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Gene Review

D786_p068  -  efflux pump

Pseudomonas resinovorans

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Disease relevance of ORF178


High impact information on ORF178

  • Heavy metal resistance in the mutants could be correlated by quantitative real time PCR with increased expression of the heavy metal efflux pump CzcCBA and its cognate two-component regulator genes czcR-czcS [6].
  • The effect of cio mutation on Deltap-dependent accumulation of chloramphenicol suggested that antibiotic sensitivity resulted from loss of or damage to a multidrug efflux pump [7].
  • These results clearly demonstrated that the resistance-nodulation-division-type efflux pump in P. aeruginosa selects and transports substrates via the domains that largely protrude over the cytoplasmic membrane [8].
  • Function of the membrane fusion protein, MexA, of the MexA, B-OprM efflux pump in Pseudomonas aeruginosa without an anchoring membrane [9].
  • AmpC and OprD are not involved in the mechanism of imipenem hypersusceptibility among Pseudomonas aeruginosa isolates overexpressing the mexCD-oprJ efflux pump [10].

Chemical compound and disease context of ORF178


Biological context of ORF178


Anatomical context of ORF178

  • Resistance in these P. aeruginosa strains could depend not only on DNA-gyrase modifications but also on membranes alterations and on the presence (qualitative and quantitative) of the efflux pump formed by three subunits [21].

Associations of ORF178 with chemical compounds

  • The mutation that has been referred to previously as nfxC expresses an additional efflux pump, MexEF-OprN, exhibiting resistance to fluoroquinolones, imipenem, and chloramphenicol and hypersusceptibility to beta-lactam antibiotics [19].
  • While meropenem MICs were strongly influenced by the presence or absence of the MexAB-OprM efflux pump in both OprD-proficient and -deficient strain backgrounds, MICs of imipenem and of ER-35786 remained unchanged, demonstrating that meropenem is a substrate of MexAB-OprM but not imipenem and ER-35786 [22].
  • Ciprofloxacin resistance by P. aeruginosa is mediated in part by an efflux pump mechanism [23].
  • One representative carbenicillin-resistant strain overexpressed OprM, the outer membrane channel component of the MexAB-OprM efflux pump [24].
  • To do so, we studied the effects of the divalent cations Mg(2+) and Ca(2+) on susceptibility to aminoglycosides in a wild-type strain of P. aeruginosa and in mutants either overexpressing or lacking the MexXY-OprM efflux pump [25].

Analytical, diagnostic and therapeutic context of ORF178


  1. Mechanisms of solvent tolerance in gram-negative bacteria. Ramos, J.L., Duque, E., Gallegos, M.T., Godoy, P., Ramos-Gonzalez, M.I., Rojas, A., Teran, W., Segura, A. Annu. Rev. Microbiol. (2002) [Pubmed]
  2. Localization of the outer membrane subunit OprM of resistance-nodulation-cell division family multicomponent efflux pump in Pseudomonas aeruginosa. Nakajima, A., Sugimoto, Y., Yoneyama, H., Nakae, T. J. Biol. Chem. (2000) [Pubmed]
  3. Mechanisms of fluoroquinolone resistance: an update 1994-1998. Piddock, L.J. Drugs (1999) [Pubmed]
  4. Inducible, but not constitutive, resistance of gonococci to hydrophobic agents due to the MtrC-MtrD-MtrE efflux pump requires TonB-ExbB-ExbD proteins. Rouquette-Loughlin, C., Stojiljkovic, I., Hrobowski, T., Balthazar, J.T., Shafer, W.M. Antimicrob. Agents Chemother. (2002) [Pubmed]
  5. Fluoroquinolone resistance of Serratia marcescens: involvement of a proton gradient-dependent efflux pump. Kumar, A., Worobec, E.A. J. Antimicrob. Chemother. (2002) [Pubmed]
  6. CzcR-CzcS, a two-component system involved in heavy metal and carbapenem resistance in Pseudomonas aeruginosa. Perron, K., Caille, O., Rossier, C., Van Delden, C., Dumas, J.L., Köhler, T. J. Biol. Chem. (2004) [Pubmed]
  7. Mutation or overexpression of a terminal oxidase leads to a cell division defect and multiple antibiotic sensitivity in Pseudomonas aeruginosa. Tavankar, G.R., Mossialos, D., Williams, H.D. J. Biol. Chem. (2003) [Pubmed]
  8. An elegant means of self-protection in gram-negative bacteria by recognizing and extruding xenobiotics from the periplasmic space. Eda, S., Maseda, H., Nakae, T. J. Biol. Chem. (2003) [Pubmed]
  9. Function of the membrane fusion protein, MexA, of the MexA, B-OprM efflux pump in Pseudomonas aeruginosa without an anchoring membrane. Yoneyama, H., Maseda, H., Kamiguchi, H., Nakae, T. J. Biol. Chem. (2000) [Pubmed]
  10. AmpC and OprD are not involved in the mechanism of imipenem hypersusceptibility among Pseudomonas aeruginosa isolates overexpressing the mexCD-oprJ efflux pump. Wolter, D.J., Hanson, N.D., Lister, P.D. Antimicrob. Agents Chemother. (2005) [Pubmed]
  11. Enhancement of the mexAB-oprM efflux pump expression by a quorum-sensing autoinducer and its cancellation by a regulator, MexT, of the mexEF-oprN efflux pump operon in Pseudomonas aeruginosa. Maseda, H., Sawada, I., Saito, K., Uchiyama, H., Nakae, T., Nomura, N. Antimicrob. Agents Chemother. (2004) [Pubmed]
  12. Antibiotic resistance caused by gram-negative multidrug efflux pumps. Nikaido, H. Clin. Infect. Dis. (1998) [Pubmed]
  13. The MexJK efflux pump of Pseudomonas aeruginosa requires OprM for antibiotic efflux but not for efflux of triclosan. Chuanchuen, R., Narasaki, C.T., Schweizer, H.P. J. Bacteriol. (2002) [Pubmed]
  14. Spread of efflux pump-overexpressing, non-metallo-beta-lactamase-producing, meropenem-resistant but ceftazidime-susceptible Pseudomonas aeruginosa in a region with blaVIM endemicity. Pournaras, S., Maniati, M., Spanakis, N., Ikonomidis, A., Tassios, P.T., Tsakris, A., Legakis, N.J., Maniatis, A.N. J. Antimicrob. Chemother. (2005) [Pubmed]
  15. Characterization of a new efflux pump, MexGHI-OpmD, from Pseudomonas aeruginosa that confers resistance to vanadium. Aendekerk, S., Ghysels, B., Cornelis, P., Baysse, C. Microbiology (Reading, Engl.) (2002) [Pubmed]
  16. Nucleotide sequence analysis of a gene from Burkholderia (Pseudomonas) cepacia encoding an outer membrane lipoprotein involved in multiple antibiotic resistance. Burns, J.L., Wadsworth, C.D., Barry, J.J., Goodall, C.P. Antimicrob. Agents Chemother. (1996) [Pubmed]
  17. Resistance to beta-lactam antibiotics in Pseudomonas aeruginosa due to interplay between the MexAB-OprM efflux pump and beta-lactamase. Nakae, T., Nakajima, A., Ono, T., Saito, K., Yoneyama, H. Antimicrob. Agents Chemother. (1999) [Pubmed]
  18. Amino acid residues essential for function of the MexF efflux pump protein of Pseudomonas aeruginosa. Aires, J.R., Pechère, J.C., Van Delden, C., Köhler, T. Antimicrob. Agents Chemother. (2002) [Pubmed]
  19. Assignment of the substrate-selective subunits of the MexEF-OprN multidrug efflux pump of Pseudomonas aeruginosa. Maseda, H., Yoneyama, H., Nakae, T. Antimicrob. Agents Chemother. (2000) [Pubmed]
  20. Function of the MexB efflux-transporter divided into two halves. Eda, S., Yoneyama, H., Nakae, T. Biochemistry (2003) [Pubmed]
  21. Molecular mechanisms of resistance in Pseudomonas aeruginosa to fluoroquinolones. Speciale, A., Musumeci, R., Blandino, G., Caccamo, F., Siracusa, V., Renis, M. Int. J. Antimicrob. Agents (2000) [Pubmed]
  22. Carbapenem activities against Pseudomonas aeruginosa: respective contributions of OprD and efflux systems. Köhler, T., Michea-Hamzehpour, M., Epp, S.F., Pechere, J.C. Antimicrob. Agents Chemother. (1999) [Pubmed]
  23. In vitro synergy of ciprofloxacin and gatifloxacin against ciprofloxacin-resistant Pseudomonas aeruginosa. Pankey, G.A., Ashcraft, D.S. Antimicrob. Agents Chemother. (2005) [Pubmed]
  24. Efflux-mediated resistance to tigecycline (GAR-936) in Pseudomonas aeruginosa PAO1. Dean, C.R., Visalli, M.A., Projan, S.J., Sum, P.E., Bradford, P.A. Antimicrob. Agents Chemother. (2003) [Pubmed]
  25. MexXY-OprM efflux pump is required for antagonism of aminoglycosides by divalent cations in Pseudomonas aeruginosa. Mao, W., Warren, M.S., Lee, A., Mistry, A., Lomovskaya, O. Antimicrob. Agents Chemother. (2001) [Pubmed]
  26. Single live cell imaging of chromosomes in chloramphenicol-induced filamentous Pseudomonas aeruginosa. Steel, C., Wan, Q., Xu, X.H. Biochemistry (2004) [Pubmed]
  27. Expression of Pseudomonas aeruginosa multidrug efflux pumps MexA-MexB-OprM and MexC-MexD-OprJ in a multidrug-sensitive Escherichia coli strain. Srikumar, R., Kon, T., Gotoh, N., Poole, K. Antimicrob. Agents Chemother. (1998) [Pubmed]
  28. Large outbreak in a surgical intensive care unit of colonization or infection with Pseudomonas aeruginosa that overexpressed an active efflux pump. Bertrand, X., Bailly, P., Blasco, G., Balvay, P., Boillot, A., Talon, D. Clin. Infect. Dis. (2000) [Pubmed]
  29. Linkage of the efflux-pump expression level with substrate extrusion rate in the MexAB-OprM efflux pump of Pseudomonas aeruginosa. Narita, S., Eda, S., Yoshihara, E., Nakae, T. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
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