4jba › Citations

The multiple antibiotic resistance regulator MarR is a copper sensor in Escherichia coli.

Hao Z, Lou H, Zhu R, Zhu J, Zhang D, Zhao BS, Zeng S, Chen X, Chan J, He C, Chen PR
Nat Chem Biol 10 21-8 (2014)
Cited: 82 times
EuropePMC logo PMID: 24185215

Abstract

The widely conserved multiple antibiotic resistance regulator (MarR) family of transcription factors modulates bacterial detoxification in response to diverse antibiotics, toxic chemicals or both. The natural inducer for Escherichia coli MarR, the prototypical transcription repressor within this family, remains unknown. Here we show that copper signaling potentiates MarR derepression in E. coli. Copper(II) oxidizes a cysteine residue (Cys80) on MarR to generate disulfide bonds between two MarR dimers, thereby inducing tetramer formation and the dissociation of MarR from its cognate promoter DNA. We further discovered that salicylate, a putative MarR inducer, and the clinically important bactericidal antibiotics norfloxacin and ampicillin all stimulate intracellular copper elevation, most likely through oxidative impairment of copper-dependent envelope proteins, including NADH dehydrogenase-2. This membrane-associated copper oxidation and liberation process derepresses MarR, causing increased bacterial antibiotic resistance. Our study reveals that this bacterial transcription regulator senses copper(II) as a natural signal to cope with stress caused by antibiotics or the environment.

Articles - 4jba mentioned but not cited (1)

  1. Crystal structure of a MarR family protein from the psychrophilic bacterium Paenisporosarcina sp. TG-14 in complex with a lipid-like molecule. Hwang J, Park SH, Lee CW, Do H, Shin SC, Kim HW, Lee SG, Park HH, Kwon S, Lee JH. IUCrJ 8 842-852 (2021)


Reviews citing this publication (17)

  1. Unraveling the physiological complexities of antibiotic lethality. Dwyer DJ, Collins JJ, Walker GC. Annu. Rev. Pharmacol. Toxicol. 55 313-332 (2015)
  2. Recent developments in copper and zinc homeostasis in bacterial pathogens. Braymer JJ, Giedroc DP. Curr Opin Chem Biol 19 59-66 (2014)
  3. Co-Selection of Resistance to Antibiotics, Biocides and Heavy Metals, and Its Relevance to Foodborne Pathogens. Wales AD, Davies RH. Antibiotics (Basel) 4 567-604 (2015)
  4. MarR family transcription factors: dynamic variations on a common scaffold. Deochand DK, Grove A. Crit. Rev. Biochem. Mol. Biol. 52 595-613 (2017)
  5. At the Nexus of Antibiotics and Metals: The Impact of Cu and Zn on Antibiotic Activity and Resistance. Poole K. Trends Microbiol. 25 820-832 (2017)
  6. Metallochaperones and metalloregulation in bacteria. Capdevila DA, Edmonds KA, Giedroc DP. Essays Biochem. 61 177-200 (2017)
  7. Metalloallostery and Transition Metal Signaling: Bioinorganic Copper Chemistry Beyond Active Sites. Pham VN, Chang CJ. Angew Chem Int Ed Engl 62 e202213644 (2023)
  8. Allosteric control of metal-responsive transcriptional regulators in bacteria. Baksh KA, Zamble DB. J Biol Chem 295 1673-1684 (2020)
  9. MarR family proteins are important regulators of clinically relevant antibiotic resistance. Beggs GA, Brennan RG, Arshad M. Protein Sci 29 647-653 (2020)
  10. Transcriptional Regulation of the Multiple Resistance Mechanisms in Salmonella-A Review. Wójcicki M, Świder O, Daniluk KJ, Średnicka P, Akimowicz M, Roszko MŁ, Sokołowska B, Juszczuk-Kubiak E. Pathogens 10 801 (2021)
  11. MarR Family Transcription Factors from Burkholderia Species: Hidden Clues to Control of Virulence-Associated Genes. Gupta A, Pande A, Sabrin A, Thapa SS, Gioe BW, Grove A. Microbiol. Mol. Biol. Rev. 83 (2019)
  12. The Mechanism of Bacterial Resistance and Potential Bacteriostatic Strategies. Zhang F, Cheng W. Antibiotics (Basel) 11 1215 (2022)
  13. The evolution of MarR family transcription factors as counter-silencers in regulatory networks. Will WR, Fang FC. Curr Opin Microbiol 55 1-8 (2020)
  14. An Update on the Therapeutic Potential of Antimicrobial Peptides against Acinetobacter baumannii Infections. Rangel K, Lechuga GC, Provance DW, Morel CM, De Simone SG. Pharmaceuticals (Basel) 16 1281 (2023)
  15. Bacterial Transcriptional Regulators: A Road Map for Functional, Structural, and Biophysical Characterization. Pis Diez CM, Juncos MJ, Villarruel Dujovne M, Capdevila DA. Int J Mol Sci 23 2179 (2022)
  16. Enhanced Antimicrobial Activity through Synergistic Effects of Cold Atmospheric Plasma and Plant Secondary Metabolites: Opportunities and Challenges. Prasad K, Sasi S, Weerasinghe J, Levchenko I, Bazaka K. Molecules 28 7481 (2023)
  17. MarR Family Transcriptional Regulators and Their Roles in Plant-Interacting Bacteria. Nazaret F, Alloing G, Mandon K, Frendo P. Microorganisms 11 1936 (2023)

Articles citing this publication (64)

  1. Genomic Analysis of the Emergence and Rapid Global Dissemination of the Clonal Group 258 Klebsiella pneumoniae Pandemic. Bowers JR, Kitchel B, Driebe EM, MacCannell DR, Roe C, Lemmer D, de Man T, Rasheed JK, Engelthaler DM, Keim P, Limbago BM. PLoS ONE 10 e0133727 (2015)
  2. Copper is an endogenous modulator of neural circuit spontaneous activity. Dodani SC, Firl A, Chan J, Nam CI, Aron AT, Onak CS, Ramos-Torres KM, Paek J, Webster CM, Feller MB, Chang CJ. Proc. Natl. Acad. Sci. U.S.A. 111 16280-16285 (2014)
  3. Peptidoglycan recognition proteins kill bacteria by inducing oxidative, thiol, and metal stress. Kashyap DR, Rompca A, Gaballa A, Helmann JD, Chan J, Chang CJ, Hozo I, Gupta D, Dziarski R. PLoS Pathog. 10 e1004280 (2014)
  4. Ligand-binding pocket bridges DNA-binding and dimerization domains of the urate-responsive MarR homologue MftR from Burkholderia thailandensis. Gupta A, Grove A. Biochemistry 53 4368-4380 (2014)
  5. The activity of CouR, a MarR family transcriptional regulator, is modulated through a novel molecular mechanism. Otani H, Stogios PJ, Xu X, Nocek B, Li SN, Savchenko A, Eltis LD. Nucleic Acids Res. 44 595-607 (2016)
  6. Aromatic inhibitors derived from ammonia-pretreated lignocellulose hinder bacterial ethanologenesis by activating regulatory circuits controlling inhibitor efflux and detoxification. Keating DH, Zhang Y, Ong IM, McIlwain S, Morales EH, Grass JA, Tremaine M, Bothfeld W, Higbee A, Ulbrich A, Balloon AJ, Westphall MS, Aldrich J, Lipton MS, Kim J, Moskvin OV, Bukhman YV, Coon JJ, Kiley PJ, Bates DM, Landick R. Front Microbiol 5 402 (2014)
  7. Heavy Metal Induced Antibiotic Resistance in Bacterium LSJC7. Chen S, Li X, Sun G, Zhang Y, Su J, Ye J. Int J Mol Sci 16 23390-23404 (2015)
  8. Species-specific activity of antibacterial drug combinations. Brochado AR, Telzerow A, Bobonis J, Banzhaf M, Mateus A, Selkrig J, Huth E, Bassler S, Zamarreño Beas J, Zietek M, Ng N, Foerster S, Ezraty B, Py B, Barras F, Savitski MM, Bork P, Göttig S, Typas A. Nature 559 259-263 (2018)
  9. Permanent draft genome sequence of Bacillus flexus strain T6186-2, a multidrug-resistant bacterium isolated from a deep-subsurface oil reservoir. Zhang F, Jiang X, Chai L, She Y, Yu G, Shu F, Wang Z, Su S, Wenqiong W, Tingsheng X, Zhang Z, Hou D, Zheng B. Mar Genomics 18 Pt B 135-137 (2014)
  10. The Bacillus subtilis tyrZ gene encodes a highly selective tyrosyl-tRNA synthetase and is regulated by a MarR regulator and T box riboswitch. Williams-Wagner RN, Grundy FJ, Raina M, Ibba M, Henkin TM. J. Bacteriol. 197 1624-1631 (2015)
  11. Allosteric histidine switch for regulation of intracellular zinc(II) fluctuation. Zhu R, Song Y, Liu H, Yang Y, Wang S, Yi C, Chen PR. Proc. Natl. Acad. Sci. U.S.A. 114 13661-13666 (2017)
  12. CosR Is a Global Regulator of the Osmotic Stress Response with Widespread Distribution among Bacteria. Gregory GJ, Morreale DP, Boyd EF. Appl Environ Microbiol 86 e00120-20 (2020)
  13. Customized Regulation of Diverse Stress Response Genes by the Multiple Antibiotic Resistance Activator MarA. Rossi NA, Dunlop MJ. PLoS Comput. Biol. 13 e1005310 (2017)
  14. Structural characterization of the DNA-binding mechanism underlying the copper(II)-sensing MarR transcriptional regulator. Zhu R, Hao Z, Lou H, Song Y, Zhao J, Chen Y, Zhu J, Chen PR. J. Biol. Inorg. Chem. 22 685-693 (2017)
  15. Bacterial persistence induced by salicylate via reactive oxygen species. Wang T, El Meouche I, Dunlop MJ. Sci Rep 7 43839 (2017)
  16. Copper-finger protein of Sp1: the molecular basis of copper sensing. Yuan S, Chen S, Xi Z, Liu Y. Metallomics 9 1169-1175 (2017)
  17. Whole genome sequence and comparative genomic analysis of multidrug-resistant Staphylococcus capitis subsp. urealyticus strain LNZR-1. Li X, Lei M, Song Y, Gong K, Li L, Liang H, Jiang X. Gut Pathog 6 45 (2014)
  18. Antagonistic autoregulation speeds up a homogeneous response in Escherichia coli. Rodrigo G, Bajic D, Elola I, Poyatos JF. Sci Rep 6 36196 (2016)
  19. Multidrug resistance operon emrAB contributes for chromate and ampicillin co-resistance in a Staphylococcus strain isolated from refinery polluted river bank. Zhang H, Ma Y, Liu P, Li X. Springerplus 5 1648 (2016)
  20. Transcriptional regulation of the iac locus from Acinetobacter baumannii by the phytohormone indole-3-acetic acid. Shu HY, Lin LC, Lin TK, Chen HP, Yang HH, Peng KC, Lin GH. Antonie Van Leeuwenhoek 107 1237-1247 (2015)
  21. Multipath colourimetric assay for copper(II) ions utilizing MarR functionalized gold nanoparticles. Wang Y, Wang L, Su Z, Xue J, Dong J, Zhang C, Hua X, Wang M, Liu F. Sci Rep 7 41557 (2017)
  22. Research Support, Non-U.S. Gov't Regulating cellular stress responses: an emerging strategy for rational metallodrug design. Yang X. Future Med Chem 10 611-614 (2018)
  23. Small colony variants are more susceptible to copper-mediated contact killing for Pseudomonas aeruginosa and Staphylococcus aureus. Liu S, Zhang XX. J. Med. Microbiol. 65 1143-1151 (2016)
  24. Copper-Promoted Functionalization of Organic Molecules: from Biologically Relevant Cu/O2 Model Systems to Organometallic Transformations. Trammell R, Rajabimoghadam K, Garcia-Bosch I. Chem. Rev. 119 2954-3031 (2019)
  25. Inactivation of MarR gene homologs increases susceptibility to antimicrobials in Bacteroides fragilis. Silva CMG, Silva DNDS, Costa SBD, Almeida JSS, Boente RF, Teixeira FL, Domingues RMCP, Lobo LA. Braz. J. Microbiol. 49 200-206 (2018)
  26. Multi-drug resistant Enterobacter bugandensis species isolated from the International Space Station and comparative genomic analyses with human pathogenic strains. Singh NK, Bezdan D, Checinska Sielaff A, Wheeler K, Mason CE, Venkateswaran K. BMC Microbiol. 18 175 (2018)
  27. Sulfane Sulfur Is a Strong Inducer of the Multiple Antibiotic Resistance Regulator MarR in Escherichia coli. Xu H, Xuan G, Liu H, Xia Y, Xun L. Antioxidants (Basel) 10 1778 (2021)
  28. Sulfane Sulfur Is an Intrinsic Signal for the Organic Peroxide Sensor OhrR of Pseudomonas aeruginosa. Xu H, Xuan G, Liu H, Liu H, Xia Y, Xun L. Antioxidants (Basel) 11 1667 (2022)
  29. The Evolution of SlyA/RovA Transcription Factors from Repressors to Countersilencers in Enterobacteriaceae. Will WR, Brzovic P, Le Trong I, Stenkamp RE, Lawrenz MB, Karlinsey JE, Navarre WW, Main-Hester K, Miller VL, Libby SJ, Fang FC. MBio 10 (2019)
  30. Psychrobacter Phage Encoding an Antibiotics Resistance Gene Represents a Novel Caudoviral Family. Wang H, Ren L, Liang Y, Zheng K, Guo R, Liu Y, Wang Z, Han Y, Zhang X, Shao H, Sung YY, Mok WJ, Wong LL, McMinn A, Wang M. Microbiol Spectr 11 e0533522 (2023)
  31. A novel Escherichia coli cell-based bioreporter for quantification of salicylic acid in cosmetics. Kim Y, Jeon Y, Jang G, Kim BG, Yoon Y. Appl Microbiol Biotechnol 108 148 (2024)
  32. Active degradation of MarA controls coordination of its downstream targets. Rossi NA, Mora T, Walczak AM, Dunlop MJ. PLoS Comput. Biol. 14 e1006634 (2018)
  33. An EmrB multidrug efflux pump in Burkholderia thailandensis with unexpected roles in antibiotic resistance. Sabrin A, Gioe BW, Gupta A, Grove A. J. Biol. Chem. 294 1891-1903 (2019)
  34. Biophysical and Biochemical Characterization of the Binding of the MarR-like Transcriptional Regulator Saro_0803 to the nov1 Promotor and Its Inhibition by Resveratrol. He Z, Ke Z, Wang W, Liu Y, Zhang H, Li Y. Biomolecules 13 541 (2023)
  35. Chemoproteomics of an Indole-Based Quinone Epoxide Identifies Druggable Vulnerabilities in Vancomycin-Resistant Staphylococcus aureus. Kulkarni A, Soni I, Kelkar DS, Dharmaraja AT, Sankar RK, Beniwal G, Rajendran A, Tamhankar S, Chopra S, Kamat SS, Chakrapani H. J. Med. Chem. 62 6785-6795 (2019)
  36. Chiral Upconversion Heterodimers for Quantitative Analysis and Bioimaging of Antibiotic-Resistant Bacteria In Vivo. Sun M, Qu A, Hao C, Wu X, Xu L, Xu C, Kuang H. Adv. Mater. Weinheim 30 e1804241 (2018)
  37. Combining CRISPRi and metabolomics for functional annotation of compound libraries. Anglada-Girotto M, Handschin G, Ortmayr K, Campos AI, Gillet L, Manfredi P, Mulholland CV, Berney M, Jenal U, Picotti P, Zampieri M. Nat Chem Biol 18 482-491 (2022)
  38. Copper (II) binding of NAD(P)H- flavin oxidoreductase (NfoR) enhances its Cr (VI)-reducing ability. Han H, Ling Z, Zhou T, Xu R, He Y, Liu P, Li X. Sci Rep 7 15481 (2017)
  39. Copper Influences the Antibacterial Outcomes of a β-Lactamase-Activated Prochelator against Drug-Resistant Bacteria. Zaengle-Barone JM, Jackson AC, Besse DM, Becken B, Arshad M, Seed PC, Franz KJ. ACS Infect Dis 4 1019-1029 (2018)
  40. Copper and nanostructured anatase rutile and carbon coatings induce adaptive antibiotic resistance. Wasa A, Aitken J, Jun H, Bishop C, Krumdieck S, Godsoe W, Heinemann JA. AMB Express 12 117 (2022)
  41. Deconstructing a multiple antibiotic resistance regulation through the quantification of its input function. Rodrigo G, Bajić D, Elola I, Poyatos JF. NPJ Syst Biol Appl 3 30 (2017)
  42. Deletion of BmoR affects the expression of genes related to thiol/disulfide balance in Bacteroides fragilis. Teixeira FL, Pauer H, Costa SB, Smith CJ, Domingues RMCP, Rocha ER, Lobo LA. Sci Rep 8 14405 (2018)
  43. Draft Genome Sequence of Algoriphagus sp. Strain NH1, a Multidrug-Resistant Bacterium Isolated from Coastal Sediments of the Northern Yellow Sea in China. Mu D, Zhao J, Wang Z, Chen G, Du Z. Genome Announc 4 (2016)
  44. Dynamic context-dependent regulation of auxin feedback signaling in synthetic gene circuits. Avdovic M, Garcia-Navarrete M, Ruiz-Sanchis D, Wabnik K. Proc Natl Acad Sci U S A 120 e2309007120 (2023)
  45. Effects of sub-lethal concentrations of copper ammonium acetate, pyrethrins and atrazine on the response of Escherichia coli to antibiotics. Jun H, Kurenbach B, Aitken J, Wasa A, Remus-Emsermann MNP, Godsoe W, Heinemann JA. F1000Res 8 32 (2019)
  46. EpsRAc is a copper-sensing MarR family transcriptional repressor from Acidithiobacillus caldus. Yin Y, Tong Y, Yang H, Feng S. Appl Microbiol Biotechnol 106 3679-3689 (2022)
  47. Exploring the Tunability and Dynamic Properties of MarR-PmarO Sensor System in Escherichia coli. Zou Y, Li C, Zhang R, Jiang T, Liu N, Wang J, Wang X, Yan Y. ACS Synth Biol 10 2076-2086 (2021)
  48. Genetically encoded formaldehyde sensors inspired by a protein intra-helical crosslinking reaction. Zhu R, Zhang G, Jing M, Han Y, Li J, Zhao J, Li Y, Chen PR. Nat Commun 12 581 (2021)
  49. In vivo biosensors: mechanisms, development, and applications. Shi S, Ang EL, Zhao H. J. Ind. Microbiol. Biotechnol. 45 491-516 (2018)
  50. MarR-Family Transcription Factor HpaR Controls Expression of the vgrR-vgrS Operon of Xanthomonas campestris pv. campestris. Pan Y, Liang F, Li RJ, Qian W. Mol. Plant Microbe Interact. 31 299-310 (2018)
  51. Metal-dependent allosteric activation and inhibition on the same molecular scaffold: the copper sensor CopY from Streptococcus pneumoniae. Glauninger H, Zhang Y, Higgins KA, Jacobs AD, Martin JE, Fu Y, Coyne Rd HJ, Bruce KE, Maroney MJ, Clemmer DE, Capdevila DA, Giedroc DP. Chem Sci 9 105-118 (2018)
  52. Multidrug Resistance Regulators MarA, SoxS, Rob, and RamA Repress Flagellar Gene Expression and Motility in Salmonella enterica Serovar Typhimurium. Thota SS, Chubiz LM. J. Bacteriol. 201 (2019)
  53. Ohr and OhrR Are Critical for Organic Peroxide Resistance and Symbiosis in Azorhizobium caulinodans ORS571. Si Y, Guo D, Deng S, Lu X, Zhu J, Rao B, Cao Y, Jiang G, Yu D, Zhong Z, Zhu J. Genes (Basel) 11 (2020)
  54. Regulation of DNA-binding activity of the Staphylococcus aureus catabolite control protein A by copper (II)-mediated oxidation. Liao X, Li H, Guo Y, Yang F, Chen Y, He X, Li H, Xia W, Mao ZW, Sun H. J Biol Chem 298 101587 (2022)
  55. Stapled endosome disrupting alginate particles for cytosolic delivery of cations. Acharya AP, Little SR. J Drug Target 23 690-697 (2015)
  56. Structural basis of transcriptional regulation by CouR, a repressor of coumarate catabolism, in Rhodopseudomonas palustris. Cogan DP, Baraquet C, Harwood CS, Nair SK. J. Biol. Chem. 293 11727-11735 (2018)
  57. Synchronization of gene expression across eukaryotic communities through chemical rhythms. Pérez-García S, García-Navarrete M, Ruiz-Sanchis D, Prieto-Navarro C, Avdovic M, Pucciariello O, Wabnik K. Nat Commun 12 4017 (2021)
  58. The Atypical Antipsychotic Quetiapine Promotes Multiple Antibiotic Resistance in Escherichia coli. Kyono Y, Ellezian L, Hu Y, Eliadis K, Moy J, Hirsch EB, Federle MJ, Flowers SA. J Bacteriol 204 e0010222 (2022)
  59. The Escherichia coli MarA protein regulates the ycgZ-ymgABC operon to inhibit biofilm formation. Kettles RA, Tschowri N, Lyons KJ, Sharma P, Hengge R, Webber MA, Grainger DC. Mol. Microbiol. 112 1609-1625 (2019)
  60. The MarR family regulator OsbR controls oxidative stress response, anaerobic nitrate respiration, and biofilm formation in Chromobacterium violaceum. Alves JA, Previato-Mello M, Barroso KCM, Koide T, da Silva Neto JF. BMC Microbiol 21 304 (2021)
  61. The copper-linked Escherichia coli AZY operon: Structure, metal binding, and a possible physiological role in copper delivery. Hadley RC, Zhitnitsky D, Livnat-Levanon N, Masrati G, Vigonsky E, Rose J, Ben-Tal N, Rosenzweig AC, Lewinson O. J Biol Chem 298 101445 (2022)
  62. Tuning site-specific dynamics to drive allosteric activation in a pneumococcal zinc uptake regulator. Capdevila DA, Huerta F, Edmonds KA, Le MT, Wu H, Giedroc DP. Elife 7 (2018)
  63. Using Selection by Nonantibiotic Stressors to Sensitize Bacteria to Antibiotics. Maltas J, Krasnick B, Wood KB. Mol Biol Evol 37 1394-1406 (2020)
  64. Zinc-mediated conformational preselection mechanism in the allosteric control of DNA binding to the zinc transcriptional regulator (ZitR). He X, Ni D, Zhang H, Li X, Zhang J, Fu Q, Liu Y, Lu S. Sci Rep 10 13276 (2020)


Quick links