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1 Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA
2 Microbial Genetics Group, School of Biological Sciences, University of Sussex, Falmer, Brighton BN1 9QG, UK
3 Division of Biological Sciences, University of Montana, Missoula, MT 59812-1002, USA
4 Laboratories of Microbial Pathogenesis, Medical Research Service, VA Medical Center (Atlanta), Decatur, GA 30033, USA
ABSTRACT
Summary: The mtr (multiple transferable resistance) system of Neisseria gonorrhoeae determines levels of gonococcal resistance to hydrophobic agents (HAs), including detergent-like fatty acids and bile salts that bathe certain mucosal surfaces. The genetic organization of the mtr system was determined and found to consist of the mtrR gene, which encodes a transcriptional regulator (MtrR), and three tandemly linked genes termed mtrCDE. The mtrCDE genes were organized in the same apparent transcriptional unit, upstream and divergent from the mtrR gene. The mtrCDE-encoded proteins of N. gonorrhoeae were analogous to a family of bacterial efflux/transport proteins, notably the MexABOprK proteins of Pseudomonas aeruginosa and the AcrAE and EnvCD proteins of Escherichia coli, that mediate resistance to drugs, dyes, and detergents. Inactivation of the mtrC gene resulted in loss of the MtrC lipoprotein and rendered gonococci hypersusceptible to structurally diverse HAs; this revealed the importance of the mtr system in determining HAR in gonococci. Further support for a role of the mtrCDE gene complex in determining levels of HAR in gonococci was evident when transformants bearing mutations in the mtrR gene were analysed. In this respect, missense and null mutations in the mtrR gene were found to result in increased levels of MtrC and HAR. However, high levels of MtrC and HAR, similar to those observed for clinical isolates, were associated with a single bp deletion in a 13 bp inverted repeat sequence that intervened the divergent mtrR and mtrC genes. We propose that the 13 bp inverted-repeat sequence represents a transcriptional control element that regulates expression of the mtrRCDE gene complex, thereby modulating levels of gonococcal susceptibility to HAs.
5Tel: +1 404 728 7688. Fax: +1 404 329 2210. e-mail: wshafer@unix.cc.emory.edu
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W. L. Veal, R. A. Nicholas, and W. M. Shafer Overexpression of the MtrC-MtrD-MtrE Efflux Pump Due to an mtrR Mutation Is Required for Chromosomally Mediated Penicillin Resistance in Neisseria gonorrhoeae J. Bacteriol., October 15, 2002; 184(20): 5619 - 5624. [Abstract] [Full Text] [PDF]
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P. A. Ropp, M. Hu, M. Olesky, and R. A. Nicholas Mutations in ponA, the Gene Encoding Penicillin-Binding Protein 1, and a Novel Locus, penC, Are Required for High-Level Chromosomally Mediated Penicillin Resistance in Neisseria gonorrhoeae Antimicrob. Agents Chemother., March 1, 2002; 46(3): 769 - 777. [Abstract] [Full Text] [PDF]
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C. Rouquette-Loughlin, I. Stojiljkovic, T. Hrobowski, J. T. Balthazar, and W. M. Shafer Inducible, but Not Constitutive, Resistance of Gonococci to Hydrophobic Agents Due to the MtrC-MtrD-MtrE Efflux Pump Requires TonB-ExbB-ExbD Proteins Antimicrob. Agents Chemother., February 1, 2002; 46(2): 561 - 565. [Abstract] [Full Text] [PDF]
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S. Magnet, P. Courvalin, and T. Lambert Resistance-Nodulation-Cell Division-Type Efflux Pump Involved in Aminoglycoside Resistance in Acinetobacter baumannii Strain BM4454 Antimicrob. Agents Chemother., December 1, 2001; 45(12): 3375 - 3380. [Abstract] [Full Text] [PDF]
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K. Tsuge, Y. Ohata, and M. Shoda Gene yerP, Involved in Surfactin Self-Resistance in Bacillus subtilis Antimicrob. Agents Chemother., December 1, 2001; 45(12): 3566 - 3573. [Abstract] [Full Text] [PDF]
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P. Godoy, M. I. Ramos-Gonzalez, and J. L. Ramos Involvement of the TonB System in Tolerance to Solvents and Drugs in Pseudomonas putida DOT-T1E J. Bacteriol., September 15, 2001; 183(18): 5285 - 5292. [Abstract] [Full Text] [PDF]
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L. Zarantonelli, G. Borthagaray, E. H. Lee, W. Veal, and W. M. Shafer Decreased susceptibility to azithromycin and erythromycin mediated by a novel mtr(R) promoter mutation in Neisseria gonorrhoeae J. Antimicrob. Chemother., May 1, 2001; 47(5): 651 - 654. [Abstract] [Full Text] [PDF]
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L. A. S. Snyder, N. J. Saunders, and W. M. Shafer A Putatively Phase Variable Gene (dca) Required for Natural Competence in Neisseria gonorrhoeae but Not Neisseria meningitidis Is Located within the Division Cell Wall (dcw) Gene Cluster J. Bacteriol., February 15, 2001; 183(4): 1233 - 1241. [Abstract] [Full Text]
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O. F. Join-Lambert, M. Michéa-Hamzehpour, T. Köhler, F. Chau, F. Faurisson, S. Dautrey, C. Vissuzaine, C. Carbon, and J.-C. Pechère Differential Selection of Multidrug Efflux Mutants by Trovafloxacin and Ciprofloxacin in an Experimental Model of Pseudomonas aeruginosa Acute Pneumonia in Rats Antimicrob. Agents Chemother., February 1, 2001; 45(2): 571 - 576. [Abstract] [Full Text]
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B. Vester and S. Douthwaite Macrolide Resistance Conferred by Base Substitutions in 23S rRNA Antimicrob. Agents Chemother., January 1, 2001; 45(1): 1 - 12. [Full Text]
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M. Putman, H. W. van Veen, and W. N. Konings Molecular Properties of Bacterial Multidrug Transporters Microbiol. Mol. Biol. Rev., December 1, 2000; 64(4): 672 - 693. [Abstract] [Full Text] [PDF]
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K. Poole Efflux-Mediated Resistance to Fluoroquinolones in Gram-Negative Bacteria Antimicrob. Agents Chemother., September 1, 2000; 44(9): 2233 - 2241. [Full Text]
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J. E. Bina, R. A. Alm, M. Uria-Nickelsen, S. R. Thomas, T. J. Trust, and R. E. W. Hancock Helicobacter pylori Uptake and Efflux: Basis for Intrinsic Susceptibility to Antibiotics In Vitro Antimicrob. Agents Chemother., February 1, 2000; 44(2): 248 - 254. [Abstract] [Full Text]
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J. R. Aires, T. Köhler, H. Nikaido, and P. Plésiat Involvement of an Active Efflux System in the Natural Resistance of Pseudomonas aeruginosa to Aminoglycosides Antimicrob. Agents Chemother., November 1, 1999; 43(11): 2624 - 2628. [Abstract] [Full Text]
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L. Zarantonelli, G. Borthagaray, E.-H. Lee, and W. M. Shafer Decreased Azithromycin Susceptibility of Neisseria gonorrhoeae Due to mtrR Mutations Antimicrob. Agents Chemother., October 1, 1999; 43(10): 2468 - 2472. [Abstract] [Full Text]
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R. A. Moore, D. DeShazer, S. Reckseidler, A. Weissman, and D. E. Woods Efflux-Mediated Aminoglycoside and Macrolide Resistance in Burkholderia pseudomallei Antimicrob. Agents Chemother., March 1, 1999; 43(3): 465 - 470. [Abstract] [Full Text]
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N. Masuda, N. Gotoh, C. Ishii, E. Sakagawa, S. Ohya, and T. Nishino Interplay between Chromosomal beta -Lactamase and the MexAB-OprM Efflux System in Intrinsic Resistance to beta -Lactams in Pseudomonas aeruginosa Antimicrob. Agents Chemother., February 1, 1999; 43(2): 400 - 402. [Abstract] [Full Text]
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M. J. Gill, S. Simjee, K. Al-Hattawi, B. D. Robertson, C. S. F. Easmon, and C. A. Ison Gonococcal Resistance to beta -Lactams and Tetracycline Involves Mutation in Loop 3 of the Porin Encoded at the penB Locus Antimicrob. Agents Chemother., November 1, 1998; 42(11): 2799 - 2803. [Abstract] [Full Text]
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C. A. Ison, P. J. Woodford, H. Madders, and E. Claydon Drift in Susceptibility of Neisseria gonorrhoeae to Ciprofloxacin and Emergence of Therapeutic Failure Antimicrob. Agents Chemother., November 1, 1998; 42(11): 2919 - 2922. [Abstract] [Full Text]
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K. Evans, L. Passador, R. Srikumar, E. Tsang, J. Nezezon, and K. Poole Influence of the MexAB-OprM Multidrug Efflux System on Quorum Sensing in Pseudomonas aeruginosa J. Bacteriol., October 15, 1998; 180(20): 5443 - 5447. [Abstract] [Full Text]
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S. Grkovic, M. H. Brown, N. J. Roberts, I. T. Paulsen, and R. A. Skurray QacR Is a Repressor Protein That Regulates Expression of the Staphylococcus aureus Multidrug Efflux Pump QacA J. Biol. Chem., July 17, 1998; 273(29): 18665 - 18673. [Abstract] [Full Text] [PDF]
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 W. M. Shafer, X.-D. Qu, A. J. Waring, and R. I. Lehrer Modulation of Neisseria gonorrhoeae susceptibility to vertebrate antibacterial peptides due to a member of the resistance/nodulation/division efflux pump family PNAS, February 17, 1998; 95(4): 1829 - 1833. [Abstract] [Full Text] [PDF]
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R. Srikumar, T. Kon, N. Gotoh, and K. Poole Expression of Pseudomonas aeruginosa Multidrug Efflux Pumps MexA-MexB-OprM and MexC-MexD-OprJ in a Multidrug-Sensitive Escherichia coli Strain Antimicrob. Agents Chemother., January 1, 1998; 42(1): 65 - 71. [Abstract] [Full Text]
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