Assembly and transport mechanism of tripartite drug efflux systems

Biochimica et Biophysica Acta - Proteins and Proteomics

Volumn 1794, Issue 5, 2009, Pages 817-825

  Misra, Rajeev ^a   Bavro, Vassiliy N ^b  

^a ARIZONA STATE UNIVERSITY   (United States)

^b UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

Drug resistance; Membrane fusion protein; Outer membrane protein factor; Proton drug antiporter; RND type multidrug efflux pump; Tripartite pump assembly

Indexed keywords

GLYCOPROTEIN P; PROTEIN ACRA; PROTEIN ACRB; PROTEIN MACA; PROTEIN MEXA; PROTEIN RND; PROTEIN YAJC; TOLC PROTEIN; UNCLASSIFIED DRUG;

ALPHA HELIX; AMINO TERMINAL SEQUENCE; ANTIBIOTIC RESISTANCE; BETA SHEET; CARBOXY TERMINAL SEQUENCE; CRYSTAL STRUCTURE; GENE EXPRESSION REGULATION; GENE MUTATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN ASSEMBLY; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FAMILY; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; PROTEIN TRANSPORT; REVIEW; RNA STRUCTURE; VIBRIO CHOLERAE;

ANTIGENS, BACTERIAL; BACTERIAL OUTER MEMBRANE PROTEINS; BACTERIAL PROTEINS; BIOLOGICAL TRANSPORT; DRUG RESISTANCE, MULTIPLE, BACTERIAL; ESCHERICHIA COLI PROTEINS; LIPOPROTEINS; MEMBRANE FUSION PROTEINS; MEMBRANE TRANSPORT PROTEINS; MULTIDRUG RESISTANCE-ASSOCIATED PROTEINS; PHARMACEUTICAL PREPARATIONS; PROTEIN STRUCTURE, TERTIARY;

BACTERIA (MICROORGANISMS);

EID: 64649089196     PISSN: 15709639     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bbapap.2009.02.017     Document Type: Review

References (84)

1. Piddock L.J. Clinically relevant chromosomally encoded multidrug resistance efflux pumps in bacteria. Clin. Microbio. Rev. 19 (2006) 382-402
2. Poole K. Bacterial multidrug efflux pumps serve other functions. Microbe 3 (2008) 179-185
3. Evans K., Passador L., Srikumar R., Tsang E., Nezezon J., and Poole K. Influence of the MexAB-OprM Multidrug efflux system on quorum sensing in Pseudomonas aeruginosa. J. Bacteriol. 180 (1998) 5443-5447
4. Helling R.B., Janes B.K., Kimball H., Tran T., Bundesmann M., Check P., Phelan D., and Miller C. Toxin disposal in Escherichia coli. J. Bacteriol. 182 (2002) 3699-3703
5. Zakharov S.D., Eroukova V.Y., Rokitskaya T.I., Zhalnina M.V., Sharma O., Loll P.J., Zgurskaya H.I., Antonenko Y.N., and Cramer W.A. Colicin occlusion of OmpF and TolC channels: outer membrane translocons for colicin import. Biophys. J. 87 (2004) 3901-3911
6. Masi M., Vuong P., Humbard M., Malone K., and Misra R. Initial steps of colicin E1 import across the outer membrane of Escherichia coli. J. Bacteriol. 189 (2007) 2667-2676
7. Wandersman C., and Delepelaire P. TolC, an Escherichia coli outer membrane protein required for hemolysin secretion. Proc. Natl. Acad. Sci. U. S. A. 87 (1990) 4776-4780
8. Delepelaire P. Type I secretion in gram-negative bacteria. Biochim. Biophys. Acta 1694 (2004) 149-161
9. Tikhonova E.B., Devroy V.K., Lau S.Y., and Zgurskaya H.I. Reconstitution of the Escherichia coli macrolide transporter: the periplasmic membrane fusion protein MacA stimulates the ATPase activity of MacB. Mol. Microbiol. 63 (2007) 895-910
10. Lin H.T., Bavro V.N., Barrera N.P., Frankish H.M., Velamakanni S., van Veen H.W., Robinson C.V., Borges-Walmsley M.I., and Walmsley A.R. The 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 (2009) 1145-1154
11. Yamanaka H., Kobayashi H., Takahashi E., and Okamoto K. MacAB is involved in the secretion of Escherichia coli heat-stable enterotoxin II. J. Bacteriol. 190 (2008) 7693-7698
12. Lomovskaya O., Zgurskaya H.I., Totrov M., and Watkins W.J. Waltzing transporters and 'the dance macabre' between humans and bacteria. Nat. Rev. 6 (2007) 56-65
13. Murakai S. Multidrug transporters, AcrB-the pumping mechanism. Curr. Opin. Struct. Biol. 18 (2008) 459-465
14. Nikaido H., and Takatsuka Y. Mechanisms of RND multidrug efflux pumps. Biochim. Biophys. Acta 1794 (2009) 763-775
15. Pietras Z., Bavro V.N., Furnham N., Pellegrini-Calace M., Milner-White E.J., and Luisi B.F. Structure and mechanism of drug efflux machinery in Gram negative bacteria. Curr. Drug Targets 9 (2008) 719-728
16. Poole K. Efflux pumps as antimicrobial resistance mechanisms. Ann. Med 39 (2007) 162-176
17. Seeger M.A., Diederichs K., Eicher T., Brandstätter L., Schiefner A., Verrey F., and Pos K.M. The AcrB efflux pump: conformational cycling and peristalsis lead to multidrug resistance. Curr. Drug Targets 9 (2008) 729-749
18. Koronakis V., Sharff A., Koronakis E., Luisi B., and Hughes C. Crystal structure of the bacterial membrane protein TolC central to multidrug efflux and protein export. Nature 405 (2000) 914-919
19. Higgins M.K., Eswaran J., Edwards P., Schertler G.F., Hughes C., and Koronakis V V. Structure of the ligand-blocked periplasmic entrance of the bacterial multidrug efflux protein TolC. J. Mol. Biol. 342 (2004) 697-702
20. Bavro V.N., Pietras Z., Furnham N., Pérez-Cano L., Fernández-Recio J., Pei X.Y., Misra R., and Luisi B. Assembly and channel opening in a bacterial drug efflux machine. Mol. Cell 30 (2008) 114-121
21. Akama H., Kanemaki M., Yoshimura M., Tsukihara T., Kashiwagi T., Yoneyama H., Narita S., Nakagawa A., and Nakae T. 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 (2004) 52816-52819
22. Federici L., Du D., Walas F., Matsumura H., Fernandez-Recio J., McKeegan K.S., Borges-Walmsley M.I., Luisi B.F., and Walmsley A.R. The crystal structure of the outer membrane protein VceC from the bacterial pathogen Vibrio cholerae at 1.8 A resolution. J. Biol. Chem. 280 (2005) 5307-5314
23. Calladine C.R., Sharff A., and Luisi B. How to untwist an alpha-helix: structural principles of an alpha-helical barrel. J. Mol. Biol. 305 (2001) 603-618
24. Andersen C., Koronakis E., Bokma E., Eswaran J., Humphreys D., Hughes C., and Koronakis V. Transition to the open state of the TolC periplasmic tunnel entrance. Proc. Natl. Acad. Sci. U. S. A. 99 (2002) 11103-11108
25. Akama H., Matsuura T., Kashiwagi S., Yoneyama H., Narita S., Tsukihara T., Nakagawa A., and Nakae T. Crystal structure of the membrane fusion protein, MexA, of the multidrug transporter in Pseudomonas aeruginosa. J. Biol. Chem. 279 (2004) 25939-25942
26. Higgins M.K., Bokma E., Koronakis E., Hughes C., and Koronakis V. Structure of the periplasmic component of a bacterial drug efflux pump. Proc. Natl. Acad. Sci. U. S. A. 101 (2004) 9994-9999
27. Mikolosko J.K., Bobyk K., Zgurskaya H.I., and Ghosh P. Conformational flexibility in the multidrug efflux system protein AcrA. Structure 14 (2006) 577-587
28. Elkins C.A., and Nikaido H. Chimeric analysis of AcrA function reveals the importance of its C-terminal domain in its interaction with the AcrB multidrug efflux pump. J. Bacteriol. 185 (2003) 5349-5356
29. Touze T., Eswaran J., Bokma E., Koronakis E., Hughes C., and Koronakis V. Interactions underlying assembly of the Escherichia coli AcrAB-TolC multidrug efflux system. Mol. Microbiol. 53 (2004) 697-706
30. Piao S., Xu Y., and Ha N.C. Crystallization and preliminary X-ray crystallographic analysis of MacA from Actinobacillus actinomycetemcomitans. Acta Crystallogr. Sect. F. Struct. Biol. Cryst. Commun. 64 (2008) 391-393
31. Murakami S., Nakashima R., Yamashita E., and Yamaguchi A. Crystal structure of bacterial multidrug efflux transporter AcrB. Nature 419 (2002) 587-593
32. Murakami S., Nakashima1 R., Yamashita E., Matsumoto T., and Yamaguchi A. Crystal structures of a multidrug transporter reveal a functionally rotating mechanism. Nature 443 (2006) 73-179
33. Seeger M.A., Schiefner A., Eicher T., Verrey F., Diederichs K., and Pos K.M. Structural asymmetry of AcrB trimer suggests a peristaltic pump mechanism. Science 313 (2006) 1295-1298
34. Das D., Xu Q.S., Lee J.Y., Ankoudinova I., Huang C., Lou Y., DeGiovanni A., Kim R., and Kim S.H. Crystal structure of the multidrug efflux transporter AcrB at 3.1 Å resolution reveals the N-terminal region with conserved amino acids. Struct. Biol. 158 (2007) 494-502
35. Sennhauser G., Amstutz P., Briand C., Storchenegger O., and Grütter M.G. Drug export pathway of multidrug exporter AcrB revealed by DARPin inhibitors. PloS Biol. 5 (2007) 106-113
36. Drew D., Klepsch M.M., Newstead S., Flaig R., de Gier J.W., Iwata S., and Beis K. The structure of the efflux pump AcrB in complex with bile acid. Mol. Membr. Biol. 25 (2008) 677-682
37. Zgurskaya H.I., and Nikaodo H. Cross-linked complex between oligomeric periplasmic lipoprotein AcrA and the inner-membrane-associated multidrug efflux pump AcrB from Escherichia coli. J. Bacteriol. 182 (2000) 4264-4267
38. Thanabalu T., Koronakis E., Hughes C., and Koronakis V. 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 (1998) 6487-6496
39. Eswaran J., Koronakis E., Higgins M.K., Hughes C., and Koronakis V. Three's company: component structures bring a closer view of tripartite drug efflux pumps. Curr. Opin. Struct. Biol. 14 (2004) 741-747
40. Fernandez-Recio J., Walas F., Federici L., Venkatesh Pratap J., Bavro V.N., Miguel R.N., Mizuguchi K., and Luisi B. A model of a transmembrane drug-efflux pump from Gram-negative bacteria. FEBS Lett. 578 (2004) 5-9
41. Lobedanz S., Bokma E., Symmons M.F., Koronakis E., Hughes C., and Koronakis V. A periplasmic coiled-coil interface underlying TolC recruitment and the assembly of bacterial drug efflux pumps. Proc. Natl. Acad. Sci. U. S. A. 104 (2007) 4612-4617
42. Bunikis I., Denker K., Ostberg Y., Andersen C., Benz R., and Bergström S. An RND-type efflux system in Borrelia burgdorferi is involved in virulence and resistance to antimicrobial compounds. PLoS Pathog. 4 (2008) 1-11
43. Stegmeier J.F., Polleichtner G., Brandes N., Hotz C., and Andersen C. Importance of the adaptor (membrane fusion) protein hairpin domain for the functionality of multidrug efflux pumps. Biochemistry 45 (2006) 10303-10312
44. Narita S.-I., Eda S., Yoshihara E., and Nakae T. Linkage of the efflux-pump expression level with substrate extrusion rate in the MexAB-OprM efflux pump of Pseudomonas aeruginosa. Biochem. Biophys. Res. Commun. 308 (2003) 922-926
45. Mima T., Joshi S., Gomez-Escalada M., and Schweizer H.P. Identification and characterization of TriABC-OpmH, a triclosan efflux pump of Pseudomonas aeruginosa requiring two membrane fusion proteins. J. Bacteriol. 189 (2007) 76007609
46. Gristwood T., Fineran P.C., Everson L., and Salmond G.P. PigZ, a TetR/AcrR family repressor, modulates secondary metabolism via the expression of a putative four-component resistance-nodulation-cell-division efflux pump, ZrpADBC, in Serratia sp. ATCC 39006. Mol. Microbiol. 69 (2008) 418-435
47. Avila-Sakar A.J., Misaghi S., Wilson-Kubalek E.M., Downing K.H., Zgurskaya H.I., Nikaido H., and Nogales E. 2D crystals of AcrA appear to accommodate a central cavity. J. Struct. Biol. 136 (2001) 81-88
48. Trépout S., Taveau J.C., Mornet S., Benabdelhak H., Ducruix A., and Lambert O. Organization of reconstituted lipoprotein MexA onto supported lipid membrane. Eur. Biophys. J. 36 (2007) 1029-1037
49. Tamura N., Murakami S., Oyama Y., Ishiguro M., and Yamaguchi A. Direct interaction of multidrug efflux transporter AcrB and outer membrane channel TolC detected via site-directed disulfide cross-linking. Biochemistry 44 (2005) 11115-11121
50. Mokhonov V.V., Akama A., and Nakae T. Role of the membrane fusion protein in the assembly of resistance-nodulation-cell division multidrug efflux pump in Pseudomonas aeruginosa. Biochem. Biophys. Res. Commun. 322 (2004) 483-489
51. Nehme D., Li X.Z., Elliot R., and Poole K. 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 (2004) 2973-2983
52. Gerken H., and Misra R. Genetic evidence for functional interactions between TolC and AcrA proteins of a major antibiotic efflux pump of Escherichia coli. Mol. Microbial. 54 (2004) 620-631
53. Nehme D., and Poole K. Interaction of the MexA and MexB components of the MexAB-OprM multidrug efflux system of Pseudomonas aeruginosa: identification of MexA extragenic suppressors of a T578I mutation in MexB. Antibicrob. Agents Chemother. 49 (2005) 4375-4378
54. Nehme D., and Poole K. Assembly of the MexAB-OprM multidrug pump of Pseudomonas aeruginosa: component interactions defined by the study of pump mutant suppressors. J. Bacteriol. 189 (2007) 6118-6127
55. Vediyappan G., Borisova T., and Fralick J.A. Isolation and characterization of VceC gain-of-function mutants that can function with the AcrAB multiple-drug-resistant efflux pump of Escherichia coli. J. Bacteriol. 188 (2006) 3757-3762
56. Krishnamoorthy G., Tikhonova E.B., and Zgurskaya H.I. Fitting periplasmic membrane fusion proteins to inner membrane transporters: mutations that enable Escherichia coli AcrA to function with Pseudomonas aeruginosa MexB. J. Bacteriol. 190 (2008) 691-698
57. Bokma E., Koronakis E., Lobedanz S., Hughes C., and Koronakis V. Directed evolution of a bacterial efflux pump: adaptation of the E. coli TolC exit duct to the Pseudomonas MexAB translocase. FEBS Lett. 580 (2006) 5339-5343
58. Husain F., Humbard M., and Misra R. Interaction between the TolC and AcrA proteins of a multidrug efflux system of Escherichia coli. J. Bacteriol. 186 (2004) 8533-8536
59. Elkins C.A., and Nikaido H. 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 (2002) 6490-6498
60. Tikhonova E.B., Wang Q., and Zgurskaya H.I. Chimeric analysis of the multicomponent multidrug efflux transporters from gram negative bacteria. J. Bacteriol. 184 (2002) 6499-6507
61. Eda S., Maseda H., Yoshihara E., and Nakae T. Assignment of the outer-membrane-subunit-selective domain of the membrane fusion protein in the tripartite xenobiotic efflux pump of Pseudomonas aeruginosa. FEMS Microbiol. Lett. 254 (2006) 101-107
62. Tikhonova E.B., and Zgurskaya H.I. AcrA, AcrB, and TolC of Escherichia coli form a stable intermembrane multidrug efflux complex. J. Biol. Chem. 279 (2004) 32116-32124
63. Andersen C., Koronakis E., Hughes C., and Koronakis V. An aspartate ring at the TolC tunnel entrance determines ion selectivity and presents a target for blocking by large cations. Mol. Microbiol. 44 (2002) 1131-1139
64. Eswaran J., Hughes C., and Koronakis V. Locking TolC entrance helices to prevent protein translocation by the bacterial type I export apparatus. J. Mol. Biol. 327 (2003) 309-315
65. Augustus A.M., Celaya T., Husain F., Humbard M., and Misra R. Antibiotic-sensitive TolC mutants and their suppressors. J. Bacteriol. 186 (2004) 1851-1860
66. Gough J., Karplus K., Hughey R., and Chothia C. Assignment of homology to genome sequences using a library of hidden Markov models that represent all proteins of known structure. J. Mol. Biol. 313 (2001) 903-919
67. Eda S., Yoneyama H., and Nakae T. Function of the MexB efflux-transporter divided into two halves. Biochemistry 42 (2003) 7238-7244
68. Murakami S., and Yamaguchi A. Multidrug-exporting secondary transporters. Curr. Opin. Struct. Biol. 13 (2003) 443-452
69. Yu E.W., McDermott G., Zgurskaya H.I., Nikaido H., and Koshland Jr. D.E. Structural basis of multiple drug-binding capacity of the AcrB multidrug efflux pump. Science 300 (2003) 976-980
70. Yu E.W., Aires J.R., McDermott G., and Nikaido H. A periplasmic drug-binding site of the AcrB multidrug efflux pump: a crystallographic and site-directed mutagenesis study. J. Bacteriol. 187 (2005) 6804-6815
71. Seeger M.A., von Ballmoos C., Eicher T., Brandstätter L., Verrey F., Diederichs K., and Pos K.M. Engineered disulfide bonds support the functional rotation mechanism of multidrug efflux pump AcrB. Nature Struct. Mol. Biol. 15 (2008) 199-205
72. Dastidar V., Mao W., Lomovskaya O., and Zgurskaya H.I. Drug-induced conformational changes in multidrug efflux transporter AcrB from Haemophilus influenzae. J. Bacteriol. 189 (2007) 5550-5558
73. Takatsuka Y., and Nikaido H. Site-directed disulfide cross-linking shows that cleft flexibility in the periplasmic domain is needed for the multidrug efflux pump AcrB of Escherichia coli. J. Bacteriol. 189 (2007) 8677-8684
74. Murakami S., Tamura N., Saito A., Hirata T., and Yamaguchi A. Extramembrane central pore of multidrug exporter AcrB in Escherichia coli plays an important role in drug transport. J. Biol. Chem. 279 (2004) 3743-3748
75. Takasuka Y., and Nikaido H. Covalently linked trimer of the AcrB multidrug efflux pump provides support for the functional rotating mechanism. J. Bacteriol. 191 (2009) 1729-1737
76. Törnroth-Horsefield S., Gourdon P., Horsefield R., Brive L., Yamamoto N., Mori H., Snijder A., and Neutze1 R. Crystal structure of AcrB in complex with a single transmembrane subunit reveals another twist. Structure 15 (2007) 1663-1673
77. Su C.C., Li M., Gu R., Takatsuka Y., McDermott G., Nikaido H., and Yu E.W. Conformation of the AcrB multidrug efflux pump in mutants of the putative proton relay pathway. J. Bacteriol. 188 (2006) 7290-7296
78. Guan L., and Nakae T. Identification of essential charged residues in transmembrane segments of the multidrug transporter MexB of Pseudomonas aeruginosa. J. Bacteriol. 183 (2001) 1734-1739
79. Takatsuka Y., and Nikaido H. Threonine-978 in the transmembrane segment of the multidrug efflux pump AcrB of Escherichia coli is crucial for drug transport as a probable component of the proton relay network. J. Bacteriol. 188 (2006) 7284-7289
80. Doung F., and Wickner W. Distinct catalytic roles of the SecYE, SecG and SecDFyajC subunits of preprotein translocase holoenzyme. EMBO J. 16 (1997) 2756-2768
81. Taura T., Akiyama Y., and Ito K. Genetic analysis of SecY: additional export-defective mutations and factors affecting their phenotypes. Mol. Gen. Genet. 243 (1994) 261-269
82. Mahamoud A., Chevalier J., Alibert-Franco S., Kern W.V., and Pagès J.-M. Antibiotic efflux pumps in Gram-negative bacteria: the inhibitor response strategy. J. Antimicrob. Chemother. 59 (2007) 1223-1229
83. Pagès J.-M., and Amaral L. Mechanisms of drug efflux and strategies to combat them: challenging the efflux pump of Gram negative bacteria. Biochim. Biophys. Acta 1794 (2009) 826-833
84. Alibert-Franco S., Pradines B., Mahamoud A., Davin-Regli A., and Pagès J.-M. Efflux mechanism, an attractive target to combat multidrug resistant plasmodium falciparum and Pseudomonas aeruginosa. Curr. Med. Chem. 16 (2009) 301-317