acrA

Summary

Gene Symbol: acrA
Description: multidrug efflux system
Alias: ECK0457, JW0452, lir, mbl, mtcA, nbsA, sipB
Species: Escherichia coli str. K-12 substr. MG1655

Top Publications

  1. Tamura N, Murakami S, Oyama Y, Ishiguro M, Yamaguchi A. Direct interaction of multidrug efflux transporter AcrB and outer membrane channel TolC detected via site-directed disulfide cross-linking. Biochemistry. 2005;44:11115-21 pubmed
    ..The cross-linking was not affected by AcrA, the substrate, or a putative proton coupling site mutation.
  2. Lau S, Zgurskaya H. Cell division defects in Escherichia coli deficient in the multidrug efflux transporter AcrEF-TolC. J Bacteriol. 2005;187:7815-25 pubmed
    ..We found that increased expression of AcrA, the periplasmic membrane fusion protein, is toxic only in cells lacking the multidrug efflux transporter AcrEF...
  3. Yang S, Lopez C, Zechiedrich E. Quorum sensing and multidrug transporters in Escherichia coli. Proc Natl Acad Sci U S A. 2006;103:2386-91 pubmed
    ..These results support a model in which a natural function of AcrAB/TolC and NorE is to export signals for cell-cell communication. Drugs exported by pumps may resemble communication molecules normally exuded. ..
  4. Tikhonova E, Dastidar V, Rybenkov V, Zgurskaya H. Kinetic control of TolC recruitment by multidrug efflux complexes. Proc Natl Acad Sci U S A. 2009;106:16416-21 pubmed publisher
    ..In this study, we reconstituted interactions and compared binding kinetics of the E. coli TolC with AcrA, MacA, and EmrA, the periplasmic MFPs that function in multidrug efflux with transporters from the RND, ABC, and MF ..
  5. Touze T, Eswaran J, Bokma E, Koronakis E, Hughes C, Koronakis V. Interactions underlying assembly of the Escherichia coli AcrAB-TolC multidrug efflux system. Mol Microbiol. 2004;53:697-706 pubmed
    ..Using in vivo cross-linking, we show for the first time that the antiporter AcrB and the adaptor AcrA, which form a translocase in the inner membrane, interact with the outer membrane TolC exit duct to form a ..
  6. Stegmeier J, Polleichtner G, Brandes N, Hotz C, Andersen C. Importance of the adaptor (membrane fusion) protein hairpin domain for the functionality of multidrug efflux pumps. Biochemistry. 2006;45:10303-12 pubmed
    ..tunnel OprM and the Escherichia coli inner membrane complex, formed by adaptor protein (membrane fusion protein) AcrA and transporter AcrB of the resistance nodulation cell division (RND) family, is not functional...
  7. Seeger M, Schiefner A, Eicher T, Verrey F, Diederichs K, Pos K. Structural asymmetry of AcrB trimer suggests a peristaltic pump mechanism. Science. 2006;313:1295-8 pubmed
    The AcrA/AcrB/TolC complex spans the inner and outer membranes of Escherichia coli and serves as its major drug-resistance pump...
  8. Zgurskaya H, Nikaido H. Cross-linked complex between oligomeric periplasmic lipoprotein AcrA and the inner-membrane-associated multidrug efflux pump AcrB from Escherichia coli. J Bacteriol. 2000;182:4264-7 pubmed
    ..AcrB is a proton-motive-force-dependent transporter located in the inner membrane, and AcrA and TolC are accessory proteins located in the periplasm and the outer membrane, respectively...
  9. Higgins M, Bokma E, Koronakis E, Hughes C, Koronakis V. Structure of the periplasmic component of a bacterial drug efflux pump. Proc Natl Acad Sci U S A. 2004;101:9994-9 pubmed publisher
    ..On the basis of the structure and packing, we suggest a model for the key periplasmic interaction between the outer membrane channel and the adaptor protein in the assembled drug efflux pump...

More Information

Publications85

  1. Murakami S, Nakashima R, Yamashita E, Matsumoto T, Yamaguchi A. Crystal structures of a multidrug transporter reveal a functionally rotating mechanism. Nature. 2006;443:173-9 pubmed
    ..in Escherichia coli that cooperates with an outer-membrane channel, TolC, and a membrane-fusion protein, AcrA. Here we describe crystal structures of AcrB with and without substrates...
  2. Lobedanz S, Bokma E, Symmons M, Koronakis E, Hughes C, 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. 2007;104:4612-7 pubmed
    ..Cross-linking of site-specific TolC cysteine variants to wild-type AcrA adaptor identified residues on the lower alpha-helical barrel domain of TolC, defining a contiguous cluster close ..
  3. Augustus A, Celaya T, Husain F, Humbard M, Misra R. Antibiotic-sensitive TolC mutants and their suppressors. J Bacteriol. 2004;186:1851-60 pubmed
    The TolC protein of Escherichia coli, through its interaction with AcrA and AcrB, is thought to form a continuous protein channel that expels inhibitors from the cell. Consequently, tolC null mutations display a hypersensitive phenotype...
  4. Nikaido H, Zgurskaya H. AcrAB and related multidrug efflux pumps of Escherichia coli. J Mol Microbiol Biotechnol. 2001;3:215-8 pubmed
    ..coli is a multidrug efflux system composed of an RND-type transporter AcrB and a periplasmic accessory protein AcrA, and pumps out a wide variety of lipophilic and amphiphilic inhibitors directly into the medium, presumably through ..
  5. Mikolosko J, Bobyk K, Zgurskaya H, Ghosh P. Conformational flexibility in the multidrug efflux system protein AcrA. Structure. 2006;14:577-87 pubmed
    ..which are composed of three essential components as typified by the extensively characterized Escherichia coli AcrA-AcrB-TolC system...
  6. Okusu H, Ma D, Nikaido H. AcrAB efflux pump plays a major role in the antibiotic resistance phenotype of Escherichia coli multiple-antibiotic-resistance (Mar) mutants. J Bacteriol. 1996;178:306-8 pubmed
    ..This experiment identified the AcrAB system as the major pump responsible for making the Mar mutants resistant to many agents, including tetracycline, chloramphenicol, ampicillin, nalidixic acid, and rifampin. ..
  7. Fralick J. Evidence that TolC is required for functioning of the Mar/AcrAB efflux pump of Escherichia coli. J Bacteriol. 1996;178:5803-5 pubmed
    A study examining the influence of TolC on AcrA, AcrR, and MarR1 mutants indicates that functional TolC is required for the operation of the AcrAB efflux system and for the expression of the Mar phenotype...
  8. Fernandez Recio J, Walas F, Federici L, Venkatesh Pratap J, Bavro V, Miguel R, et al. A model of a transmembrane drug-efflux pump from Gram-negative bacteria. FEBS Lett. 2004;578:5-9 pubmed
    ..which is an allosteric channel, the trimeric inner-membrane proton-antiporter AcrB, and the periplasmic protein, AcrA. The pump displaces drugs vectorially from the bacterium using proton electrochemical force...
  9. Yamada S, Awano N, Inubushi K, Maeda E, Nakamori S, Nishino K, et al. Effect of drug transporter genes on cysteine export and overproduction in Escherichia coli. Appl Environ Microbiol. 2006;72:4735-42 pubmed
    ..These results indicate that the multidrug transporter Bcr in the major facilitator family is involved in L-cysteine export and overproduction in genetically engineered E. coli cells. ..
  10. Kincses A, Szabó A, Saijo R, Watanabe G, Kawase M, Molnar J, et al. Fluorinated Beta-diketo Phosphorus Ylides Are Novel Efflux Pump Inhibitors in Bacteria. In Vivo. 2016;30:813-817 pubmed
    ..activity in multidrug efflux pump system consisting of the subunits acridine-resistance proteins A and B (AcrA and AcrB) and the multidrug efflux pump outer membrane factor TolC (TolC) of Escherichia coli K-12 AG100 strain and ..
  11. Ruiz C, Levy S. Regulation of acrAB expression by cellular metabolites in Escherichia coli. J Antimicrob Chemother. 2014;69:390-9 pubmed publisher
    ..A similar induction of acrAB was found when acrA or tolC was deleted, and when the pump function was inhibited using phenylalanine-arginine-?-naphthylamide...
  12. Nikaido H. Multidrug efflux pumps of gram-negative bacteria. J Bacteriol. 1996;178:5853-9 pubmed
  13. Ricci V, Attah V, Overton T, Grainger D, Piddock L. CsrA maximizes expression of the AcrAB multidrug resistance transporter. Nucleic Acids Res. 2017;45:12798-12807 pubmed publisher
    ..Deletion of csrA or mutagenesis of the CsrA binding sites reduced production of both AcrA and AcrB...
  14. Helling R, Janes B, Kimball H, Tran T, Bundesmann M, Check P, et al. Toxic waste disposal in Escherichia coli. J Bacteriol. 2002;184:3699-703 pubmed
    ..The metabolites that accumulate upstream of the blocks caused by the mutations are hypothesized to increase the levels of the AcrAB-TolC pump, thereby removing nalidixic acid from the organism. ..
  15. Nishino K, Yamaguchi A. Role of histone-like protein H-NS in multidrug resistance of Escherichia coli. J Bacteriol. 2004;186:1423-9 pubmed
    ..Double deletion of the mdtEF and acrEF genes completely suppressed Deltahns-mediated multidrug resistance, indicating that Deltahns-mediated multidrug resistance is due to derepression of the acrEF and mdtEF drug exporter genes. ..
  16. Nicoloff H, Perreten V, McMurry L, Levy S. Role for tandem duplication and lon protease in AcrAB-TolC- dependent multiple antibiotic resistance (Mar) in an Escherichia coli mutant without mutations in marRAB or acrRAB. J Bacteriol. 2006;188:4413-23 pubmed
    ..In M113, amplification of acrAB on the duplication led to increased amounts of AcrAB and multidrug resistance. Spontaneous gene duplication represents a new mechanism for mediating multidrug resistance in E. coli through AcrAB-TolC. ..
  17. de Cristóbal R, Vincent P, Salomon R. Multidrug resistance pump AcrAB-TolC is required for high-level, Tet(A)-mediated tetracycline resistance in Escherichia coli. J Antimicrob Chemother. 2006;58:31-6 pubmed
    ..Our results are compatible with the hypothesis that the AcrAB pump is an important component in the development of high levels of resistance to tetracycline in E. coli, perhaps by working in combination with Tet(A). ..
  18. Chai Q, Webb S, Wang Z, Dutch R, Wei Y. Study of the degradation of a multidrug transporter using a non-radioactive pulse chase method. Anal Bioanal Chem. 2016;408:7745-7751 pubmed
    ..efflux in Escherichia coli, the inner membrane transporter AcrB and its functional partner membrane fusion protein AcrA. Together they form a functional complex with an outer membrane channel TolC to actively transport various small ..
  19. Bleuel C, Grosse C, Taudte N, Scherer J, Wesenberg D, Krauss G, et al. TolC is involved in enterobactin efflux across the outer membrane of Escherichia coli. J Bacteriol. 2005;187:6701-7 pubmed
    ..However, iron starvation led to increased expression of the RND gene mdtF and a decrease in acrD. ..
  20. Ip H, Stratton K, Zgurskaya H, Liu J. pH-induced conformational changes of AcrA, the membrane fusion protein of Escherichia coli multidrug efflux system. J Biol Chem. 2003;278:50474-82 pubmed
    The multidrug efflux system AcrA-AcrB-TolC of Escherichia coli expels a wide range of drugs directly into the external medium from the bacterial cell. The mechanism of the efflux process is not fully understood...
  21. Nakamura H. Novel acriflavin resistance genes, acrC and acrD, in Escherichia coli K-12. J Bacteriol. 1979;139:8-12 pubmed
    Acriflavine-resistant mutants were isolated from an acriflavine-sensitive (acrA) strain of Escherichia coli K-12 and then tested for temperature sensitivity of cell division...
  22. Jellen Ritter A, Kern W. Enhanced expression of the multidrug efflux pumps AcrAB and AcrEF associated with insertion element transposition in Escherichia coli mutants Selected with a fluoroquinolone. Antimicrob Agents Chemother. 2001;45:1467-72 pubmed
    ..These observations confirm the importance of efflux-associated nontarget gene mutations and indicate that transposition of genetic elements may have a role in the development of fluoroquinolone resistance in E. coli. ..
  23. Saier M, Tam R, Reizer A, Reizer J. Two novel families of bacterial membrane proteins concerned with nodulation, cell division and transport. Mol Microbiol. 1994;11:841-7 pubmed
    ..We propose that an MFP functions co-operatively with an RND protein to transport large or hydrophobic molecules across the two membranes of the Gram-negative bacterial cell envelope. ..
  24. Eguchi Y, Oshima T, Mori H, Aono R, Yamamoto K, Ishihama A, et al. Transcriptional regulation of drug efflux genes by EvgAS, a two-component system in Escherichia coli. Microbiology. 2003;149:2819-28 pubmed
    A constitutively active mutant of histidine kinase sensor EvgS was found to confer multi-drug resistance (MDR) to an acrA-deficient Escherichia coli, indicating the relationship between the two-component system EvgAS and the expression of ..
  25. Ma D, Cook D, Alberti M, Pon N, Nikaido H, Hearst J. Genes acrA and acrB encode a stress-induced efflux system of Escherichia coli. Mol Microbiol. 1995;16:45-55 pubmed
    Defined mutations of acrA or acrB (formerly acrE) genes increased the susceptibility of Escherichia coli to a range of small inhibitor molecules...
  26. Potrykus J, Barańska S, Wegrzyn G. Inactivation of the acrA gene is partially responsible for chloramphenicol sensitivity of Escherichia coli CM2555 strain expressing the chloramphenicol acetyltransferase gene. Microb Drug Resist. 2002;8:179-85 pubmed
    ..Although no mutation exists in the CM2555 acrE locus, a nonsense mutation in the 67th codon of the acrA gene, which encodes a component of another transmembrane pump, has been found...
  27. Yum S, Xu Y, Piao S, Sim S, Kim H, Jo W, et al. Crystal structure of the periplasmic component of a tripartite macrolide-specific efflux pump. J Mol Biol. 2009;387:1286-97 pubmed publisher
    ..The most characterized MFP AcrA connects the outer membrane factor TolC and the resistance-nodulation-division-type efflux transporter AcrB, which ..
  28. Husain F, Humbard M, Misra R. Interaction between the TolC and AcrA proteins of a multidrug efflux system of Escherichia coli. J Bacteriol. 2004;186:8533-6 pubmed
    ..for physical interactions between the outer membrane component, TolC, and the membrane fusion protein component, AcrA, of the major antibiotic efflux pump of Escherichia coli...
  29. Eicher T, Brandstätter L, Pos K. Structural and functional aspects of the multidrug efflux pump AcrB. Biol Chem. 2009;390:693-9 pubmed publisher
    The tripartite efflux system AcrA/AcrB/TolC is the main pump in Escherichia coli for the efflux of multiple antibiotics, dyes, bile salts and detergents...
  30. Henson J, Walker J. Genetic analysis of acrA and lir mutations of Escherichia coli. J Bacteriol. 1982;152:1301-2 pubmed
    An analysis of acrA (acriflavine- and methylene blue-sensitive) and lir (lincomycin- and erythromycin-sensitive) mutants of Escherichia coli indicated that these mutations are probably within the same gene.
  31. Maira Litran T, Allison D, Gilbert P. An evaluation of the potential of the multiple antibiotic resistance operon (mar) and the multidrug efflux pump acrAB to moderate resistance towards ciprofloxacin in Escherichia coli biofilms. J Antimicrob Chemother. 2000;45:789-95 pubmed
    ..004 mg/L). This protection was again lost at concentrations of 0.1 mg/L. Overall, these results show that ciprofloxacin resistance in biofilms is not mediated by the upregulation of the mar or acrAB operons. ..
  32. Hirakawa H, Nishino K, Yamada J, Hirata T, Yamaguchi A. Beta-lactam resistance modulated by the overexpression of response regulators of two-component signal transduction systems in Escherichia coli. J Antimicrob Chemother. 2003;52:576-82 pubmed
    ..Two-component signal transduction systems contribute to beta-lactam resistance in E. coli. Multidrug exporters play roles in two-component signal transduction system-mediated beta-lactam resistance. ..
  33. Tal N, Schuldiner S. A coordinated network of transporters with overlapping specificities provides a robust survival strategy. Proc Natl Acad Sci U S A. 2009;106:9051-6 pubmed publisher
    ..This strategy also confers evolvability to the organism by reducing constraints on change and allowing the accumulation of nonlethal variation. ..
  34. Nikaido H, Takatsuka Y. Mechanisms of RND multidrug efflux pumps. Biochim Biophys Acta. 2009;1794:769-81 pubmed publisher
    ..Reconstitution of purified AcrB and its relatives showed that the pump is a drug/proton antiporter, that AcrA strongly stimulates the activity of the pump, and that AcrB seems to have a highest affinity for conjugated bile ..
  35. Chen A, Chen Y. [Quantitative competitive RT-PCR and quantitative detection of Escheriia coli acrA-mRNA]. Wei Sheng Wu Xue Bao. 2007;47:235-9 pubmed
    A Quantitative detection assay of acrA-mRNA of Escherichia coli ATCC25922 was developed by Quantitative Competitive RT-PCR. Target Standard(TS) which was same as target-templete acrA was amplified by PCR with P1 and P2 as primers...
  36. Coleman W, Leive L. Two mutations which affect the barrier function of the Escherichia coli K-12 outer membrane. J Bacteriol. 1979;139:899-910 pubmed
    ..One class, given the phenotypic name NbsA, lies at 10 min on the E. coli chromosome...
  37. Potrykus J, Wegrzyn G. The acrAB locus is involved in modulating intracellular acetyl coenzyme A levels in a strain of Escherichia coli CM2555 expressing the chloramphenicol acetyltransferase (cat) gene. Arch Microbiol. 2003;180:362-6 pubmed
    ..This sensitivity was linked to dysfunction of the acrA gene, which encodes a component of the AcrAB-TolC multidrug efflux pump...
  38. Rami A, Toutain C, Jacq A. An increased level of alternative sigma factor RpoS partially suppresses drug hypersensitivity associated with inactivation of the multidrug resistance pump AcrAB in Escherichia coli. Res Microbiol. 2005;156:356-60 pubmed
  39. Baranova N, Nikaido H. 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. 2002;184:4168-76 pubmed
    ..We accordingly propose to rename yegMNOB as mdtABCD (mdt for multidrug transporter). Finally, the expression of two other genes, yicO and ygcL, was shown to be regulated by BaeR, but it is not known if they play any roles in resistance. ..
  40. Kawabe T, Fujihira E, Yamaguchi A. Molecular construction of a multidrug exporter system, AcrAB: molecular interaction between AcrA and AcrB, and cleavage of the N-terminal signal sequence of AcrA. J Biochem. 2000;128:195-200 pubmed
    The AcrAB system of Escherichia coli is an intrinsic efflux protein with a broad substrate specificity. AcrA was thought to be localized in the periplasmic space, and to be linked to AcrB and TolC...
  41. Mazzariol A, Cornaglia G, Nikaido H. Contributions of the AmpC beta-lactamase and the AcrAB multidrug efflux system in intrinsic resistance of Escherichia coli K-12 to beta-lactams. Antimicrob Agents Chemother. 2000;44:1387-90 pubmed
    ..MICs of ureidopenicillins, carbenicillin, oxacillin, and cloxacillin were drastically reduced by the inactivation of AcrAB, whereas those of the earlier cephalosporins were affected mostly by the loss of AmpC beta-lactamase. ..
  42. Chollet R, Chevalier J, Bryskier A, Pages J. The AcrAB-TolC pump is involved in macrolide resistance but not in telithromycin efflux in Enterobacter aerogenes and Escherichia coli. Antimicrob Agents Chemother. 2004;48:3621-4 pubmed
    ..aerogenes acrAB or tolC derivatives compared to that in the parental strain. Two independent efflux pumps, inhibited by phenylalanine arginine beta-naphthylamide, expel macrolides and telithromycin in E. aerogenes...
  43. Qi S, Sukupolvi S, O Connor C. Outer membrane permeability of Escherichia coli K12: isolation, cloning and mapping of suppressors of a defined antibiotic-hypersensitive mutant. Mol Gen Genet. 1991;229:421-7 pubmed
    ..Our results indicate that the sipB locus is located in the 11 min region (485-510 kb) whereas sipC and sipD both map to 82 min (3850-3885 kb)...
  44. Shaheen B, Boothe D, Oyarzabal O, Wang C, Johnson C. Evaluation of the contribution of gyrA mutation and efflux pumps to fluoroquinolone and multidrug resistance in pathogenic Escherichia coli isolates from dogs and cats. Am J Vet Res. 2011;72:25-32 pubmed publisher
  45. Hobbs E, Yin X, Paul B, Astarita J, Storz G. Conserved small protein associates with the multidrug efflux pump AcrB and differentially affects antibiotic resistance. Proc Natl Acad Sci U S A. 2012;109:16696-701 pubmed publisher
    ..Co-purification of AcrZ with AcrB, in the absence of both AcrA and TolC, two-hybrid assays and suppressor mutations indicate that this interaction occurs through the inner ..
  46. Weeks J, Celaya Kolb T, Pecora S, Misra R. AcrA suppressor alterations reverse the drug hypersensitivity phenotype of a TolC mutant by inducing TolC aperture opening. Mol Microbiol. 2010;75:1468-83 pubmed publisher
    ..complex assembly, the periplasmic helices and bottom turns of TolC are thought to interact with a hairpin helix of AcrA and hairpin loops of AcrB respectively...
  47. Oethinger M, Kern W, Jellen Ritter A, McMurry L, Levy S. Ineffectiveness of topoisomerase mutations in mediating clinically significant fluoroquinolone resistance in Escherichia coli in the absence of the AcrAB efflux pump. Antimicrob Agents Chemother. 2000;44:10-3 pubmed
    ..These studies indicate that, in the absence of the AcrAB pump, gyrase mutations fail to produce clinically relevant levels of fluoroquinolone resistance. ..
  48. Andersen C. Channel-tunnels: outer membrane components of type I secretion systems and multidrug efflux pumps of Gram-negative bacteria. Rev Physiol Biochem Pharmacol. 2003;147:122-65 pubmed
    ..Understanding the mechanism of the different export apparatus could help to develop new drugs, which block the efflux pumps or the secretion system. ..
  49. Jones H, Holland I, Jacq A, Wall T, Campbell A. Escherichia coli lacking the AcrAB multidrug efflux pump also lacks nonproteinaceous, PHB-polyphosphate Ca2+ channels in the membrane. Biochim Biophys Acta. 2003;1612:90-7 pubmed
    ..E. coli N43, which lacks the AcrA component of a major multidrug resistance pump, was shown to be defective in calcium handling, with an inability to ..
  50. Nagano K, Nikaido H. Kinetic behavior of the major multidrug efflux pump AcrB of Escherichia coli. Proc Natl Acad Sci U S A. 2009;106:5854-8 pubmed publisher
    ..Here we use intact cells of Escherichia coli containing the intact multiprotein complex AcrB-AcrA-TolC, and measure the kinetic constants for various cephalosporins, by assessing the periplasmic concentration of ..
  51. Avila Sakar A, Misaghi S, Wilson Kubalek E, Downing K, Zgurskaya H, Nikaido H, et al. Lipid-layer crystallization and preliminary three-dimensional structural analysis of AcrA, the periplasmic component of a bacterial multidrug efflux pump. J Struct Biol. 2001;136:81-8 pubmed
    ..We determined a low-resolution (20 A) structure of AcrA, the periplasmic component, by electron crystallography...
  52. Sugawara E, Nikaido H. Properties of AdeABC and AdeIJK efflux systems of Acinetobacter baumannii compared with those of the AcrAB-TolC system of Escherichia coli. Antimicrob Agents Chemother. 2014;58:7250-7 pubmed publisher
    ..These results thus allow us to compare these efflux systems on a quantitative basis, if we can assume that the heterologous systems are fully functional in the E. coli host. ..
  53. Rand J, Danby S, Greenway D, England R. Increased expression of the multidrug efflux genes acrAB occurs during slow growth of Escherichia coli. FEMS Microbiol Lett. 2002;207:91-5 pubmed
    ..Slow growth rate regulation of acrAB transcription does not require the presence of the stationary-phase sigma factor. A putative gearbox consensus sequence was identified at the -10 region of the acrAB promoter. ..
  54. Liu J, Pan Y, Yuan L, Wu H, Hu G, Chen Y. Genetic variations in the active efflux pump genes acrA/B and tolC in different drug-induced strains of Escherichia coli CVCC 1547. Genet Mol Res. 2013;12:2829-36 pubmed publisher
    This study aimed to investigate the properties of mutations of the active efflux pump genes acrA/B and tolC in Escherichia coli CVCC 1547 when induced by different drugs. The mutations were isolated in vitro by exposing E...
  55. Aires J, Nikaido H. Aminoglycosides are captured from both periplasm and cytoplasm by the AcrD multidrug efflux transporter of Escherichia coli. J Bacteriol. 2005;187:1923-9 pubmed
    ..This activity required the presence of AcrA within the proteoliposomes...
  56. Keeney D, Ruzin A, McAleese F, Murphy E, Bradford P. MarA-mediated overexpression of the AcrAB efflux pump results in decreased susceptibility to tigecycline in Escherichia coli. J Antimicrob Chemother. 2008;61:46-53 pubmed
    ..This study suggested that a loss of MarR functionality due to a frameshift mutation resulted in constitutive overproduction of MarA and AcrAB and, consequently, in decreased susceptibility to tigecycline in clinical isolates of E. coli. ..
  57. Stubbings W, Bostock J, Ingham E, Chopra I. Deletion of the multiple-drug efflux pump AcrAB in Escherichia coli prolongs the postantibiotic effect. Antimicrob Agents Chemother. 2005;49:1206-8 pubmed
    ..With specific assays for tetracycline and erythromycin, a direct link between intracellular persistence of antibiotics and maintenance of the PAE was established. ..
  58. Le T, Guet C, Cluzel P. Protein expression enhancement in efflux-deleted mutant bacteria. Protein Expr Purif. 2006;48:28-31 pubmed
    ..We found that the expression level of the green fluorescent protein is several folds higher in DeltaacrAB efflux mutant than in wildtype cells. ..
  59. Gotoh N, Murata T, Ozaki T, Kimura T, Kondo A, Nishino T. Intrinsic resistance of Escherichia coli to mureidomycin A and C due to expression of the multidrug efflux system AcrAB-TolC: comparison with the efflux systems of mureidomycin-susceptible Pseudomonas aeruginosa. J Infect Chemother. 2003;9:101-3 pubmed
    ..These studies showed that the differences regarding the susceptibility of E. coli and P. aeruginosa to mureidomycin A and C may be explained by the expression of efflux systems that mediate resistance to mureidomycin A and C. ..
  60. Bohnert J, Kern W. Selected arylpiperazines are capable of reversing multidrug resistance in Escherichia coli overexpressing RND efflux pumps. Antimicrob Agents Chemother. 2005;49:849-52 pubmed
  61. Kobayashi A, Hirakawa H, Hirata T, Nishino K, Yamaguchi A. Growth phase-dependent expression of drug exporters in Escherichia coli and its contribution to drug tolerance. J Bacteriol. 2006;188:5693-703 pubmed
    ..The induction level was decreased by tnaAB deletion, suggesting that indole sensing stimulates this process. ..
  62. Rieg S, Huth A, Kalbacher H, Kern W. Resistance against antimicrobial peptides is independent of Escherichia coli AcrAB, Pseudomonas aeruginosa MexAB and Staphylococcus aureus NorA efflux pumps. Int J Antimicrob Agents. 2009;33:174-6 pubmed publisher
    ..These findings do not support a critical role of MDR efflux pumps in the tested pathogens as a strategy to increase virulence by circumventing the antimicrobial action of innate defence AMPs. ..
  63. Gerken H, Misra R. Genetic evidence for functional interactions between TolC and AcrA proteins of a major antibiotic efflux pump of Escherichia coli. Mol Microbiol. 2004;54:620-31 pubmed
    Genetic data have suggested that TolC, AcrA and AcrB constitute a major antibiotic efflux system in Escherichia coli...
  64. Rosenberg E, Bertenthal D, Nilles M, Bertrand K, Nikaido H. Bile salts and fatty acids induce the expression of Escherichia coli AcrAB multidrug efflux pump through their interaction with Rob regulatory protein. Mol Microbiol. 2003;48:1609-19 pubmed
    ..Thus, it is likely that E. coli is protecting itself by the Rob-mediated upregulation of AcrAB against the harmful effects of bile salts and fatty acids in the intestinal tract. ..
  65. Tsukagoshi N, Aono R. Entry into and release of solvents by Escherichia coli in an organic-aqueous two-liquid-phase system and substrate specificity of the AcrAB-TolC solvent-extruding pump. J Bacteriol. 2000;182:4803-10 pubmed
    ..The AcrAB-TolC complex likely extrudes solvents with a log P(OW) in the range of 3.4 to 6.0 through a first-order reaction. The most favorable substrates for the efflux system were considered to be octane, heptane, and n-hexane. ..
  66. Bore E, Hebraud M, Chafsey I, Chambon C, Skjaeret C, Moen B, et al. Adapted tolerance to benzalkonium chloride in Escherichia coli K-12 studied by transcriptome and proteome analyses. Microbiology. 2007;153:935-46 pubmed
    ..The results revealed that BC treatment might result in superoxide stress in E. coli. ..
  67. Takatsuka Y, Nikaido H. Covalently linked trimer of the AcrB multidrug efflux pump provides support for the functional rotating mechanism. J Bacteriol. 2009;191:1729-37 pubmed publisher
    ..These observations provide strong biochemical evidence for the functionally rotating mechanism of AcrB pump action. The linked trimer will be useful for further biochemical studies of mechanisms of transport in the future. ..
  68. Paixão L, Rodrigues L, Couto I, Martins M, Fernandes P, de Carvalho C, et al. Fluorometric determination of ethidium bromide efflux kinetics in Escherichia coli. J Biol Eng. 2009;3:18 pubmed publisher
  69. Hirata T, Saito A, Nishino K, Tamura N, Yamaguchi A. Effects of efflux transporter genes on susceptibility of Escherichia coli to tigecycline (GAR-936). Antimicrob Agents Chemother. 2004;48:2179-84 pubmed
    ..coli cells overproducing AcrAB. Therefore, tigecycline is a possible substrate of AcrAB and its close homolog, AcrEF, which are resistance-modulation-division-type multicomponent efflux transporters. ..
  70. Kim H, Xu Y, Lee M, Piao S, Sim S, Ha N, et al. Functional relationships between the AcrA hairpin tip region and the TolC aperture tip region for the formation of the bacterial tripartite efflux pump AcrAB-TolC. J Bacteriol. 2010;192:4498-503 pubmed publisher
    ..that the conserved residues located in the tip region of the alpha-hairpin of the membrane fusion protein (MFP) AcrA play an essential role in the action of the tripartite efflux pump AcrAB-TolC...
  71. Ge Q, Yamada Y, Zgurskaya H. The C-terminal domain of AcrA is essential for the assembly and function of the multidrug efflux pump AcrAB-TolC. J Bacteriol. 2009;191:4365-71 pubmed publisher
    ..In this study, we investigated the structural and functional role of the C-terminal domain of Escherichia coli AcrA, a periplasmic component of the multidrug efflux pump AcrAB-TolC...
  72. Symmons M, Bokma E, Koronakis E, Hughes C, Koronakis V. The assembled structure of a complete tripartite bacterial multidrug efflux pump. Proc Natl Acad Sci U S A. 2009;106:7173-8 pubmed publisher
    ..The completed structure enabled in vivo cross-linking to map intermolecular contacts between the adaptor AcrA and the transporter AcrB, defining a periplasmic interface between several transporter subdomains and the ..
  73. Hirakawa H, Inazumi Y, Masaki T, Hirata T, Yamaguchi A. Indole induces the expression of multidrug exporter genes in Escherichia coli. Mol Microbiol. 2005;55:1113-26 pubmed
    ..BaeR and CpxR directly bound to different sequences of the acrD and mdtA promoter regions. These observations indicate that BaeR is a primary regulator, and CpxR enhances the effect of BaeR. ..
  74. White D, Goldman J, Demple B, Levy S. Role of the acrAB locus in organic solvent tolerance mediated by expression of marA, soxS, or robA in Escherichia coli. J Bacteriol. 1997;179:6122-6 pubmed
    ..These findings strongly suggest that active efflux specified by the acrAB locus is linked to intrinsic organic solvent tolerance and to tolerance mediated by the marA, soxS, or robA gene product in E. coli. ..
  75. Thanassi D, Cheng L, Nikaido H. Active efflux of bile salts by Escherichia coli. J Bacteriol. 1997;179:2512-8 pubmed
    ..an important role, since the accumulation level of chenodeoxycholate increased strongly upon deenergization of acrA emrB double mutant cells...
  76. Krishnamoorthy G, Tikhonova E, Zgurskaya H. Fitting periplasmic membrane fusion proteins to inner membrane transporters: mutations that enable Escherichia coli AcrA to function with Pseudomonas aeruginosa MexB. J Bacteriol. 2008;190:691-8 pubmed
    AcrAB-TolC from Escherichia coli is a multidrug efflux complex capable of transenvelope transport. In this complex, AcrA is a periplasmic membrane fusion protein that establishes a functional connection between the inner membrane ..