sp. strain 307-9Located in the tirandamycin biosynthesis cluster356
    SwrTVibrio parahaemolyticusOrtholog of V. harveyi LuxT; regulator of swarming motility357
    TarAStreptomyces tendaeGamma-butyrolactone receptor protein involved in regulating nikkomycin production358
    TcaR2Micromonospora chalceaLocated in the tetrocarcin A biosynthesis cluster359
    TcmRStreptomyces glaucescensLocated in the tetracenomycin C biosynthesis cluster360
    Tei8Actinoplanes teichomyceticusLocated in the teicoplanin biosynthesis cluster361
    TetREscherichia coliRegulator of tetracycline resistanceTetracycline2TCT, 1QPI362
    TetRArthrobacter oxydansPutative regulator of genes required for phenyl acetic acid degradation363
    TetRStreptomyces toxytriciniPutative regulator of the propionyl-CoA carboxylase complex364
    Tmn21Streptomyces sp. strain NRRL 11266Located in the tetronomycin biosynthesis cluster365
    TRMycobacterium peregrinumPutative regulator of macrolide resistance366
    TrdKStreptomyces sp. strain SCSIO1666Located in the tirandamycin biosynthesis cluster367
    Tsn22Streptomyces longisporoflavusLocated in the tetronasin biosynthesis clusterGenBank accession no. FJ462704
    TtgRPseudomonas putidaRegulator of the TtgABC efflux pumpPhloretin, naringenin, chloramphenicol, tetracycline, quercetin, luteolin2UXP, 2UXI, 2UXH, 2UXU, 2UXO51, 368, 369
    TtgWPseudomonas putidaDivergent to the TtgGHI efflux pump but does not play a major role in regulation370
    TvrRPseudomonas syringaeRequired for pathogenesis371
    TylPStreptomyces fradiaeGamma-butyrolactone receptor protein involved in regulating tylosin production and sporulation372, 373
    TylQStreptomyces fradiaeGamma-butyrolactone receptor protein involved in regulating tylosin production373
    UidREscherichia coliRegulator of the d-glucuronidase UidA374
    UrdKStreptomyces fradiaeLocated in the urdamycin biosynthesis cluster84
    VanTVibrio (Listonella) anguillarumGlobal regulator375
    VarRStreptomyces virginiaeLocated in the virginiamycin biosynthesis clusterVirginiamycin S77
    VceRVibrio choleraeRegulator of VceCAB efflux pumpCarbonyl cyanide m-chlorophenyl hydrazone376
    VexRVibrio choleraeRegulates the VexAB efflux pump which is expressed in response to bile, sodium dodecyl sulfate, or novobiocin39
    VlmEStreptomyces viridifaciensLocated in the valanimycin biosynthesis cluster377
    VtpRVibrio tubiashiiGlobal regulator of virulence factors378
    XdhR (SCO1135)Streptomyces coelicolorRegulator of xanthine dehydrogenase156
    • ↵a MFS, major facilitator superfamily; AHL, acyl-homoserine lactone.

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The TetR Family of Regulators
Leslie Cuthbertson, Justin R. Nodwell
Microbiology and Molecular Biology Reviews Sep 2013, 77 (3) 440-475; DOI: 10.1128/MMBR.00018-13

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The TetR Family of Regulators
Leslie Cuthbertson, Justin R. Nodwell
Microbiology and Molecular Biology Reviews Sep 2013, 77 (3) 440-475; DOI: 10.1128/MMBR.00018-13
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  • Top
  • Article
    • SUMMARY
    • INTRODUCTION
    • TetR FAMILY REGULATORS
    • GENOMICS OF TFRs
    • TFR STRUCTURAL BIOLOGY
    • TFRs AND ANTIBIOTIC RESISTANCE
    • TFRs AND CELL-CELL SIGNALING
    • TFRs AND CARBON METABOLISM
    • TFRs AND NITROGEN METABOLISM
    • TFRs AND LIPID METABOLISM
    • TFRs AND AMINO ACID METABOLISM
    • TFRs AND COFACTOR METABOLISM
    • TFRs AND CELL DIVISION
    • FUTURE DIRECTIONS AND CHALLENGES
    • ACKNOWLEDGMENTS
    • REFERENCES
    • Author Bios
  • Figures & Data
  • Info & Metrics
  • PDF

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