1932

Abstract

Infections caused by bacteria are a leading cause of death worldwide. Although antibiotics remain a key clinical therapy, their effectiveness has been severely compromised by the development of drug resistance in bacterial pathogens. Multidrug efflux transporters—a common and powerful resistance mechanism—are capable of extruding a number of structurally unrelated antimicrobials from the bacterial cell, including antibiotics and toxic heavy metal ions, facilitating their survival in noxious environments. Transporters of the resistance-nodulation-cell division (RND) superfamily typically assemble as tripartite efflux complexes spanning the inner and outer membranes of the cell envelope. In , the CusCFBA complex, which mediates resistance to copper(I) and silver(I) ions, is the only known RND transporter specific to heavy metals. Here, we describe the current knowledge of individual pump components of the Cus system, a paradigm for efflux machinery, and speculate on how RND pumps assemble to fight diverse antimicrobials.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-biophys-051013-022855
2014-05-06
2024-06-17
Loading full text...

Full text loading...

/deliver/fulltext/biophys/43/1/annurev-biophys-051013-022855.html?itemId=/content/journals/10.1146/annurev-biophys-051013-022855&mimeType=html&fmt=ahah

Literature Cited

  1. Aires JR, Nikaido H. 1.  2005. Aminoglycosides are captured from both periplasm and cytoplasm by the AcrD multidrug efflux transporter of Escherichia coli. J. Bacteriol. 187:61923–29 [Google Scholar]
  2. Akama H, Kanemaki M, Yoshimura M, Tsukihara T, Kashiwagi T. 2.  et al. 2004. Crystal structure of the drug discharge outer membrane protein, OprM, of Pseudomonas aeruginosa: dual modes of membrane anchoring and occluded cavity end. J. Biol. Chem. 279:5152816–19 [Google Scholar]
  3. Akama H, Matsuura T, Kashiwagi S, Yoneyama H, Narita S. 3.  et al. 2004. Crystal structure of the membrane fusion protein, MexA, of the multidrug transporter in Pseudomonas aeruginosa. J. Biol. Chem. 279:2525939–42 [Google Scholar]
  4. Angus BL, Carey AM, Caron DA, Kropinski AM, Hancock RE. 4.  1982. Outer membrane permeability in Pseudomonas aeruginosa: comparison of a wild-type with an antibiotic-supersusceptible mutant. Antimicrob. Agents Chemother. 21:2299–309 [Google Scholar]
  5. Arnesano F, Banci L, Bertini I, Huffman DL, O'Halloran TV. 5.  2001. Solution structure of the Cu(I) and apo forms of the yeast metallochaperone, Atx1. Biochemistry 40:61528–39 [Google Scholar]
  6. Arnesano F, Banci L, Bertini I, Mangani S, Thompsett AR. 6.  2003. A redox switch in CopC: an intriguing copper trafficking protein that binds copper(I) and copper(II) at different sites. Proc. Natl. Acad. Sci. USA 100:73814–19 [Google Scholar]
  7. Atilgan AR, Durell SR, Jernigan RL, Demirel MC, Keskin O. 7.  et al. 2001. Anisotropy of fluctuation dynamics of proteins with an elastic network model. Biophys. J. 80:1505–15 [Google Scholar]
  8. Bagai I, Liu W, Rensing C, Blackburn NJ, McEvoy MM. 8.  2007. Substrate-linked conformational change in the periplasmic component of a Cu(I)/Ag(I) efflux system. J. Biol. Chem. 282:4935695–702 [Google Scholar]
  9. Bagai I, Rensing C, Blackburn NJ, McEvoy MM. 9.  2008. Direct metal transfer between periplasmic proteins identifies a bacterial copper chaperone. Biochemistry 47:4411408–14 [Google Scholar]
  10. Baranova N, Nikaido H. 10.  2002. The baeSR two-component regulatory system activates transcription of the yegMNOB (mdtABCD) transporter gene cluster in Escherichia coli and increases its resistance to novobiocin and deoxycholate. J. Bacteriol. 184:154168–76 [Google Scholar]
  11. Blattner FR, Plunkett G III, Bloch CA, Perna NT, Burland V. 11.  et al. 1997. The complete genome sequence of Escherichia coli K-12. Science 277:1453–62 [Google Scholar]
  12. Bohnert JA, Schuster S, Fähnrich E, Trittler R, Kern WV. 12.  2007. Altered spectrum of multidrug resistance associated with a single point mutation in the Escherichia coli RND-type MDR efflux pump YhiV (MdtF). J. Antimicrob. Chemother. 59:61216–22 [Google Scholar]
  13. Brown MH, Paulsen IT, Skurray RA. 13.  1999. The multidrug efflux protein NorM is a prototype of a new family of transporters. Mol. Microbiol. 31:394–95 [Google Scholar]
  14. Brown NL, Rouch DA, Lee BTO. 14.  1992. Copper resistance determinants in bacteria. Plasmid 27:41–51 [Google Scholar]
  15. Cha J-S, Cooksey DA. 15.  1991. Copper resistance in Pseudomonas syringae mediated by periplasmic and outer membrane proteins. Proc. Natl. Acad. Sci. USA 88:8915–19 [Google Scholar]
  16. Chakravorty DK, Wang B, Ucisik MN, Merz KM Jr. 16.  2011. Insight into the cation-π interaction at the metal binding site of the copper metallochaperone. J. Am. Chem. Soc. 133:48199330–33 [Google Scholar]
  17. Changela A, Chen K, Xue Y, Holschen J, Outten CE. 17.  et al. 2003. Molecular basis of metal-ion selectivity and zeptomolar sensitivity by CueR. Science 301:56381383–87 [Google Scholar]
  18. Chopra I. 18.  2007. The increasing use of silver-based products as antimicrobial agents: a useful development or a cause for concern?. J. Antimicrob. Chemother. 59:587–90 [Google Scholar]
  19. Conroy O, Kim E-H, McEvoy MM, Rensing C. 19.  2010. Differing ability to transport non-metal substrates by two RND-type metal exporters. FEMS Microbiol. Lett. 308:2115–22 [Google Scholar]
  20. Courvalin P. 20.  1994. Transfer of antibiotic resistance genes between gram-positive and gram-negative bacteria. Antimicrob. Agents Chemother. 38:1447–51 [Google Scholar]
  21. Das D, Xu QS, Lee JY, Ankoudinova I, Huang C. 21.  et al. 2007. Crystal structure of the multidrug efflux transporter AcrB at 3.1 Å resolution reveals the N-terminal region with conserved amino acids. J. Struct. Biol. 158:3494–502 [Google Scholar]
  22. Delmar JA, Su C-C, Yu EW. 22.  2013. Structural mechanisms of heavy-metal extrusion by the Cus efflux system. Biometals 26:4593–607 [Google Scholar]
  23. Eicher T, Cha HJ, Seeger MA, Brandstätter L, El-Delik J. 23.  et al. 2012. Transport of drugs by the multidrug transporter AcrB involves an access and a deep binding pocket that are separated by a switch-loop. Proc. Natl. Acad. Sci. USA 109:155687–92 [Google Scholar]
  24. Festa RA, Thiele DJ. 24.  2011. Copper: an essential metal in biology. Curr. Biol. 21:21R877–83 [Google Scholar]
  25. Franke S, Grass G, Nies DH. 25.  2001. The product of the ybdE gene of the Escherichia coli chromosome is involved in detoxification of silver ions. Microbiology 147:965–72 [Google Scholar]
  26. Franke S, Grass G, Rensing C, Nies DH. 26.  2003. Molecular analysis of the copper-transporting efflux system CusCFBA of Escherichia coli. J. Bacteriol. 185:133804–12 [Google Scholar]
  27. Goldberg M, Pribyl T, Juhnke S, Nies DH. 27.  1999. Energetics and topology of CzcA, a cation/proton antiporter of the resistance-nodulation-cell division protein family. J. Biol. Chem. 273:3726065–70 [Google Scholar]
  28. Grass G, Rensing C. 28.  2001. Genes involved in copper homeostasis in Escherichia coli. J. Bacteriol. 183:62145–47 [Google Scholar]
  29. Grass G, Rensing C, Solioz M. 29.  2011. Metallic copper as an antimicrobial surface. Appl. Environ. Microbiol. 77:51541–47 [Google Scholar]
  30. Gu R, Su C-C, Shi F, Li M, McDermott G. 30.  et al. 2007. Crystal structure of the transcriptional regulator CmeR from Campylobacter jejuni. J. Mol. Biol. 372:3583–93 [Google Scholar]
  31. Gudipaty SA, Larsen AS, Rensing C, McEvoy MM. 31.  2012. Regulation of Cu(I)/Ag(I) efflux genes in Escherichia coli by the sensor kinase CusS. FEMS Microbiol. Lett. 330:30–37 [Google Scholar]
  32. Gupta A, Matsui K, Lo J-F, Silver S. 32.  1999. Molecular basis for resistance to silver cations in Salmonella. Nat. Med. 5:2183–88 [Google Scholar]
  33. Gupta A, Phung LT, Taylor DE, Silver S. 33.  2001. Diversity of silver resistance genes in IncH incompatibility group plasmids. Microbiology 147:3393–402 [Google Scholar]
  34. Haber F, Weiss J. 34.  1932. On the catalysis of hydroperoxides. Naturwissenschaften 20:51948–50 [Google Scholar]
  35. Hagman KE, Shafer WM. 35.  1995. Transcriptional control of the mtr efflux system of Neisseria gonorrhoeae. J. Bacteriol. 177:144162–65 [Google Scholar]
  36. Henderson PJ. 36.  1993. The 12-transmembrane helix transporters. Curr. Opin. Cell Biol. 5:4708–21 [Google Scholar]
  37. Higgins CF. 37.  2007. Multiple molecular mechanisms for multidrug resistance transporters. Nature 446:749–57 [Google Scholar]
  38. Higgins MK, Bokma E, Koronakis E, Hughes C, Koronakis V. 38.  2004. Structure of the periplasmic component of a bacterial drug efflux pump. Proc. Natl. Acad. Sci. USA 101:279995–99 [Google Scholar]
  39. Hinchliffe P, Symmons MF, Hughes C, Koronakis V. 39.  2013. Structure and operation of bacterial tripartite pumps. Annu. Rev. Microbiol. 67:221–42 [Google Scholar]
  40. Hoffmann KM, Williams D, Shafer WM, Brennan RG. 40.  2005. Characterization of the multiple transferable resistance repressor MtrR, from Neisseria gonorrhoea. J. Bacteriol. 187:145008–12 [Google Scholar]
  41. Hooper DC. 41.  1999. Mechanisms of fluoroquinolone resistance. Drug Resist. Update 2:38–55 [Google Scholar]
  42. Jaffé A, Chabbert YA, Derlot E. 42.  1983. Selection and characterization of β-lactam-resistant Escherichia coli K-12 mutants. Antimicrob. Agents Chemother. 23:4622–25 [Google Scholar]
  43. Janganan TK, Bavro VN, Zhang L, Matak-Vinkovic D, Barrera NP. 43.  et al. 2011. Evidence for the assembly of a bacterial tripartite multidrug pump with a stoichiometry of 3:6:3. J. Biol. Chem. 286:3026900–12 [Google Scholar]
  44. Janganan TK, Zhang L, Bavro VN, Matak-Vinkovic D, Barrera NP. 44.  et al. 2011. Opening of the outer membrane protein channel in tripartite efflux pumps is induced by interaction with the membrane fusion partner. J. Biol. Chem. 286:75484–93 [Google Scholar]
  45. Jiang J, Nadas IA, Kim MA, Franz KJ. 45.  2005. A Mets motif peptide found in copper transport proteins selectively binds Cu(I) with methionine-only coordination. Inorg. Chem. 44:269787–94 [Google Scholar]
  46. Kim E-H, Nies DH, McEvoy MM, Rensing C. 46.  2011. Switch or funnel: how RND-type transport systems control periplasmic metal homeostasis. J. Bacteriol. 193:102381–87 [Google Scholar]
  47. Kim HS, Nikaido H. 47.  2012. Different function of MdtB and MdtC subunits in the heterotrimeric efflux transporter MdtB2C complex of Escherichia coli. Biochemistry 51:204188–97 [Google Scholar]
  48. Kittleson JT, Loftin IR, Hausrath AC, Engelhardt KP, Rensing C, McEvoy MM. 48.  2006. Periplasmic metal-resistance protein CusF exhibits high affinity and specificity for both CuI and AgI. Biochemistry 45:3711096–102 [Google Scholar]
  49. Kobayashi N, Nishino K, Yamaguchi A. 49.  2001. Novel macrolide-specific ABC-type efflux transporter in Escherichia coli. J. Bacteriol. 183:195639–44 [Google Scholar]
  50. Koronakis V, Sharff A, Koronakis E, Luisi B, Hughes C. 50.  2000. Crystal structure of the bacterial membrane protein TolC central to multidrug efflux and protein export. Nature 405:914–19 [Google Scholar]
  51. Kulathila R, Kulathila R, Indic M, van den Berg B. 51.  2011. Crystal structure of Escherichia coli CusC, the outer membrane component of a heavy metal efflux pump. PLoS ONE 6:1e15610 [Google Scholar]
  52. Lane TW, Saito MA, George GN, Pickering IJ, Prince RC. 52.  et al. 2005. Biochemistry: a cadmium enzyme from a marine diatom. Nature 435:42 [Google Scholar]
  53. Lau SY, Zgurskaya HI. 53.  2005. Cell division defects in Escherichia coli deficient in the multidrug efflux transporter AcrEF-TolC. J. Bacteriol. 187:227815–25 [Google Scholar]
  54. Levy SB. 54.  1992. Active efflux mechanisms for antimicrobial resistance. Antimicrob. Agents Chemother. 36:4695–703 [Google Scholar]
  55. Li XZ, Nikaido H. 55.  2004. Efflux-mediated drug resistance in bacteria. Drugs 64:2159–204 [Google Scholar]
  56. Lin J, Akiba M, Sahin O, Zhang Q. 56.  2005. CmeR functions as a transcriptional repressor for the multidrug efflux pump CmeABC in Campylobacter jejuni. Antimicrob. Agents Chemother. 49:31067–75 [Google Scholar]
  57. Lin J, Michel LO, Zhang Q. 57.  2002. CmeABC functions as a multidrug efflux system in Campylobacter jejuni. Antimicrob. Agents Chemother. 46:72124–31 [Google Scholar]
  58. Loftin IR, Franke S, Blackburn NJ, McEvoy MM. 58.  2007. Unusual Cu(I)/Ag(I) coordination of Escherichia coli CusF as revealed by atomic resolution crystallography and X-ray absorption spectroscopy. Prot. Sci. 16:2287–93 [Google Scholar]
  59. Loftin IR, Franke S, Roberts SA, Weichsel A, Héroux A. 59.  et al. 2005. A novel copper-binding fold for the periplasmic copper resistance protein CusF. Biochemistry 44:3110533–40 [Google Scholar]
  60. Loftin IR, McEvoy MM. 60.  2009. Tryptophan Cu(I)-π interaction fine-tunes the metal binding properties of the bacterial metallochaperone CusF. J. Biol. Inorg. Chem. 14:6905–12 [Google Scholar]
  61. Long F, Su C-C, Lei H-T, Bolla JR, Do SV, Yu EW. 61.  2012. Structure and mechanism of the tripartite CusCBA heavy-metal efflux complex. Phil. Trans. R. Soc. B 367:1047–58 [Google Scholar]
  62. Long F, Su C-C, Zimmermann MT, Boyken SE, Rajashankar KR. 62.  et al. 2010. Crystal structures of the CusA efflux pump suggest methionine-mediated metal transport. Nature 467:7314484–88 [Google Scholar]
  63. Ma D, Cook DN, Alberti M, Pon NG, Nikaido H. 63.  et al. 1993. Molecular cloning and characterization of acrA and acrE genes of Escherichia coli. J. Bacteriol. 175:196299–313 [Google Scholar]
  64. Macomber L, Imlay JA. 64.  2009. The iron-sulfur clusters of dehydratases are primary intracellular targets of copper toxicity. Proc. Natl. Acad. Sci. USA 106:208344–49 [Google Scholar]
  65. McHugh GL, Moellering RC, Hopkins CC, Swartz MN. 65.  1975. Salmonella typhimurium resistant to silver nitrate, chloramphenicol, and ampicillin. Lancet 305:7901235–40 [Google Scholar]
  66. Mealman TD, Zhou M, Affandi T, Chacón KN, Aranguren ME. 66.  et al. 2012. N-terminal region of CusB is sufficient for metal binding and metal transfer with the metallochaperone CusF. Biochemistry 51:6767–75 [Google Scholar]
  67. Mikolosko J, Bobyk K, Zgurskaya HI, Ghosh P. 67.  2006. Conformational flexibility in the multidrug efflux system protein AcrA. Structure 14:3577–87 [Google Scholar]
  68. Munson GP, Lam DL, Outten FW, O'Halloran TV. 68.  2000. Identification of a copper-responsive two-component system on the chromosome of Escherichia coli K-12. J. Bacteriol. 182:205864–71 [Google Scholar]
  69. Murakami S. 69.  2008. Multidrug efflux transporter, AcrB—the pumping mechanism. Curr. Opin. Struct. Biol. 18:459–65 [Google Scholar]
  70. Murakami S, Nakashima R, Yamashita E, Matsumoto T, Yamaguchi A. 70.  2006. Crystal structures of a multidrug transporter reveal a functionally rotating mechanism. Nature 443:173–79 [Google Scholar]
  71. Murakami S, Nakashima R, Yamashita E, Yamaguchi A. 71.  2002. Crystal structure of bacterial multidrug efflux transporter AcrB. Nature 419:587–93 [Google Scholar]
  72. Nagakubo S, Nishino K, Hirata T, Yamaguchi A. 72.  2002. The putative response regulator BaeR stimulates multidrug resistance of Escherichia coli via a novel multidrug exporter system, MdtABC. J. Bacteriol. 184:154161–67 [Google Scholar]
  73. Nies DH. 73.  1995. The cobalt, zinc, and cadmium efflux system CzcABC from Alcaligenes eutrophus functions as a cation-proton antiporter in Escherichia coli. J. Bacteriol. 177:102707–12 [Google Scholar]
  74. Nies DH. 74.  1999. Microbial heavy-metal resistance. Appl. Microbiol. Biotechnol. 51:730–50 [Google Scholar]
  75. Nies DH. 75.  2003. Efflux-mediated heavy metal resistance in prokaryotes. FEMS Microbiol. Rev. 27:2313–39 [Google Scholar]
  76. Nies DH. 76.  2007. Bacterial transition metal homeostasis. Molecular Microbiology of Heavy Metals 6 DH Nies, S Silver 117–42 Berlin/Heidelberg: Springer [Google Scholar]
  77. Nies DH. 77.  2013. RND efflux pumps for metal cations. Microbial Efflux Pumps: Current Research 1 EW Yu, Q Zhang, MH Brown 79–121 Norfolk, UK: Caister Academic [Google Scholar]
  78. Nies DH, Nies A, Chu L, Silver S. 78.  1989. Expression and nucleotide sequence of a plasmid-determined divalent cation efflux system from Alcaligenes eutrophus. Proc. Natl. Acad. Sci. USA 86:7351–55 [Google Scholar]
  79. Nikaido H. 79.  1989. Outer membrane barrier as a mechanism of antimicrobial resistance. Antimicrob. Agents Chemother. 33:111831–36 [Google Scholar]
  80. Nikaido H. 80.  1994. Prevention of drug access to bacterial targets: permeability barriers and active efflux. Science 264:382–88 [Google Scholar]
  81. Nikaido H. 81.  1996. Multidrug efflux pumps of gram-negative bacteria. J. Bacteriol. 178:205853–59 [Google Scholar]
  82. Nikaido H. 82.  2011. Structure and mechanism of RND-type multidrug efflux pumps. Adv. Enzymol. Relat. Areas Mol. Biol. 77:1–60 [Google Scholar]
  83. Nikaido H, Takatsuka Y. 83.  2009. Mechanisms of RND multidrug efflux pumps. Biochim. Biophys. Acta 1794:769–81 [Google Scholar]
  84. Nishino K, Yamaguchi A. 84.  2001. Analysis of a complete library of putative drug transporter genes in Escherichia coli. J. Bacteriol. 183:205803–12 [Google Scholar]
  85. Outten FW, Huffman DL, Hale JA, O'Halloran TV. 85.  2001. The independent cue and cus systems confer copper tolerance during aerobic and anaerobic growth in Escherichia coli. J. Biol. Chem. 276:3330670–77 [Google Scholar]
  86. Paulsen IT, Brown MH, Skurray RA. 86.  1996. Proton-dependent multi-drug efflux systems. Microbiol. Rev. 60:4575–608 [Google Scholar]
  87. Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. 87.  2000. Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes. J. Mol. Biol. 301:75–100 [Google Scholar]
  88. Peña MM, Lee J, Thiele DJ. 88.  1999. A delicate balance: homeostatic control of copper uptake and distribution. J. Nutr. 129:71251–60 [Google Scholar]
  89. Percival SL, Bowler PG, Russell D. 89.  2005. Bacterial resistance to silver in wound care. J. Hosp. Infect. 60:1–7 [Google Scholar]
  90. Pos KM. 90.  2009. Drug transport mechanism of the AcrB efflux pump. Biochim. Biophys. Acta 1794:5782–93 [Google Scholar]
  91. Pugsley AP, Schnaitman CA. 91.  1978. Identification of three genes controlling production of new outer membrane pore proteins in Escherichia coli K-12. J. Bacteriol. 135:31118–29 [Google Scholar]
  92. Rensing C, Fan B, Sharma R, Mitra B, Rosen BP. 92.  2000. CopA: an Escherichia coli Cu(I)-translocating P-type ATPase. Proc. Natl. Acad. Sci. USA 97:2652–56 [Google Scholar]
  93. Rensing C, Grass G. 93.  2003. Escherichia coli mechanisms of copper homeostasis in a changing environment. FEMS Microbiol. Rev. 27:197–213 [Google Scholar]
  94. Rensing C, Pribyl T, Nies DH. 94.  1997. New functions for the three subunits of the CzcCBA cation-proton antiporter. J. Bacteriol. 179:6871–79 [Google Scholar]
  95. Roberts SA, Weichsel A, Grass G, Thakali K, Hazzard JT. 95.  et al. 2002. Crystal structure and electron transfer kinetics of CueO, a multicopper oxidase required for copper homeostasis in Escherichia coli. Proc. Natl. Acad. Sci. USA 99:52766–71 [Google Scholar]
  96. Rosenberg EY, Ma D, Nikaido H. 96.  2000. AcrD of Escherichia coli is an aminoglycoside efflux pump. J. Bacteriol. 182:61754–56 [Google Scholar]
  97. Routh MD, Zalucki Y, Su C-C, Long F, Zhang Q. 97.  et al. 2011. Efflux pumps of the resistance-nodulation-division family: a perspective of their structure, function, and regulation in gram-negative bacteria. Advances in Enzymology and Related Areas of Molecular Biology 77 EJ Toone 109–46 Hoboken, NJ: Wiley [Google Scholar]
  98. Russell AD, Hugo WB. 98.  1994. Antimicrobial activity and action of silver. Prog. Med. Chem. 31:351–70 [Google Scholar]
  99. Saier MH Jr. 99.  1994. Computer-aided analyses of transport protein sequences: gleaning evidence concerning function, structure, biogenesis, and evolution. Microbiol. Rev. 58:171–93 [Google Scholar]
  100. Saier MH Jr. 100.  1998. Molecular phylogeny as a basis for the classification of transport proteins from bacteria, archaea and eukarya. Adv. Microb. Physiol. 40:8181–136 [Google Scholar]
  101. Saier MH Jr, Beatty JT, Goffeau A, Harley KT, Heijne WH. 101.  et al. 1999. The major facilitator superfamily. J. Mol. Microbiol. Biotechnol. 1:2257–79 [Google Scholar]
  102. Saier MH Jr, Paulsen IT. 102.  2001. Phylogeny of multidrug transporters. Semin. Cell Dev. Biol. 12:205–13 [Google Scholar]
  103. Seeger MA, Diederichs K, Eicher T, Brandstätter L, Schiefner A. 103.  et al. 2008. The AcrB efflux pump: Conformational cycling and peristalsis lead to multidrug resistance. Curr. Drug Targets 9:9729–49 [Google Scholar]
  104. Seeger MA, Schiefner A, Eicher T, Verrey F, Diederichs K. 104.  et al. 2006. Structural asymmetry of AcrB trimer suggests a peristaltic pump mechanism. Science 313:57911295–98 [Google Scholar]
  105. Sennhauser G, Amstutz P, Briand C, Storchenegger O, Grütter MG. 105.  2007. Drug export pathway of multidrug exporter AcrB revealed by DARPin inhibitors. PLoS ONE 5:1e7 [Google Scholar]
  106. Sennhauser G, Bukowksa MA, Briand C, Grütter MG. 106.  2009.. C rystal structure of the multidrug exporter MexB from Pseudomonas aeruginosa. J. Mol. Biol. 389:134–45 [Google Scholar]
  107. Shafer WM, Qu X-D, Waring AJ, Lehrer RI. 107.  1998. Modulation of the Neisseria gonorrhoeae susceptibility to vertebrate antibacterial peptides due to a member of the resistance/nodulation/division efflux pump family. Proc. Natl. Acad. Sci. USA 95:41829–33 [Google Scholar]
  108. Silver S. 108.  1996. Bacterial heavy metal resistance: new surprises. Annu. Rev. Microbiol. 50:753–89 [Google Scholar]
  109. Silver S. 109.  1996. Bacterial resistances to toxic metal ions—a review. Gene 179:9–19 [Google Scholar]
  110. Silver S. 110.  2003. Bacterial silver resistance: molecular biology and uses and misuses of silver compounds. FEMS Microbiol. Rev. 27:341–53 [Google Scholar]
  111. Silver S, Misra TK. 111.  1988. Plasmid-mediated heavy metal resistances. Annu. Rev. Microbiol. 42:717–43 [Google Scholar]
  112. Silver S, Phung LT, Silver G. 112.  2006. Silver as biocides in burn and wound dressings and bacterial resistance to silver compounds. J. Ind. Microbiol. Biotechnol. 33:627–34 [Google Scholar]
  113. Singh SK, Grass G, Rensing C, Montfort WR. 113.  2004. Cuprous oxidase activity of CueO from Escherichia coli. J. Bacteriol. 186:227815–17 [Google Scholar]
  114. Singh SK, Roberts SA, McDevitt SF, Weichsel A, Wildner GF. 114.  et al. 2011. Crystal structures of multicopper oxidase CueO bound to copper(I) and silver(I): functional role of a methionine-rich sequence. J. Biol. Chem. 286:4337849–57 [Google Scholar]
  115. Stegmeier JF, Polleichtner G, Brandes N, Hotz C, Andersen C. 115.  2006. Importance of the adaptor (membrane fusion) protein hairpin domain for the functionality of multidrug efflux pumps. Biochemistry 45:10303–12 [Google Scholar]
  116. Su C-C, Li M, Gu R, Takatsuka Y, McDermott G. 116.  et al. 2006. Conformation of the AcrB multidrug efflux pump in mutants of the putative proton relay pathway. J. Bacteriol. 188:207290–96 [Google Scholar]
  117. Su C-C, Long F, Lei H-T, Bolla JR, Do SV. 117.  et al. 2012. Charged amino acids (R83, E567, D617, E625, R669, and K678) of CusA are required for metal ion transport in the Cus efflux system. J. Mol. Biol. 422:429–41 [Google Scholar]
  118. Su C-C, Long F, Yu EW. 118.  2011. The Cus efflux system removes toxic ions via a methionine shuttle. Prot. Sci. 20:66–18 [Google Scholar]
  119. Su C-C, Long F, Zimmermann MT, Rajashankar KR, Jernigan RL. 119.  et al. 2011. Crystal structure of the CusBA heavy-metal efflux complex of Escherichia coli. Nature 470:558–63 [Google Scholar]
  120. Su C-C, Yang F, Long F, Reyon D, Routh MD. 120.  et al. 2009. Crystal structure of the membrane fusion protein CusB from Escherichia coli. J. Mol. Biol. 393:2342–55 [Google Scholar]
  121. Symmons MF, Bokma E, Koronakis E, Hughes C, Koronakis V. 121.  2009. The assembled structure of a complete tripartite bacterial multidrug efflux pump. Proc. Natl. Acad. Sci. USA 106:177173–78 [Google Scholar]
  122. Thieme D, Neubauer P, Nies DH, Grass G. 122.  2008. Sandwich hybridization assay for sensitive detection of dynamic changes in mRNA transcript levels in crude Escherichia coli cell extracts in response to copper ions. Appl. Environ. Microbiol. 74:247463–70 [Google Scholar]
  123. Tseng TT, Gratwick KS, Kollman J, Park D, Nies DH. 123.  et al. 1999. The RND permease superfamily: an ancient, ubiquitous and diverse family that includes human disease and development proteins. J. Mol. Microbiol. Biotechnol. 1:1107–25 [Google Scholar]
  124. Van Bambeke F, Balzi E, Tulkens PM. 124.  2000. Antibiotic efflux pumps. Biochem. Pharmacol. 60:457–70 [Google Scholar]
  125. Veal WL, Nicholas RA, Shafer WM. 125.  2002. Overexpression of the MtrC-MtrD-MtrE efflux pump due to an mtrR mutation is required for chromosomally mediated penicillin resistance in Neisseria gonorrhoeae. J. Bacteriol. 184:205619–24 [Google Scholar]
  126. Waldron KJ, Rutherford JC, Ford D, Robinson NJ. 126.  2009. Metalloproteins and metal sensing. Nature 460:823–30 [Google Scholar]
  127. Wells TNC, Scully P, Paravicini G, Proudfoot AEI, Payton MA. 127.  1995. Mechanism of irreversible inactivation of phosphomannose isomerases by silver ions and flamazine. Biochemistry 34:7896–903 [Google Scholar]
  128. Xue Y, Davis AV, Balakrishnan G, Stasser JP, Staehlin BM. 128.  et al. 2008. Cu(I) recognition via cation-π and methionine interactions in CusF. Nat. Chem. Biol. 4:2107–9 [Google Scholar]
  129. Yamamoto K, Ishihama A. 129.  2005. Transcriptional response of Escherichia coli to external copper. Mol. Microbiol. 56:1215–27 [Google Scholar]
  130. Yu EW, Aires JR, McDermott G, Nikaido H. 130.  2005. A periplasmic drug-binding site of the AcrB multidrug efflux pump: a crystallographic and site-directed mutagenesis study. J. Bacteriol. 187:196804–15 [Google Scholar]
  131. Yu EW, McDermott G, Zgurskaya HI, Nikaido H, Koshland DE Jr. 131.  2003. Structural basis of multiple drug-binding capacity of the AcrB multidrug efflux pump. Science 300:976–80 [Google Scholar]
  132. Zgurskaya HI, Nikaido H. 132.  2000. Multidrug resistance mechanisms: drug efflux across two membranes. Mol. Microbiol. 37:2219–25 [Google Scholar]
  133. Zhang L, Koay M, Maher MJ, Xiao Z, Wedd AG. 133.  2006. Intermolecular transfer of copper ions from the CopC protein of Pseudomonas syringae. Crystal structures of fully loaded CuICuII forms. J. Am. Chem. Soc. 128:5834–50 [Google Scholar]
/content/journals/10.1146/annurev-biophys-051013-022855
Loading
/content/journals/10.1146/annurev-biophys-051013-022855
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error