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Efflux-Mediated Antimicrobial Resistance in Bacteria pp 29–44Cite as

Structural and Functional Landscape of MFS and MATE Efflux Pumps

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Abstract

Multidrug transporters play a crucial role in causing drug resistance in infectious microorganisms and tumors. They are integral membrane proteins that exhibit an exceptionally broad specificity for unrelated molecules including antibiotics and anticancer agents. By mediating export of toxic pharmaceuticals from the cell’s interior, multidrug transporters reduce the concentration of these agents in the cell to a level where toxicity is lost. In spite of intense efforts, it is still not clear exactly how multidrug transporters work. In this chapter, we discuss some of the recent advances for multidrug transporters in two important families, the major facilitator superfamily (MFS) and multidrug and toxic compound extrusion (MATE) family.

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References

  1. Putman M, van Veen HW, Konings WN (2000) Molecular properties of bacterial multidrug transporters. Microbiol Mol Biol Rev 64:672–693. doi:10.1128/MMBR.64.4.672-693.2000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Hassan KA, Elbourne LD, Li L, Gamage HK, Liu Q, Jackson SM, Sharples D, Kolsto AB et al (2015) An ace up their sleeve: a transcriptomic approach exposes the AceI efflux protein of Acinetobacter baumannii and reveals the drug efflux potential hidden in many microbial pathogens. Front Microbiol 6:333. doi:10.3389/fmicb.2015.00333

    Article  PubMed  PubMed Central  Google Scholar 

  3. Marger MD, Saier MH Jr (1993) A major superfamily of transmembrane facilitators that catalyse uniport, symport and antiport. Trends Biochem Sci 18:13–20. doi:10.1016/0968-0004(93)90081-W

    Article  CAS  PubMed  Google Scholar 

  4. Pao SS, Paulsen IT, Saier MH Jr (1998) Major facilitator superfamily. Microbiol Mol Biol Rev 62:1–34

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Saier MH Jr, Beatty JT, Goffeau A, Harley KT, Heijne WH, Huang SC, Jack DL, Jahn PS et al (1999) The major facilitator superfamily. J Mol Microbiol Biotechnol 1:257–279

    CAS  PubMed  Google Scholar 

  6. Reddy VS, Shlykov MA, Castillo R, Sun EI, Saier MH Jr (2012) The major facilitator superfamily (MFS) revisited. FEBS J 279:2022–2035. doi:10.1111/j.1742-4658.2012.08588.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Saier MH Jr, Paulsen IT (2001) Phylogeny of multidrug transporters. Semin Cell Dev Biol 12:205–213. doi:10.1006/scdb.2000.0246

    Article  CAS  PubMed  Google Scholar 

  8. Chen DE, Podell S, Sauer JD, Swanson MS, Saier MH Jr (2008) The phagosomal nutrient transporter (Pht) family. Microbiology 154:42–53. doi:10.1099/mic.0.2007/010611-0

    Article  CAS  PubMed  Google Scholar 

  9. Lorca GL, Barabote RD, Zlotopolski V, Tran C, Winnen B, Hvorup RN, Stonestrom AJ, Nguyen E et al (2007) Transport capabilities of eleven Gram-positive bacteria: comparative genomic analyses. Biochim Biophys Acta 1768:1342–1366. doi:10.1016/j.bbamem.2007.02.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Yen MR, Chen JS, Marquez JL, Sun EI, Saier MH (2010) Multidrug resistance: phylogenetic characterization of superfamilies of secondary carriers that include drug exporters. Methods Mol Biol 637:47–64. doi:10.1007/978-1-60761-700-6_3

    Article  CAS  PubMed  Google Scholar 

  11. Hassan KA, Skurray RA, Brown MH (2007) Transmembrane helix 12 of the Staphylococcus aureus multidrug transporter QacA lines the bivalent cationic drug binding pocket. J Bacteriol 189:9131–9134. doi:10.1128/JB.01492-07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Furukawa H, Tsay JT, Jackowski S, Takamura Y, Rock CO (1993) Thiolactomycin resistance in Escherichia coli is associated with the multidrug resistance efflux pump encoded by emrAB. J Bacteriol 175:3723–3729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Elkins CA, Mullis LB (2006) Mammalian steroid hormones are substrates for the major RND- and MFS-type tripartite multidrug efflux pumps of Escherichia coli. J Bacteriol 188:1191–1195. doi:10.1128/JB.188.3.1191-1195.2006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Naroditskaya V, Schlosser MJ, Fang NY, Lewis K (1993) An E. coli gene emrD is involved in adaptation to low energy shock. Biochem Biophys Res Commun 196:803–809. doi:10.1006/bbrc.1993.2320

    Article  CAS  PubMed  Google Scholar 

  15. Saier MH Jr, Tran CV, Barabote RD (2006) TCDB: the transporter classification database for membrane transport protein analyses and information. Nucleic Acids Res 34:D181–D186. doi:10.1093/nar/gkj001

    Article  CAS  PubMed  Google Scholar 

  16. Edgar R, Bibi E (1997) MdfA, an Escherichia coli multidrug resistance protein with an extraordinarily broad spectrum of drug recognition. J Bacteriol 179:2274–2280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Heng J, Zhao Y, Liu M, Liu Y, Fan J, Wang X, Zhao Y, Zhang XC (2015) Substrate-bound structure of the E. coli multidrug resistance transporter MdfA. Cell Res 25:1060–1073. doi:10.1038/cr.2015.94

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. van Veen HW, Putman M, Margolles A, Sakamoto K, Konings WN (1999) Structure-function analysis of multidrug transporters in Lactococcus lactis. Biochim Biophys Acta 1461:201–206. doi:10.1016/S0005-2736(99)00172-8

    Article  PubMed  Google Scholar 

  19. Saier MH Jr (2003) Tracing pathways of transport protein evolution. Mol Microbiol 48:1145–1156. doi:10.1046/j.1365-2958.2003.03499.x

    Article  CAS  PubMed  Google Scholar 

  20. Maiden MC, Davis EO, Baldwin SA, Moore DC, Henderson PJ (1987) Mammalian and bacterial sugar transport proteins are homologous. Nature 325:641–643. doi:10.1038/325641a0

    Article  CAS  PubMed  Google Scholar 

  21. Hvorup RN, Saier MH Jr (2002) Sequence similarity between the channel-forming domains of voltage-gated ion channel proteins and the C-terminal domains of secondary carriers of the major facilitator superfamily. Microbiology 148:3760–3762. doi:10.1099/00221287-148-12-3760

    Article  CAS  PubMed  Google Scholar 

  22. Paulsen IT, Brown MH, Littlejohn TG, Mitchell BA, Skurray RA (1996) Multidrug resistance proteins QacA and QacB from Staphylococcus aureus: membrane topology and identification of residues involved in substrate specificity. Proc Natl Acad Sci U S A 93:3630–3635

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Huang Y, Lemieux MJ, Song J, Auer M, Wang DN (2003) Structure and mechanism of the glycerol-3-phosphate transporter from Escherichia coli. Science 301:616–620. doi:10.1126/science.1087619

    Article  CAS  PubMed  Google Scholar 

  24. Law CJ, Maloney PC, Wang DN (2008) Ins and outs of major facilitator superfamily antiporters. Annu Rev Microbiol 62:289–305. doi:10.1146/annurev.micro.61.080706.093329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Forrest LR, Kramer R, Ziegler C (2011) The structural basis of secondary active transport mechanisms. Biochim Biophys Acta 1807:167–188. doi:10.1016/j.bbabio.2010.10.014

    Article  CAS  PubMed  Google Scholar 

  26. Bolhuis H, Poelarends G, van Veen HW, Poolman B, Driessen AJ, Konings WN (1995) The lactococcal lmrP gene encodes a proton motive force-dependent drug transporter. J Biol Chem 270:26092–26098. doi:10.1074/jbc.270.44.26092

    Article  CAS  PubMed  Google Scholar 

  27. Bolhuis H, van Veen HW, Brands JR, Putman M, Poolman B, Driessen AJ, Konings WN (1996) Energetics and mechanism of drug transport mediated by the lactococcal multidrug transporter LmrP. J Biol Chem 271:24123–24128

    Article  CAS  PubMed  Google Scholar 

  28. Schaedler TA, van Veen HW (2010) A flexible cation binding site in the multidrug major facilitator superfamily transporter LmrP is associated with variable proton coupling. FASEB J 24:3653–3661. doi:10.1096/fj.10-156927

    Article  CAS  PubMed  Google Scholar 

  29. Bapna A, Federici L, Venter H, Velamakanni S, Luisi B, Fan TP, van Veen HW (2007) Two proton translocation pathways in a secondary active multidrug transporter. J Mol Microbiol Biotechnol 12:197–209. doi:10.1159/000099641

    Article  CAS  PubMed  Google Scholar 

  30. Bibi E, Adler J, Lewinson O, Edgar R (2001) MdfA, an interesting model protein for studying multidrug transport. J Mol Microbiol Biotechnol 3:171–177

    CAS  PubMed  Google Scholar 

  31. Mine T, Morita Y, Kataoka A, Mizushima T, Tsuchiya T (1998) Evidence for chloramphenicol/H+ antiport in Cmr (MdfA) system of Escherichia coli and properties of the antiporter. J Biochem (Tokyo) 124:187–193

    Article  CAS  Google Scholar 

  32. Lewinson O, Adler J, Poelarends GJ, Mazurkiewicz P, Driessen AJ, Bibi E (2003) The Escherichia coli multidrug transporter MdfA catalyzes both electrogenic and electroneutral transport reactions. Proc Natl Acad Sci U S A 100:1667–1672. doi:10.1073/pnas.0435544100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Jin Q, Yuan Z, Xu J, Wang Y, Shen Y, Lu W, Wang J, Liu H et al (2002) Genome sequence of Shigella flexneri 2a: insights into pathogenicity through comparison with genomes of Escherichia coli K12 and O157. Nucleic Acids Res 30:4432–4441. doi:10.1093/nar/gkf566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Parkhill J, Dougan G, James KD, Thomson NR, Pickard D, Wain J, Churcher C, Mungall KL et al (2001) Complete genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18. Nature 413:848–852. doi:10.1038/35101607

    Article  CAS  PubMed  Google Scholar 

  35. Parkhill J, Wren BW, Thomson NR, Titball RW, Holden MT, Prentice MB, Sebaihia M, James KD et al (2001) Genome sequence of Yersinia pestis, the causative agent of plague. Nature 413:523–527. doi:10.1038/35097083

    Article  CAS  PubMed  Google Scholar 

  36. Tirosh O, Sigal N, Gelman A, Sahar N, Fluman N, Siemion S, Bibi E (2012) Manipulating the drug/proton antiport stoichiometry of the secondary multidrug transporter MdfA. Proc Natl Acad Sci U S A 109:12473–12478. doi:10.1073/pnas.1203632109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Adler J, Bibi E (2002) Membrane topology of the multidrug transporter MdfA: complementary gene fusion studies reveal a nonessential C-terminal domain. J Bacteriol 184:3313–3320. doi:10.1128/JB.184.12.3313-3320.2002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Adler J, Lewinson O, Bibi E (2004) Role of a conserved membrane-embedded acidic residue in the multidrug transporter MdfA. Biochemistry 43:518–525. doi:10.1021/bi035485t

    Article  CAS  PubMed  Google Scholar 

  39. Brown MH, Paulsen IT, Skurray RA (1999) The multidrug efflux protein NorM is a prototype of a new family of transporters. Mol Microbiol 31:394–395. doi:10.1046/j.1365-2958.1999.01162.x

    Article  CAS  PubMed  Google Scholar 

  40. Hvorup RN, Winnen B, Chang AB, Jiang Y, Zhou XF, Saier MH Jr (2003) The multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) exporter superfamily. Eur J Biochem 270:799–813. doi:10.1046/j.1432-1033.2003.03418.x

    Article  CAS  PubMed  Google Scholar 

  41. Omote H, Hiasa M, Matsumoto T, Otsuka M, Moriyama Y (2006) The MATE proteins as fundamental transporters of metabolic and xenobiotic organic cations. Trends Pharmacol Sci 27:587–593. doi:10.1016/j.tips.2006.09.001

    Article  CAS  PubMed  Google Scholar 

  42. Moriyama Y, Hiasa M, Matsumoto T, Omote H (2008) Multidrug and toxic compound extrusion (MATE)-type proteins as anchor transporters for the excretion of metabolic waste products and xenobiotics. Xenobiotica 38:1107–1118. doi:10.1080/00498250701883753

    Article  CAS  PubMed  Google Scholar 

  43. Debeaujon I, Peeters AJ, Leon-Kloosterziel KM, Koornneef M (2001) The TRANSPARENT TESTA12 gene of Arabidopsis encodes a multidrug secondary transporter-like protein required for flavonoid sequestration in vacuoles of the seed coat endothelium. Plant Cell 13:853–871, doi:http://dx.doi.org/10.1105/tpc.13.4.853

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Mathews H, Clendennen SK, Caldwell CG, Liu XL, Connors K, Matheis N, Schuster DK, Menasco DJ et al (2003) Activation tagging in tomato identifies a transcriptional regulator of anthocyanin biosynthesis, modification, and transport. Plant Cell 15:1689–1703. doi:10.1105/tpc.012963

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Nawrath C, Heck S, Parinthawong N, Metraux JP (2002) EDS5, an essential component of salicylic acid-dependent signaling for disease resistance in Arabidopsis, is a member of the MATE transporter family. Plant Cell 14:275–286. doi:10.1105/tpc.010376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Yin J, Ye J, Jia W (2012) Effects and mechanisms of berberine in diabetes treatment. Acta Pharm Sin B 2:327–334. doi:10.1016/j.apsb.2012.06.003

    Article  CAS  Google Scholar 

  47. Otani M, Shitan N, Sakai K, Martinoia E, Sato F, Yazaki K (2005) Characterization of vacuolar transport of the endogenous alkaloid berberine in Coptis japonica. Plant Physiol 138:1939–1946. doi:10.1104/pp.105.064352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Facchini PJ (2001) Alkaloid biosynthesis in plants: biochemistry, cell biology, molecular regulation, and metabolic engineering applications. Annu Rev Plant Physiol Plant Mol Biol 52:29–66. PMID: 11337391

    Google Scholar 

  49. Li L, He Z, Pandey GK, Tsuchiya T, Luan S (2002) Functional cloning and characterization of a plant efflux carrier for multidrug and heavy metal detoxification. J Biol Chem 277:5360–5368. doi:10.1074/jbc.M108777200

    Article  CAS  PubMed  Google Scholar 

  50. Durrett TP, Gassmann W, Rogers EE (2007) The FRD3-mediated efflux of citrate into the root vasculature is necessary for efficient iron translocation. Plant Physiol 144:197–205. doi:10.1104/pp.107.097162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Magalhaes JV, Liu J, Guimaraes CT, Lana UG, Alves VM, Wang YH, Schaffert RE, Hoekenga OA et al (2007) A gene in the multidrug and toxic compound extrusion (MATE) family confers aluminum tolerance in sorghum. Nat Genet 39:1156–1161. doi:10.1038/ng2074

    Article  CAS  PubMed  Google Scholar 

  52. Rogers EE, Guerinot ML (2002) FRD3, a member of the multidrug and toxin efflux family, controls iron deficiency responses in Arabidopsis. Plant Cell 14:1787–1799. doi:10.1105/tpc.001495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Morita M, Shitan N, Sawada K, Van Montagu MC, Inze D, Rischer H, Goossens A, Oksman-Caldentey KM et al (2009) Vacuolar transport of nicotine is mediated by a multidrug and toxic compound extrusion (MATE) transporter in Nicotiana tabacum. Proc Natl Acad Sci U S A 106:2447–2452. doi:10.1073/pnas.0812512106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Shoji T, Inai K, Yazaki Y, Sato Y, Takase H, Shitan N, Yazaki K, Goto Y et al (2009) Multidrug and toxic compound extrusion-type transporters implicated in vacuolar sequestration of nicotine in tobacco roots. Plant Physiol 149:708–718. doi:10.1104/pp.108.132811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Burko Y, Geva Y, Refael-Cohen A, Shleizer-Burko S, Shani E, Berger Y, Halon E, Chuck G et al (2011) From organelle to organ: ZRIZI MATE-type transporter is an organelle transporter that enhances organ initiation. Plant Cell Physiol 52:518–527. doi:10.1093/pcp/pcr007

    Article  CAS  PubMed  Google Scholar 

  56. Thompson EP, Wilkins C, Demidchik V, Davies JM, Glover BJ (2010) An Arabidopsis flavonoid transporter is required for anther dehiscence and pollen development. J Exp Bot 61:439–451. doi:10.1093/jxb/erp312

    Article  CAS  PubMed  Google Scholar 

  57. Chen L, Liu Y, Liu H, Kang L, Geng J, Gai Y, Ding Y, Sun H et al (2015) Identification and expression analysis of MATE genes involved in flavonoid transport in blueberry plants. PLoS One 10:e0118578. doi:10.1371/journal.pone.0118578

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Shiomi N, Fukuda H, Fukuda Y, Murata K, Kimura A (1991) Nucleotide sequence and characterization of a gene conferring resistance to ethionine in yeast Saccharomyces cerevisiae. J Ferment Bioeng 71:211–215. doi:10.1016/0922-338X(91)90269-M

    Article  CAS  Google Scholar 

  59. Otsuka M, Matsumoto T, Morimoto R, Arioka S, Omote H, Moriyama Y (2005) A human transporter protein that mediates the final excretion step for toxic organic cations. Proc Natl Acad Sci U S A 102:17923–17928. doi:10.1073/pnas.0506483102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Becker ML, Visser LE, van Schaik RH, Hofman A, Uitterlinden AG, Stricker BH (2009) Genetic variation in the multidrug and toxin extrusion 1 transporter protein influences the glucose-lowering effect of metformin in patients with diabetes: a preliminary study. Diabetes 58:745–749. doi:10.2337/db08-1028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Tsuda M, Terada T, Mizuno T, Katsura T, Shimakura J, Inui K (2009) Targeted disruption of the multidrug and toxin extrusion 1 (Mate1) gene in mice reduces renal secretion of metformin. Mol Pharmacol 75:1280–1286. doi:10.1124/mol.109.056242

    Article  CAS  PubMed  Google Scholar 

  62. Motohashi H, Inui K (2013) Multidrug and toxin extrusion family SLC47: physiological, pharmacokinetic and toxicokinetic importance of MATE1 and MATE2-K. Mol Asp Med 34:661–668. doi:10.1016/j.mam.2012.11.004

    Article  CAS  Google Scholar 

  63. McAleese F, Petersen P, Ruzin A, Dunman PM, Murphy E, Projan SJ, Bradford PA (2005) A novel MATE family efflux pump contributes to the reduced susceptibility of laboratory-derived Staphylococcus aureus mutants to tigecycline. Antimicrob Agents Chemother 49:1865–1871. doi:10.1128/AAC.49.5.1865-1871.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Kaatz GW, McAleese F, Seo SM (2005) Multidrug resistance in Staphylococcus aureus due to overexpression of a novel multidrug and toxin extrusion (MATE) transport protein. Antimicrob Agents Chemother 49:1857–1864. doi:10.1128/AAC.49.5.1857-1864.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Tanihara Y, Masuda S, Sato T, Katsura T, Ogawa O, Inui K (2007) Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H+-organic cation antiporters. Biochem Pharmacol 74:359–371. doi:10.1016/j.bcp.2007.04.010

    Article  CAS  PubMed  Google Scholar 

  66. Guelfo JR, Rodriguez-Rojas A, Matic I, Blazquez J (2010) A MATE-family efflux pump rescues the Escherichia coli 8-oxoguanine-repair-deficient mutator phenotype and protects against H2O2 killing. PLoS Genet 6:e1000931. doi:10.1371/journal.pgen.1000931

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Rodriguez-Beltran J, Rodriguez-Rojas A, Guelfo JR, Couce A, Blazquez J (2012) The Escherichia coli SOS gene dinF protects against oxidative stress and bile salts. PLoS One 7:e34791. doi:10.1371/journal.pone.0034791

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Miller MB, Bassler BL (2001) Quorum sensing in bacteria. Annu Rev Microbiol 55:165–199. doi:10.1146/annurev.micro.55.1.165

    Article  CAS  PubMed  Google Scholar 

  69. Sifri CD (2008) Healthcare epidemiology: quorum sensing: bacteria talk sense. Clin Infect Dis 47:1070–1076. doi:10.1086/592072

    Article  CAS  PubMed  Google Scholar 

  70. Yang S, Lopez CR, Zechiedrich EL (2006) Quorum sensing and multidrug transporters in Escherichia coli. Proc Natl Acad Sci U S A 103:2386–2391. doi:10.1073/pnas.0502890102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. He X, Szewczyk P, Karyakin A, Evin M, Hong WX, Zhang Q, Chang G (2010) Structure of a cation-bound multidrug and toxic compound extrusion transporter. Nature 467:991–994. doi:10.1038/nature09408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Lu M, Symersky J, Radchenko M, Koide A, Guo Y, Nie R, Koide S (2013) Structures of a Na+-coupled, substrate-bound MATE multidrug transporter. Proc Natl Acad Sci U S A 110:2099–2104. doi:10.1073/pnas.1219901110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Tanaka Y, Hipolito CJ, Maturana AD, Ito K, Kuroda T, Higuchi T, Katoh T, Kato HE et al (2013) Structural basis for the drug extrusion mechanism by a MATE multidrug transporter. Nature 496:247–251. doi:10.1038/nature12014

    Article  CAS  PubMed  Google Scholar 

  74. Lu M, Radchenko M, Symersky J, Nie R, Guo Y (2013) Structural insights into H+-coupled multidrug extrusion by a MATE transporter. Nat Struct Mol Biol 20:1310–1317. doi:10.1038/nsmb.2687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Vanni S, Campomanes P, Marcia M, Rothlisberger U (2012) Ion binding and internal hydration in the multidrug resistance secondary active transporter NorM investigated by molecular dynamics simulations. Biochemistry 51:1281–1287. doi:10.1021/bi2015184

    Article  CAS  PubMed  Google Scholar 

  76. Song J, Ji C, Zhang JZ (2014) Insights on Na+ binding and conformational dynamics in multidrug and toxic compound extrusion transporter NorM. Proteins 82:240–249. doi:10.1002/prot.24368

    Article  CAS  PubMed  Google Scholar 

  77. Zhang X, Wright SH (2009) MATE1 has an external COOH terminus, consistent with a 13-helix topology. Am J Physiol Renal Physiol 297:F263–F271. doi:10.1152/ajprenal.00123.2009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Zhang X, He X, Baker J, Tama F, Chang G, Wright SH (2012) Twelve transmembrane helices form the functional core of mammalian MATE1 (multidrug and toxin extruder 1) protein. J Biol Chem 287:27971–27982. doi:10.1074/jbc.M112.386979

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Radchenko M, Symersky J, Nie R, Lu M (2015) Structural basis for the blockade of MATE multidrug efflux pumps. Nat Commun 6:7995. doi:10.1038/ncomms8995

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Tsuruo T, Iida H, Tsukagoshi S, Sakurai Y (1981) Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil. Cancer Res 41:1967–1972

    CAS  PubMed  Google Scholar 

  81. van Veen HW, Venema K, Bolhuis H, Oussenko I, Kok J, Poolman B, Driessen AJ, Konings WN (1996) Multidrug resistance mediated by a bacterial homolog of the human multidrug transporter MDR1. Proc Natl Acad Sci U S A 93:10668–10672

    Article  PubMed  PubMed Central  Google Scholar 

  82. Srikrishna G, Gupta S, Dooley KE, Bishai WR (2015) Can the addition of verapamil to bedaquiline-containing regimens improve tuberculosis treatment outcomes? A novel approach to optimizing TB treatment. Future Microbiol 10:1257–1260. doi:10.2217/FMB.15.56

    Article  CAS  PubMed  Google Scholar 

  83. Otsuka M, Yasuda M, Morita Y, Otsuka C, Tsuchiya T, Omote H, Moriyama Y (2005) Identification of essential amino acid residues of the NorM Na+/multidrug antiporter in Vibrio parahaemolyticus. J Bacteriol 187:1552–1558. doi:10.1128/JB.187.5.1552-1558.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Jin Y, Nair A, van Veen HW (2014) Multidrug transport protein NorM from Vibrio cholerae simultaneously couples to sodium- and proton-motive force. J Biol Chem 289:14624–14632. doi:10.1074/jbc.M113.546770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported by the Biotechnology and Biological Sciences Research Council (UK).

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Authors and Affiliations

  1. Department of Pharmacology, University of Cambridge, Cambridge, UK

    Asha V. Nair, Kenneth W. Lee & Hendrik W. van Veen

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  1. Asha V. Nair
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  2. Kenneth W. Lee
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  3. Hendrik W. van Veen
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Correspondence to Hendrik W. van Veen .

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Editors and Affiliations

  1. Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada

    Xian-Zhi Li

  2. U.S. Food and Drug Administration, Laurel, Maryland, USA

    Christopher A. Elkins

  3. University of Oklahoma, Norman, Oklahoma, USA

    Helen I. Zgurskaya

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Nair, A.V., Lee, K.W., van Veen, H.W. (2016). Structural and Functional Landscape of MFS and MATE Efflux Pumps. In: Li, XZ., Elkins, C., Zgurskaya, H. (eds) Efflux-Mediated Antimicrobial Resistance in Bacteria. Adis, Cham. https://doi.org/10.1007/978-3-319-39658-3_2

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