Advanced search
Publication Cover
Future Microbiology Volume 4, 2009 - Issue 7
Submit an article Journal homepage
162
Views
0
CrossRef citations to date
0
Altmetric
Review

Multicomponent Drug Efflux Complexes: Architecture and Mechanism of Assembly

Helen I ZgurskayaDepartment of Chemistry & Biochemistry, University of Oklahoma, 620 Parrington Oval, Room 208, Norman, OK73019, USA.Tel.: +14053251678 Fax: [email protected]View further author information
Pages 919-932 | Published online: 01 Sep 2009

Bibliography

  • Levy SB , MarshallB: Antibacterial resistance worldwide: causes, challenges and responses.Nat. Med.10 , S122–S129 (2004).
  • Livermore DM : The need for new antibiotics.Clin. Microbiol. Infect.10(Suppl. 4) , 1–9 (2004).
  • Nikaido H , VaaraM: Molecular basis of bacterial outer membrane permeability.Microbiol. Rev.49 , 1–32 (1985).
  • Lomovskaya O , LewisK: Emr, an Escherichia coli locus for multidrug resistance.Proc. Natl Acad. Sci. USA89 , 8938–8942 (1992).
  • Ma D , CookDN, AlbertiMet al.: Molecular cloning and characterization of acrA and acrE genes of Escherichia coli.J. Bacteriol.175 , 6299–6313 (1993).
  • Lomovskaya O , ZgurskayaHI, TotrovM, WatkinsWJ: Waltzing transporters and ‘the dance macabre‘ between humans and bacteria.Nat. Rev. Drug Discov.6 , 56–65 (2007).
  • Nikaido H : Preventing drug access to targets: cell surface permeability barriers and active efflux in bacteria.Semin. Cell Dev. Biol.12 , 215–223 (2001).
  • Zgurskaya HI , KrishnamoorthyG, TikhonovaEB, LauSY, StrattonKL: Mechanism of antibiotic efflux in Gram-negative bacteria.Front. Biosci.8 , s862–s873 (2003).
  • Dinh T , PaulsenIT, SaierMH Jr: A family of extracytoplasmic proteins that allow transport of large molecules across the outer membranes of Gram-negative bacteria. J. Bacteriol.176 , 3825–3831 (1994).
  • Aires JR , NikaidoH: Aminoglycosides are captured from both periplasm and cytoplasm by the AcrD multidrug efflux transporter of Escherichia coli.J. Bacteriol.187 , 1923–1929 (2005).
  • Tikhonova EB , DevroyVK, LauSY, ZgurskayaHI: Reconstitution of the Escherichia coli macrolide transporter: the periplasmic membrane fusion protein MacA stimulates the ATPase activity of MacB.Mol. Microbiol.63 , 895–910 (2007).
  • Zgurskaya HI , NikaidoH: Bypassing the periplasm: reconstitution of the AcrAB multidrug efflux pump of Escherichia coli.Proc. Natl Acad. Sci. USA96 , 7190–7195 (1999).
  • Andersen C , HughesC, KoronakisV: Protein export and drug efflux through bacterial channel-tunnels.Curr. Opin. Cell Biol.13 , 412–416 (2001).
  • Thanabalu T , KoronakisE, HughesC, KoronakisV: Substrate-induced assembly of a contiguous channel for protein export from E. coli: reversible bridging of an inner-membrane translocase to an outer membrane exit pore.EMBO J.17 , 6487–6496 (1998).
  • Paulsen IT , ChenJ, NelsonKE, SaierMH Jr: Comparative genomics of microbial drug efflux systems. J. Mol. Microbiol. Biotechnol.3 , 145–150 (2001).
  • Saier MH Jr, Beatty JT, Goffeau A et al.: The major facilitator superfamily. J. Mol. Microbiol. Biotechnol.1 , 257–279 (1999).
  • Tseng TT , GratwickKS, KollmanJet al.: The RND permease superfamily: an ancient, ubiquitous and diverse family that includes human disease and development proteins.J. Mol. Microbiol. Biotechnol.1 , 107–125 (1999).
  • Saier MH Jr, Paulsen IT, Sliwinski MK et al.: Evolutionary origins of multidrug and drug-specific efflux pumps in bacteria. FASEB J.12 , 265–274 (1998).
  • Poole K : Efflux-mediated multiresistance in Gram-negative bacteria.Clin. Microbiol. Infect.10 , 12–26 (2004).
  • Sobel ML , HocquetD, CaoL, PlesiatP, PooleK: Mutations in PA3574 (nalD) lead to increased MexAB–OprM expression and multidrug resistance in laboratory and clinical isolates of Pseudomonas aeruginosa.Antimicrob. Agents Chemother.49 , 1782–1786 (2005).
  • Zgurskaya HI , NikaidoH: Multidrug resistance mechanisms: drug efflux across two membranes.Mol. Microbiol.37 , 219–225 (2000).
  • Nikaido H , ZgurskayaHI: AcrAB and related multidrug efflux pumps of Escherichia coli.J. Mol. Microbiol. Biotechnol.3 , 215–218 (2001).
  • Koronakis V , SharffA, KoronakisE, LuisiB, HughesC: Crystal structure of the bacterial membrane protein TolC central to multidrug efflux and protein export.Nature405 , 914–919 (2000).
  • Mikolosko J , BobykK, ZgurskayaHI, GhoshP: Conformational flexibility in the multidrug efflux system protein AcrA.Structure14 , 577–587 (2006).
  • Murakami S , NakashimaR, YamashitaE, YamaguchiA: Crystal structure of bacterial multidrug efflux transporter AcrB.Nature419 , 587–593 (2002).
  • Akama H , KanemakiM, YoshimuraMet al.: 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 , 52816–52819 (2004).
  • Akama H , MatsuuraT, KashiwagiSet al.: Crystal structure of the membrane fusion protein, MexA, of the multidrug transporter in Pseudomonas aeruginosa.J. Biol. Chem.279 , 25939–25942 (2004).
  • Sennhauser G , BukowskaMA, BriandC, GrutterMG: Crystal structure of the multidrug exporter MexB from Pseudomonas aeruginosa.J. Mol. Biol.389 , 134–145 (2009).
  • Murakami S , NakashimaR, YamashitaE, MatsumotoT, YamaguchiA: Crystal structures of a multidrug transporter reveal a functionally rotating mechanism.Nature443 , 173–179 (2006).
  • Yu EW , AiresJR, McDermottG, NikaidoH: A periplasmic drug-binding site of the AcrB multidrug efflux pump: a crystallographic and site-directed mutagenesis study.J. Bacteriol.187 , 6804–6815 (2005).
  • Yu EW , McDermottG, ZgurskayaHI, NikaidoH, KoshlandDE Jr: Structural basis of multiple drug-binding capacity of the AcrB multidrug efflux pump. Science300 , 976–980 (2003).
  • Seeger MA , SchiefnerA, EicherTet al.: Structural asymmetry of AcrB trimer suggests a peristaltic pump mechanism.Science313 , 1295–1298 (2006).
  • Murakami S : Multidrug efflux transporter, AcrB – the pumping mechanism.Curr. Opin. Struct. Biol.18 , 459–465 (2008).
  • Nikaido H , TakatsukaY: Mechanisms of RND multidrug efflux pumps.Biochim. Biophys. Acta1794 , 769–781 (2009).
  • Pos KM : Drug transport mechanism of the AcrB efflux pump.Biochim. Biophys. Acta1794 , 782–793 (2009).
  • Seeger MA , von Ballmoos C, Eicher T et al.: Engineered disulfide bonds support the functional rotation mechanism of multidrug efflux pump AcrB. Nat. Struct. Mol. Biol.15 , 199–205 (2008).
  • Takatsuka Y , NikaidoH: Site-directed disulfide crosslinking shows that cleft flexibility in the periplasmic domain is needed for the multidrug efflux pump AcrB of Escherichia coli.J. Bacteriol.189 , 8677–8684 (2007).
  • Su CC , LiM, GuRet al.: Conformation of the AcrB multidrug efflux pump in mutants of the putative proton relay pathway.J. Bacteriol.188 , 7290–7296 (2006).
  • Tikhonova EB , ZgurskayaHI: AcrA, AcrB, and TolC of Escherichia coli form a stable intermembrane multidrug efflux complex.J. Biol. Chem.279 , 32116–32124 (2004).
  • Takatsuka Y , NikaidoH: Covalently linked trimer of the AcrB multidrug efflux pump provides support for the functional rotating mechanism.J. Bacteriol.191 , 1729–1737 (2009).
  • Nagano K , NikaidoH: Kinetic behavior of the major multidrug efflux pump AcrB of Escherichia coli.Proc. Natl Acad. Sci. USA106 , 5854–5858 (2009).
  • Federici L , DuD, WalasFet al.: The crystal structure of the outer membrane protein VceC from the bacterial pathogen Vibrio cholerae at 1.8 Å resolution.J. Biol. Chem.280 , 15307–15314 (2005).
  • Andersen C , KoronakisE, BokmaEet al.: Transition to the open state of the TolC periplasmic tunnel entrance.Proc. Natl Acad. Sci. USA99 , 11103–11108 (2002).
  • Bavro VN , PietrasZ, FurnhamNet al.: Assembly and channel opening in a bacterial drug efflux machine.Mol. Cell30 , 114–121 (2008).
  • Touze T , EswaranJ, BokmaEet al.: Interactions underlying assembly of the Escherichia coli AcrAB–TolC multidrug efflux system.Mol. Microbiol.53 , 697–706 (2004).
  • Borges-Walmsley MI , BeauchampJ, KellySMet al.: Identification of oligomerization and drug-binding domains of the membrane fusion protein EmrA.J. Biol. Chem.278 , 12903–12912 (2003).
  • Pimenta AL , RacherK, JamiesonL, BlightMA, HollandIB: Mutations in HlyD, part of the type 1 translocator for hemolysin secretion, affect the folding of the secreted toxin.J. Bacteriol.187 , 7471–7480 (2005).
  • Bagai I , LiuW, RensingC, BlackburnNJ, McEvoyMM: Substrate-linked conformational change in the periplasmic component of a Cu(I)/Ag(I) efflux system.J. Biol. Chem.282 , 35695–35702 (2007).
  • Zgurskaya HI , YamadaY, TikhonovaEB, GeQ, KrishnamoorthyG: Structural and functional diversity of bacterial membrane fusion proteins.Biochim. Biophys. Acta1794 , 794–807 (2009).
  • Symmons MF , BokmaE, KoronakisE, HughesC, KoronakisV: The assembled structure of a complete tripartite bacterial multidrug efflux pump.Proc. Natl Acad. Sci. USA106 , 7173–7178 (2009).
  • Krishnamoorthy G , TikhonovaEB, ZgurskayaHI: Fitting periplasmic membrane fusion proteins to inner membrane transporters: mutations that enable Escherichia coli AcrA to function with Pseudomonas aeruginosa MexB.J. Bacteriol.190 , 691–698 (2008).
  • Lobedanz S , BokmaE, SymmonsMFet al.: A periplasmic coiled–coil interface underlying TolC recruitment and the assembly of bacterial drug efflux pumps.Proc. Natl Acad. Sci. USA104 , 4612–4617 (2007).
  • Ip H , StrattonK, ZgurskayaH, LiuJ: pH-induced conformational changes of AcrA, the membrane fusion protein of Escherichia coli multidrug efflux system.J. Biol. Chem.278 , 50474–50482 (2003).
  • Ge Q , YamadaY, ZgurskayaH: The C-terminal domain of AcrA is essential for the assembly and function of the multidrug efflux pump AcrAB–TolC.J. Bacteriol.191 , 4365–4371 (2009).
  • Misra R , BavroVN: Assembly and transport mechanism of tripartite drug efflux systems.Biochim. Biophys. Acta1794 , 817–825 (2009).
  • Reffay M , GambinY, BenabdelhakHet al.: Tracking membrane protein association in model membranes.PLoS One4 , e5035 (2009).
  • Davis DR , McAlpineJB, PazolesCJet al.: Enterococcus faecalis multi-drug resistance transporters: application for antibiotic discovery.J. Mol. Microbiol. Biotechnol.3 , 179–184 (2001).
  • Paulsen IT , ParkJH, ChoiPS, SaierMH Jr: A family of Gram-negative bacterial outer membrane factors that function in the export of proteins, carbohydrates, drugs and heavy metals from Gram-negative bacteria. FEMS Microbiol. Lett.156 , 1–8 (1997).
  • Davidson AL , DassaE, OrelleC, ChenJ: Structure, function, and evolution of bacterial ATP-binding cassette systems.Microbiol. Mol. Biol. Rev.72 , 317–364 (2008).
  • Seeger MA , van Veen HW: Molecular basis of multidrug transport by ABC transporters. Biochim. Biophys. Acta1794 , 725–737 (2009).
  • Locher KP : Review. Structure and mechanism of ATP-binding cassette transporters.Philos. Trans. R. Soc. Lond. B Biol. Sci.364 , 239–245 (2009).
  • Kobayashi N , NishinoK, HirataT, YamaguchiA: Membrane topology of ABC-type macrolide antibiotic exporter MacB in Escherichia coli.FEBS Lett.546 , 241–246 (2003).
  • Xu Y , SimSH, NamKHet al.: Crystal structure of the periplasmic region of MacB, a noncanonic ABC transporter.Biochemistry48 , 5218–5225 (2009).
  • Aller SG , YuJ, WardAet al.: Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding.Science323 , 1718–1722 (2009).
  • Dawson RJ , LocherKP: Structure of a bacterial multidrug ABC transporter.Nature443 , 180–185 (2006).
  • Reyes CL , ChangG: Structure of the ABC transporter MsbA in complex with ADP.vanadate and lipopolysaccharide.Science308 , 1028–1031 (2005).
  • Rosenberg MF , MaoQ, HolzenburgAet al.: The structure of the multidrug resistance protein 1 (MRP1/ABCC1) crystallization and single-particle analysis.J. Biol. Chem.276 , 16076–16082 (2001).
  • Pleban K , KoppS, CsaszarEet al.: P-glycoprotein substrate binding domains are located at the transmembrane domain/transmembrane domain interfaces: a combined photoaffinity labeling-protein homology modeling approach.Mol. Pharmacol.67 , 365–374 (2005).
  • Reyes CL , WardA, YuJ, ChangG: The structures of MsbA: insight into ABC transporter-mediated multidrug efflux.FEBS Lett.580 , 1042–1048 (2006).
  • Higgins CF , LintonKJ: The ATP switch model for ABC transporters.Nat. Struct. Mol. Biol.11 , 918–926 (2004).
  • Senior AE : Catalytic mechanism of P-glycoprotein.Acta Physiol. Scand. Suppl.643 , 213–218 (1998).
  • Hollenstein K , DawsonRJ, LocherKP: Structure and mechanism of ABC transporter proteins.Curr. Opin. Struct. Biol.17 , 412–418 (2007).
  • Oldham ML , DavidsonAL, ChenJ: Structural insights into ABC transporter mechanism.Curr. Opin. Struct. Biol.18 , 726–733 (2008).
  • Holland IB , BlightMA, KennyB: The mechanism of secretion of hemolysin and other polypeptides from Gram-negative bacteria.J. Bioenerg. Biomembr.22 , 473–491 (1990).
  • Delepelaire P : PrtD, the integral membrane ATP-binding cassette component of the Erwinia chrysanthemi metalloprotease secretion system, exhibits a secretion signal-regulated ATPase activity.J. Biol. Chem.269 , 27952–27957 (1994).
  • Gilson L , MahantyHK, KolterR: Genetic analysis of an MDR-like export system: the secretion of colicin V.EMBO J.9 , 3875–3894 (1990).
  • Kobayashi N , NishinoK, YamaguchiA: Novel macrolide-specific ABC-type efflux transporter in Escherichia coli.J. Bacteriol.183 , 5639–5644 (2001).
  • Yamanaka H , KobayashiH, TakahashiE, OkamotoK: MacAB is involved in the secretion of Escherichia coli heat-stable enterotoxin II.J. Bacteriol.190 , 7693–7698 (2008).
  • Dubern JF , CoppoolseER, StiekemaWJ, BloembergGV: Genetic and functional characterization of the gene cluster directing the biosynthesis of putisolvin I and II in Pseudomonas putida strain PCL1445.Microbiology154 , 2070–2083 (2008).
  • Johnson JM , ChurchGM: Alignment and structure prediction of divergent protein families: periplasmic and outer membrane proteins of bacterial efflux pumps.J. Mol. Biol.287 , 695–715 (1999).
  • Balakrishnan L , HughesC, KoronakisV: Substrate-triggered recruitment of the TolC channel-tunnel during type I export of hemolysin by Escherichia coli.J. Mol. Biol.313 , 501–510 (2001).
  • Yum S , XuY, PiaoSet al.: Crystal structure of the periplasmic component of a tripartite macrolide-specific efflux pump.J. Mol. Biol.387 , 1286–1297 (2009).
  • Lin HT , BavroVN, BarreraNPet al.: MacB ABC transporter is a dimer whose ATPase activity and macrolide-binding capacity are regulated by the membrane fusion protein MacA.J. Biol. Chem.284 , 1145–1154 (2009).
  • Nikaido H , HallJA: Overview of bacterial ABC transporters.Methods Enzymol.292 , 3–20 (1998).
  • Yu EW , AiresJR, NikaidoH: AcrB multidrug efflux pump of Escherichia coli: composite substrate-binding cavity of exceptional flexibility generates its extremely wide substrate specificity.J. Bacteriol.185 , 5657–5664 (2003).
  • Tikhonova EB , WangQ, ZgurskayaHI: Chimeric analysis of the multicomponent multidrug efflux transporters from Gram-negative bacteria.J. Bacteriol.184 , 6499–6507 (2002).
  • Nehme D , LiXZ, ElliotR, PooleK: Assembly of the MexAB–OprM multidrug efflux system of Pseudomonas aeruginosa: identification and characterization of mutations in mexA compromising MexA multimerization and interaction with MexB.J. Bacteriol.186 , 2973–2983 (2004).
  • Mao W , WarrenMS, BlackDSet al.: On the mechanism of substrate specificity by resistance nodulation division (RND)-type multidrug resistance pumps: the large periplasmic loops of MexD from Pseudomonas aeruginosa are involved in substrate recognition.Mol. Microbiol.46 , 889–901 (2002).
  • Elkins CA , NikaidoH: Substrate specificity of the RND-type multidrug efflux pumps AcrB and AcrD of Escherichia coli is determined predominately by two large periplasmic loops.J. Bacteriol.184 , 6490–6498 (2002).
  • Middlemiss JK , PooleK: Differential impact of MexB mutations on substrate selectivity of the MexAB–OprM multidrug efflux pump of Pseudomonas aeruginosa.J. Bacteriol.186 , 1258–1269 (2004).
  • Paulsen IT , BrownMH, SkurrayRA: Characterization of the earliest known Staphylococcus aureus plasmid encoding a multidrug efflux system.J. Bacteriol.180 , 3477–3479 (1998).
  • Brown MH , SkurrayRA: Staphylococcal multidrug efflux protein QacA.J. Mol. Microbiol. Biotechnol.3 , 163–170 (2001).
  • Bolhuis H , PoelarendsG, van Veen HW et al.: The lactococcal lmrP gene encodes a proton motive force-dependent drug transporter. J. Biol. Chem.270 , 26092–26098 (1995).
  • Neyfakh AA : The multidrug efflux transporter of Bacillus subtilis is a structural and functional homolog of the Staphylococcus NorA protein.Antimicrob. Agents Chemother.36 , 484–485 (1992).
  • Lewinson O , AdlerJ, PoelarendsGJet al.: The Escherichia coli multidrug transporter MdfA catalyzes both electrogenic and electroneutral transport reactions.Proc. Natl Acad. Sci. USA100 , 1667–1672 (2003).
  • Abramson J , SmirnovaI, KashoVet al.: Structure and mechanism of the lactose permease of Escherichia coli.Science301 , 610–615 (2003).
  • Yin Y , HeX, SzewczykP, NguyenT, ChangG: Structure of the multidrug transporter EmrD from Escherichia coli.Science312 , 741–744 (2006).
  • Lemieux MJ , HuangY, WangDN: The structural basis of substrate translocation by the Escherichia coli glycerol-3-phosphate transporter: a member of the major facilitator superfamily.Curr. Opin. Struct. Biol.14 , 405–412 (2004).
  • Fluman N , BibiE: Bacterial multidrug transport through the lens of the major facilitator superfamily.Biochim. Biophys. Acta1794 , 738–747 (2009).
  • Saidijam M , BenedettiG, RenQet al.: Microbial drug efflux proteins of the major facilitator superfamily.Curr. Drug Targets7 , 793–811 (2006).
  • Smirnova I , KashoV, ChoeJYet al.: Sugar binding induces an outward facing conformation of LacY.Proc. Natl Acad. Sci. USA104 , 16504–16509 (2007).
  • Zhou Y , GuanL, FreitesJA, KabackHR: Opening and closing of the periplasmic gate in lactose permease.Proc. Natl Acad. Sci. USA105 , 3774–3778 (2008).
  • Sigal N , Molshanski-MorS, BibiE: No single irreplaceable acidic residues in the Escherichia coli secondary multidrug transporter MdfA.J. Bacteriol.188 , 5635–5639 (2006).
  • Bapna A , FedericiL, VenterHet al.: Two proton translocation pathways in a secondary active multidrug transporter.J. Mol. Microbiol. Biotechnol.12 , 197–209 (2007).
  • Schuldiner S : EmrE, a model for studying evolution and mechanism of ion-coupled transporters.Biochim. Biophys. Acta1794 , 748–762 (2009).
  • Elkins CA , MullisLB: Mammalian steroid hormones are substrates for the major RND- and MFS-type tripartite multidrug efflux pumps of Escherichia coli.J. Bacteriol.188 , 1191–1195 (2006).
  • Brown MH , SkurrayRA: Staphylococcal multidrug efflux protein QacA.J. Mol. Microbiol. Biotechnol.3 , 163–170 (2001).
  • Mitchell BA , PaulsenIT, BrownMH, SkurrayRA: Bioenergetics of the staphylococcal multidrug export protein QacA. Identification of distinct binding sites for monovalent and divalent cations.J. Biol. Chem.274 , 3541–3548 (1999).
  • Guan L , KabackHR: Lessons from lactose permease.Annu. Rev. Biophys. Biomol. Struct.35 , 67–91 (2006).
  • Sigal N , LewinsonO, WolfSG, BibiE: E. coli multidrug transporter MdfA is a monomer.Biochemistry46 , 5200–5208 (2007).
  • Tanabe M , SzakonyiG, BrownKAet al.: The multidrug resistance efflux complex, EmrAB from Escherichia coli forms a dimer in vitro.Biochem. Biophys. Res. Commun.380 , 338–342 (2009).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.