Multidrug efflux pumps as main players in intrinsic and acquired resistance to antimicrobials

Drug Resistance Updates

Volumn 28, Issue , 2016, Pages 13-27

  Hernando Amado, Sara ^a   Blanco, Paula ^a   Alcalde Rico, Manuel ^a   Corona, Fernando ^a   Reales Calderón, Jose A ^a   Sánchez, María B ^a   Martínez, José L ^a  

^a CENTRO NACIONAL DE BIOTECNOLOGÍA   (Spain)

Author keywords

Antibiotic resistance; Bacterial virulence; Multidrug efflux pumps; Resistance to antifungals

Indexed keywords

ANTIBIOTIC AGENT; ANTIFUNGAL AGENT; ANTIINFECTIVE AGENT; BACTERIAL PROTEIN; FUNGAL PROTEIN;

ANTIBIOTIC RESISTANCE; ANTIFUNGAL RESISTANCE; GRAM NEGATIVE BACTERIUM; GRAM POSITIVE BACTERIUM; MULTIDRUG EFFLUX PUMP; NONHUMAN; PRIORITY JOURNAL; REVIEW; ANTAGONISTS AND INHIBITORS; BACTERIAL INFECTION; DRUG EFFECTS; FUNGUS; GENE; GENE EXPRESSION REGULATION; GENETICS; GROWTH, DEVELOPMENT AND AGING; HUMAN; METABOLISM; MICROBIOLOGY; MULTIDRUG RESISTANCE; MYCOSIS;

ANTI-INFECTIVE AGENTS; BACTERIAL INFECTIONS; BACTERIAL PROTEINS; DRUG RESISTANCE, MULTIPLE, BACTERIAL; DRUG RESISTANCE, MULTIPLE, FUNGAL; FUNGAL PROTEINS; FUNGI; GENE EXPRESSION REGULATION, BACTERIAL; GENE EXPRESSION REGULATION, FUNGAL; GENES, MDR; GRAM-NEGATIVE BACTERIA; GRAM-POSITIVE BACTERIA; HUMANS; MYCOSES;

EID: 84978152942     PISSN: 13687646     EISSN: 15322084     Source Type: Journal    
DOI: 10.1016/j.drup.2016.06.007     Document Type: Review

References (193)

1. Adam, Y., Tayer, N., Rotem, D., Schreiber, G., Schuldiner, S., The fast release of sticky protons: kinetics of substrate binding and proton release in a multidrug transporter. Proc. Natl. Acad. Sci. U. S. A. 104 (2007), 17989–17994.
2. Alonso, A., Martinez, J.L., Cloning and characterization of SmeDEF, a novel multidrug efflux pump from Stenotrophomonas maltophilia. Antimicrob. Agents Chemother. 44 (2000), 3079–3086.
3. Alonso, A., Martinez, J.L., Expression of multidrug efflux pump SmeDEF by clinical isolates of Stenotrophomonas maltophilia. Antimicrob. Agents Chemother. 45 (2001), 1879–1881.
4. Alvarez-Ortega, C., Olivares, J., Martínez, J.L., RND multidrug efflux pumps: what are they good for?. Front. Microbiol., 4, 2013, 7.
5. Arkin, I.T., Russ, W.P., Lebendiker, M., Schuldiner, S., Determining the secondary structure and orientation of EmrE, a multi-drug transporter, indicates a transmembrane four-helix bundle. Biochemistry 35 (1996), 7233–7238.
6. Balasubramanian, D., Schneper, L., Merighi, M., Smith, R., Narasimhan, G., Lory, S., Mathee, K., The regulatory repertoire of Pseudomonas aeruginosa AmpC ss-lactamase regulator AmpR includes virulence genes. PLoS ONE, 7, 2012, e34067.
7. Baquero, F., Low-level antibacterial resistance: a gateway to clinical resistance. Drug Resist. Updat. 4 (2001), 93–105.
8. Baquero, F., Low-level antibiotic resistance. Hughes, D., Andersson, D.I., (eds.) Antibiotics Development and Resistance, 2001, Taylor & Francis Books Ltd., London, 117–136.
9. Barchiesi, F., Calabrese, D., Sanglard, D., Falconi Di Francesco, L., Caselli, F., Giannini, D., Giacometti, A., Gavaudan, S., Scalise, G., Experimental induction of fluconazole resistance in Candida tropicalis ATCC 750. Antimicrob. Agents Chemother. 44 (2000), 1578–1584.
10. Baucheron, S., Imberechts, H., Chaslus-Dancla, E., Cloeckaert, A., The AcrB multidrug transporter plays a major role in high-level fluoroquinolone resistance in Salmonella enterica serovar typhimurium phage type DT204. Microb. Drug Resist. 8 (2002), 281–289.
11. Birukou, I., Tonthat, N.K., Seo, S.M., Schindler, B.D., Kaatz, G.W., Brennan, R.G., The molecular mechanisms of allosteric mutations impairing MepR repressor function in multidrug-resistant strains of Staphylococcus aureus. MBio, 4, 2013 e00528-00513.
12. Blair, J.M., Bavro, V.N., Ricci, V., Modi, N., Cacciotto, P., Kleinekathfer, U., Ruggerone, P., Vargiu, A.V., Baylay, A.J., Smith, H.E., Brandon, Y., Galloway, D., Piddock, L.J., AcrB drug-binding pocket substitution confers clinically relevant resistance and altered substrate specificity. Proc. Natl. Acad. Sci. U. S. A. 112 (2015), 3511–3516.
13. Blair, J.M., Richmond, G.E., Piddock, L.J., Multidrug efflux pumps in Gram-negative bacteria and their role in antibiotic resistance. Future Microbiol. 9 (2014), 1165–1177.
14. Bolla, J.R., Do, S.V., Long, F., Dai, L., Su, C.C., Lei, H.T., Chen, X., Gerkey, J.E., Murphy, D.C., Rajashankar, K.R., Zhang, Q., Yu, E.W., Structural and functional analysis of the transcriptional regulator Rv3066 of Mycobacterium tuberculosis. Nucleic Acids Res. 40 (2012), 9340–9355.
15. Calabrese, D., Bille, J., Sanglard, D., A novel multidrug efflux transporter gene of the major facilitator superfamily from Candida albicans (FLU1) conferring resistance to fluconazole. Microbiology 146:Pt 11 (2000), 2743–2754.
16. Chambers, H.F., Deleo, F.R., Waves of resistance: Staphylococcus aureus in the antibiotic era. Nat. Rev. Microbiol. 7 (2009), 629–641.
17. Chang, L.L., Chen, H.F., Chang, C.Y., Lee, T.M., Wu, W.J., Contribution of integrons, and SmeABC and SmeDEF efflux pumps to multidrug resistance in clinical isolates of Stenotrophomonas maltophilia. J. Antimicrob. Chemother. 53 (2004), 518–521.
18. Chang, T.Y., Huang, B.J., Sun, J.R., Perng, C.L., Chan, M.C., Yu, C.P., Chiueh, T.S., AdeR protein regulates adeABC expression by binding to a direct-repeat motif in the intercistronic spacer. Microbiol. Res. 183 (2016), 60–67.
19. Chen, H., Hu, J., Chen, P.R., Lan, L., Li, Z., Hicks, L.M., Dinner, A.R., He, C., The Pseudomonas aeruginosa multidrug efflux regulator MexR uses an oxidation-sensing mechanism. Proc. Natl. Acad. Sci. U. S. A. 105 (2008), 13586–13591.
20. Chouchani, C., El Salabi, A., Marrakchi, R., Ferchichi, L., Walsh, T.R., First report of mefA and msrA/msrB multidrug efflux pumps associated with blaTEM-1 beta-lactamase in Enterococcus faecalis. Int. J. Infect. Dis. 16 (2012), e104–e109.
21. Correa, J.E., De Paulis, A., Predari, S., Sordelli, D.O., Jeric, P.E., First report of qacG, qacH and qacJ genes in Staphylococcus haemolyticus human clinical isolates. J. Antimicrob. Chemother. 62 (2008), 956–960.
22. Costa, S.S., Viveiros, M., Amaral, L., Couto, I., Multidrug efflux pumps in Staphylococcus aureus: an update. Open Microbiol. J. 7 (2013), 59–71.
23. Coste, A.T., Karababa, M., Ischer, F., Bille, J., Sanglard, D., TAC1, transcriptional activator of CDR genes, is a new transcription factor involved in the regulation of Candida albicans ABC transporters CDR1 and CDR2. Eukaryot. Cell 3 (2004), 1639–1652.
24. Cox, G., Wright, G.D., Intrinsic antibiotic resistance: mechanisms, origins, challenges and solutions. Int. J. Med. Microbiol. 303 (2013), 287–292.
25. Coyne, S., Courvalin, P., Perichon, B., Efflux-mediated antibiotic resistance in Acinetobacter spp. Antimicrob. Agents Chemother. 55 (2011), 947–953.
26. Daly, M.M., Doktor, S., Flamm, R., Shortridge, D., Characterization and prevalence of MefA, MefE, and the associated msr(D) gene in Streptococcus pneumoniae clinical isolates. J. Clin. Microbiol. 42 (2004), 3570–3574.
27. Daury, L., Orange, F., Taveau, J.C., Verchere, A., Monlezun, L., Gounou, C., Marreddy, R.K., Picard, M., Broutin, I., Pos, K.M., Lambert, O., Tripartite assembly of RND multidrug efflux pumps. Nat. Commun., 7, 2016, 10731.
28. Davis, D.R., McAlpine, J.B., Pazoles, C.J., Talbot, M.K., Alder, E.A., White, C., Jonas, B.M., Murray, B.E., Weinstock, G.M., Rogers, B.L., Enterococcus faecalis multi-drug resistance transporters: application for antibiotic discovery. J. Mol. Microbiol. Biotechnol. 3 (2001), 179–184.
29. Dawson, R.J., Locher, K.P., Structure of a bacterial multidrug ABC transporter. Nature 443 (2006), 180–185.
30. De Groote, M.A., Huitt, G., Infections due to rapidly growing mycobacteria. Clin. Infect. Dis. 42 (2006), 1756–1763.
31. Deng, M., Zhu, M.H., Li, J.J., Bi, S., Sheng, Z.K., Hu, F.S., Zhang, J.J., Chen, W., Xue, X.W., Sheng, J.F., Li, L.J., Molecular epidemiology and mechanisms of tigecycline resistance in clinical isolates of Acinetobacter baumannii from a Chinese university hospital. Antimicrob. Agents Chemother. 58 (2014), 297–303.
32. Du, D., van Veen, H.W., Murakami, S., Pos, K.M., Luisi, B.F., Structure, mechanism and cooperation of bacterial multidrug transporters. Curr. Opin. Struct. Biol. 33 (2015), 76–91.
33. Du, D., Wang, Z., James, N.R., Voss, J.E., Klimont, E., Ohene-Agyei, T., Venter, H., Chiu, W., Luisi, B.F., Structure of the AcrAB-TolC multidrug efflux pump. Nature 509 (2014), 512–515.
34. Dunkel, N., Blass, J., Rogers, P.D., Morschhauser, J., Mutations in the multi-drug resistance regulator MRR1, followed by loss of heterozygosity, are the main cause of MDR1 overexpression in fluconazole-resistant Candida albicans strains. Mol. Microbiol. 69 (2008), 827–840.
35. Eicher, T., Seeger, M.A., Anselmi, C., Zhou, W., Brandstatter, L., Verrey, F., Diederichs, K., Faraldo-Gomez, J.D., Pos, K.M., Coupling of remote alternating-access transport mechanisms for protons and substrates in the multidrug efflux pump AcrB. eLife, 3, 2014.
36. Esteban, J., Martin-de-Hijas, N.Z., Ortiz, A., Kinnari, T.J., Bodas Sanchez, A., Gadea, I., Fernandez-Roblas, R., Detection of lfrA and tap efflux pump genes among clinical isolates of non-pigmented rapidly growing mycobacteria. Int. J. Antimicrob. Agents 34 (2009), 454–456.
37. Fajardo, A., Martinez-Martin, N., Mercadillo, M., Galan, J.C., Ghysels, B., Matthijs, S., Cornelis, P., Wiehlmann, L., Tummler, B., Baquero, F., Martinez, J.L., The neglected intrinsic resistome of bacterial pathogens. PLoS ONE, 3, 2008, e1619.
38. Fernando, D., Zhanel, G., Kumar, A., Antibiotic resistance and expression of resistance-nodulation-division pump- and outer membrane porin-encoding genes in Acinetobacter species isolated from Canadian hospitals. Can. J. Infect. Dis. Med. Microbiol. 24 (2013), 17–21.
39. Ferrari, S., Ischer, F., Calabrese, D., Posteraro, B., Sanguinetti, M., Fadda, G., Rohde, B., Bauser, C., Bader, O., Sanglard, D., Gain of function mutations in CgPDR1 of Candida glabrata not only mediate antifungal resistance but also enhance virulence. PLoS Pathog., 5, 2009.
40. Fetar, H., Gilmour, C., Klinoski, R., Daigle, D.M., Dean, C.R., Poole, K., mexEF-oprN multidrug efflux operon of Pseudomonas aeruginosa: regulation by the MexT activator in response to nitrosative stress and chloramphenicol. Antimicrob. Agents Chemother. 55 (2011), 508–514.
41. Fiedler, S., Bender, J.K., Klare, I., Halbedel, S., Grohmann, E., Szewzyk, U., Werner, G., Tigecycline resistance in clinical isolates of Enterococcus faecium is mediated by an upregulation of plasmid-encoded tetracycline determinants tet(L) and tet(M). J. Antimicrob. Chemother. 71 (2016), 871–881.
42. Garcia-Leon, G., Hernandez, A., Hernando-Amado, S., Alavi, P., Berg, G., Martinez, J.L., A function of SmeDEF, the major quinolone resistance determinant of Stenotrophomonas maltophilia, is the colonization of plant roots. Appl. Environ. Microbiol. 80 (2014), 4559–4565.
43. Garcia-Leon, G., Ruiz de Alegria Puig, C., Garcia de la Fuente, C., Martinez-Martinez, L., Martinez, J.L., Sanchez, M.B., High-level quinolone resistance is associated with the overexpression of smeVWX in Stenotrophomonas maltophilia clinical isolates. Clin. Microbiol. Infect. 21 (2015), 464–467.
44. Garcia-Leon, G., Salgado, F., Oliveros, J.C., Sanchez, M.B., Martinez, J.L., Interplay between intrinsic and acquired resistance to quinolones in Stenotrophomonas maltophilia. Environ. Microbiol. 16 (2014), 1282–1296.
45. Garvey, M.I., Baylay, A.J., Wong, R.L., Piddock, L.J., Overexpression of patA and patB, which encode ABC transporters, is associated with fluoroquinolone resistance in clinical isolates of Streptococcus pneumoniae. Antimicrob. Agents Chemother. 55 (2011), 190–196.
46. Gaur, M., Puri, N., Manoharlal, R., Rai, V., Mukhopadhayay, G., Choudhury, D., Prasad, R., MFS transportome of the human pathogenic yeast Candida albicans. BMC Genomics, 9, 2008.
47. Gayen, A., Leninger, M., Traaseth, N.J., Protonation of a glutamate residue modulates the dynamics of the drug transporter EmrE. Nat. Chem. Biol., 2016.
48. Gbelska, Y., Krijger, J.J., Breunig, K.D., Evolution of gene families: the multidrug resistance transporter genes in five related yeast species. FEMS Yeast Res. 6 (2006), 345–355.
49. Godreuil, S., Galimand, M., Gerbaud, G., Jacquet, C., Courvalin, P., Efflux pump Lde is associated with fluoroquinolone resistance in Listeria monocytogenes. Antimicrob. Agents Chemother. 47 (2003), 704–708.
50. Golparian, D., Shafer, W.M., Ohnishi, M., Unemo, M., Importance of multidrug efflux pumps in the antimicrobial resistance property of clinical multidrug-resistant isolates of Neisseria gonorrhoeae. Antimicrob. Agents Chemother. 58 (2014), 3556–3559.
51. Grinnage-Pulley, T., Zhang, Q., Genetic basis and functional consequences of differential expression of the CmeABC efflux pump in Campylobacter jejuni isolates. PLOS ONE, 10, 2015, e0131534.
52. Grkovic, S., Brown, M.H., Schumacher, M.A., Brennan, R.G., Skurray, R.A., The staphylococcal QacR multidrug regulator binds a correctly spaced operator as a pair of dimers. J. Bacteriol. 183 (2001), 7102–7109.
53. Grkovic, S., Brown, M.H., Skurray, R.A., Transcriptional regulation of multidrug efflux pumps in bacteria. Semin. Cell Dev. Biol. 12 (2001), 225–237.
54. Grkovic, S., Hardie, K.M., Brown, M.H., Skurray, R.A., Interactions of the QacR multidrug-binding protein with structurally diverse ligands: implications for the evolution of the binding pocket. Biochemistry 42 (2003), 15226–15236.
55. Guerin, F., Galimand, M., Tuambilangana, F., Courvalin, P., Cattoir, V., Overexpression of the novel MATE fluoroquinolone efflux pump FepA in Listeria monocytogenes is driven by inactivation of its local repressor FepR. PLOS ONE, 9, 2014, e106340.
56. Gupta, A.K., Chauhan, D.S., Srivastava, K., Das, R., Batra, S., Mittal, M., Goswami, P., Singhal, N., Sharma, V.D., Venkatesan, K., Hasnain, S.E., Katoch, V.M., Estimation of efflux mediated multi-drug resistance and its correlation with expression levels of two major efflux pumps in mycobacteria. J. Commun. Dis. 38 (2006), 246–254.
57. He, F., Fu, Y., Chen, Q., Ruan, Z., Hua, X., Zhou, H., Yu, Y., Tigecycline susceptibility and the role of efflux pumps in tigecycline resistance in KPC-producing Klebsiella pneumoniae. PLOS ONE, 10, 2015, e0119064.
58. He, X., Szewczyk, P., Karyakin, A., Evin, M., Hong, W.X., Zhang, Q., Chang, G., Structure of a cation-bound multidrug and toxic compound extrusion transporter. Nature 467 (2010), 991–994.
59. Hernandez, A., Ruiz, F.M., Romero, A., Martinez, J.L., The binding of triclosan to SmeT, the repressor of the multidrug efflux pump SmeDEF, induces antibiotic resistance in Stenotrophomonas maltophilia. PLoS Pathog., 7, 2011, e1002103.
60. Hidalgo, E., Leautaud, V., Demple, B., The redox-regulated SoxR protein acts from a single DNA site as a repressor and an allosteric activator. EMBO J. 17 (1998), 2629–2636.
61. Hobbs, E.C., Yin, X., Paul, B.J., Astarita, J.L., Storz, G., Conserved small protein associates with the multidrug efflux pump AcrB and differentially affects antibiotic resistance. Proc. Natl. Acad. Sci. U. S. A. 109 (2012), 16696–16701.
62. Hocquet, D., Muller, A., Blanc, K., Plesiat, P., Talon, D., Monnet, D.L., Bertrand, X., Relationship between antibiotic use and incidence of MexXY-OprM overproducers among clinical isolates of Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 52 (2008), 1173–1175.
63. Hocquet, D., Vogne, C., El Garch, F., Vejux, A., Gotoh, N., Lee, A., Lomovskaya, O., Plesiat, P., MexXY-OprM efflux pump is necessary for a adaptive resistance of Pseudomonas aeruginosa to aminoglycosides. Antimicrob. Agents Chemother. 47 (2003), 1371–1375.
64. Horiyama, T., Nishino, K., AcrB, AcrD, and MdtABC multidrug efflux systems are involved in enterobactin export in Escherichia coli. PLOS ONE, 9, 2014, e108642.
65. Hornsey, M., Ellington, M.J., Doumith, M., Scott, G., Livermore, D.M., Woodford, N., Emergence of AcrAB-mediated tigecycline resistance in a clinical isolate of Enterobacter cloacae during ciprofloxacin treatment. Int. J. Antimicrob. Agents 35 (2010), 478–481.
66. Huang, M., McClellan, M., Berman, J., Kao, K.C., Evolutionary dynamics of Candida albicans during in vitro evolution. Eukaryot. Cell 10 (2011), 1413–1421.
67. Jang, S., Multidrug efflux pumps in Staphylococcus aureus and their clinical implications. J. Microbiol. (Seoul, Korea) 54 (2016), 1–8.
68. Jeannot, K., Sobel, M.L., El Garch, F., Poole, K., Plesiat, P., Induction of the MexXY efflux pump in Pseudomonas aeruginosa is dependent on drug–ribosome interaction. J. Bacteriol. 187 (2005), 5341–5346.
69. Jeon, B., Wang, Y., Hao, H., Barton, Y.W., Zhang, Q., Contribution of CmeG to antibiotic and oxidative stress resistance in Campylobacter jejuni. J. Antimicrob. Chemother. 66 (2011), 79–85.
70. Jerse, A.E., Sharma, N.D., Simms, A.N., Crow, E.T., Snyder, L.A., Shafer, W.M., A gonococcal efflux pump system enhances bacterial survival in a female mouse model of genital tract infection. Infect. Immun. 71 (2003), 5576–5582.
71. Jia, W., Li, G., Wang, W., Prevalence and antimicrobial resistance of Enterococcus species: a hospital-based study in China. Int. J. Environ. Res. Public Health 11 (2014), 3424–3442.
72. Jonas, B.M., Murray, B.E., Weinstock, G.M., Characterization of emeA, a NorA homolog and multidrug resistance efflux pump, in Enterococcus faecalis. Antimicrob. Agents Chemother. 45 (2001), 3574–3579.
73. Kaatz, G.W., DeMarco, C.E., Seo, S.M., MepR, a repressor of the Staphylococcus aureus MATE family multidrug efflux pump MepA, is a substrate-responsive regulatory protein. Antimicrob. Agents Chemother. 50 (2006), 1276–1281.
74. Kao, C.Y., Chen, C.A., Liu, Y.F., Wu, H.M., Chiou, C.S., Yan, J.J., Wu, J.J., Molecular characterization of antimicrobial susceptibility of Salmonella isolates: first identification of a plasmid carrying qnrD or oqxAB in Taiwan. J. Microbiol. Immunol. Infect. = Wei Mian Yu Gan Ran Za Zhi, 2015.
75. Kim, J.S., Jeong, H., Song, S., Kim, H.Y., Lee, K., Hyun, J., Ha, N.C., Structure of the tripartite multidrug efflux pump AcrAB-TolC suggests an alternative assembly mode. Mol. Cells 38 (2015), 180–186.
76. Kobayashi, N., Nishino, K., Yamaguchi, A., Novel macrolide-specific ABC-type efflux transporter in Escherichia coli. J. Bacteriol. 183 (2001), 5639–5644.
77. Kong, K.-F., Jayawardena, S.R., Indulkar, S.D., del Puerto, A., Koh, C.-L., Hoiby, N., Mathee, K., Pseudomonas aeruginosa AmpR is a global transcriptional factor that regulates expression of AmpC and PoxB beta-lactamases, proteases, quorum sensing, and other virulence factors. Antimicrob. Agents Chemother. 49 (2005), 4567–4575.
78. Kvist, M., Hancock, V., Klemm, P., Inactivation of efflux pumps abolishes bacterial biofilm formation. Appl. Environ. Microbiol. 74 (2008), 7376–7382.
79. Kwak, Y.G., Truong-Bolduc, Q.C., Bin Kim, H., Song, K.H., Kim, E.S., Hooper, D.C., Association of norB overexpression and fluoroquinolone resistance in clinical isolates of Staphylococcus aureus from Korea. J. Antimicrob. Chemother. 68 (2013), 2766–2772.
80. Lamping, E., Baret, P.V., Holmes, A.R., Monk, B.C., Goffeau, A., Cannon, R.D., Fungal PDR transporters: phylogeny, topology, motifs and function. Fungal Genet. Biol. 47 (2010), 127–142.
81. Lau, C.H., Krahn, T., Gilmour, C., Mullen, E., Poole, K., AmgRS-mediated envelope stress-inducible expression of the mexXY multidrug efflux operon of Pseudomonas aeruginosa. Microbiology Open 4 (2015), 121–135.
82. Law, C.J., Maloney, P.C., Wang, D.N., Ins and outs of major facilitator superfamily antiporters. Annu. Rev. Microbiol. 62 (2008), 289–305.
83. Lee, E.H., Rouquette-Loughlin, C., Folster, J.P., Shafer, W.M., FarR regulates the farAB-encoded efflux pump of Neisseria gonorrhoeae via an MtrR regulatory mechanism. J. Bacteriol. 185 (2003), 7145–7152.
84. Lee, E.H., Shafer, W.M., The farAB-encoded efflux pump mediates resistance of gonococci to long-chained antibacterial fatty acids. Mol. Microbiol. 33 (1999), 839–845.
85. Lee, E.W., Huda, M.N., Kuroda, T., Mizushima, T., Tsuchiya, T., EfrAB, an ABC multidrug efflux pump in Enterococcus faecalis. Antimicrob. Agents Chemother. 47 (2003), 3733–3738.
86. Li, G., Zhang, J., Guo, Q., Jiang, Y., Wei, J., Zhao, L.L., Zhao, X., Lu, J., Wan, K., Efflux pump gene expression in multidrug-resistant Mycobacterium tuberculosis clinical isolates. PLOS ONE, 10, 2015, e0119013.
87. Li, X.-Z., Plésiat, P., Nikaido, H., The challenge of efflux-mediated antibiotic resistance in Gram-negative bacteria. Clin. Microbiol. Rev. 28 (2015), 337–418.
88. Li, X.Z., Livermore, D.M., Nikaido, H., Role of efflux pump(s) in intrinsic resistance of Pseudomonas aeruginosa: resistance to tetracycline, chloramphenicol, and norfloxacin. Antimicrob. Agents Chemother. 38 (1994), 1732–1741.
89. Li, X.Z., Nikaido, H., Efflux-mediated drug resistance in bacteria: an update. Drugs 69 (2009), 1555–1623.
90. Li, X.Z., Plesiat, P., Nikaido, H., The challenge of efflux-mediated antibiotic resistance in Gram-negative bacteria. Clin. Microbiol. Rev. 28 (2015), 337–418.
91. Lin, J., Cagliero, C., Guo, B., Barton, Y.W., Maurel, M.C., Payot, S., Zhang, Q., Bile salts modulate expression of the CmeABC multidrug efflux pump in Campylobacter jejuni. J. Bacteriol. 187 (2005), 7417–7424.
92. Lin, M.F., Lin, Y.Y., Yeh, H.W., Lan, C.Y., Role of the BaeSR two-component system in the regulation of Acinetobacter baumannii adeAB genes and its correlation with tigecycline susceptibility. BMC Microbiol., 14, 2014, 119.
93. Lin, Y.T., Huang, Y.W., Chen, S.J., Chang, C.W., Yang, T.C., The SmeYZ efflux pump of Stenotrophomonas maltophilia contributes to drug resistance, virulence-related characteristics, and virulence in mice. Antimicrob. Agents Chemother. 59 (2015), 4067–4073.
94. Lin, Y.T., Huang, Y.W., Liou, R.S., Chang, Y.C., Yang, T.C., MacABCsm, an ABC-type tripartite efflux pump of Stenotrophomonas maltophilia involved in drug resistance, oxidative and envelope stress tolerances and biofilm formation. J. Antimicrob. Chemother. 69 (2014), 3221–3226.
95. Llanes, C., Hocquet, D., Vogne, C., Benali-Baitich, D., Neuwirth, C., Plesiat, P., Clinical strains of Pseudomonas aeruginosa overproducing MexAB-OprM and MexXY efflux pumps simultaneously. Antimicrob. Agents Chemother. 48 (2004), 1797–1802.
96. Lomonaco, S., Nucera, D., Filipello, V., The evolution and epidemiology of Listeria monocytogenes in Europe and the United States. Infect. Genet. Evol. 35 (2015), 172–183.
97. Lomovskaya, O., Lee, A., Hoshino, K., Ishida, H., Mistry, A., Warren, M.S., Boyer, E., Chamberland, S., Lee, V.J., Use of a genetic approach to evaluate the consequences of inhibition of efflux pumps in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 43 (1999), 1340–1346.
98. Lu, M., Structures of multidrug and toxic compound extrusion transporters and their mechanistic implications. Channels (Austin), 2015, 1–13.
99. Lu, M., Radchenko, M., Symersky, J., Nie, R., Guo, Y., Structural insights into H+-coupled multidrug extrusion by a MATE transporter. Nat. Struct. Mol. Biol. 20 (2013), 1310–1317.
100. Lu, T.L., Cao, Y., Zhou, L.X., Huang, M.J., Xu, X., Pei, X.F., The antimicrobial resistance analysis of 73 strains of Streptococcus pneumoniae isolated from infant respiratory tract. Sichuan da Xue Xue Bao Yi Xue Ban = J. Sichuan Univ. Med. Sci. Ed. 46 (2015), 417–421.
101. Lu, Z., Chen, Y., Chen, W., Liu, H., Song, Q., Hu, X., Zou, Z., Liu, Z., Duo, L., Yang, J., Gong, Y., Wang, Z., Wu, X., Zhao, J., Zhang, C., Zhang, M., Han, L., Characteristics of qacA/B-positive Staphylococcus aureus isolated from patients and a hospital environment in China. J. Antimicrob. Chemother. 70 (2015), 653–657.
102. Lucas, C.E., Balthazar, J.T., Hagman, K.E., Shafer, W.M., The MtrR repressor binds the DNA sequence between the mtrR and mtrC genes of Neisseria gonorrhoeae. J. Bacteriol. 179 (1997), 4123–4128.
103. Ma, D., Alberti, M., Lynch, C., Nikaido, H., Hearst, J.E., The local repressor AcrR plays a modulating role in the regulation of acrAB genes of Escherichia coli by global stress signals. Mol. Microbiol. 19 (1996), 101–112.
104. Martinez, J.L., The antibiotic resistome: challenge and opportunity for therapeutic intervention. Future Med. Chem. 4 (2012), 347–359.
105. Martinez, J.L., Coque, T.M., Baquero, F., What is a resistance gene? Ranking risk in resistomes. Nat. Rev. Microbiol. 13 (2015), 116–123.
106. Martinez, J.L., Sanchez, M.B., Martinez-Solano, L., Hernandez, A., Garmendia, L., Fajardo, A., Alvarez-Ortega, C., Functional role of bacterial multidrug efflux pumps in microbial natural ecosystems. FEMS Microbiol. Rev. 33 (2009), 430–449.
107. Maseda, H., Sawada, I., Saito, K., Uchiyama, H., Nakae, T., Nomura, N., 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. Antimicrob. Agents Chemother. 48 (2004), 1320–1328.
108. Mata, M.T., Baquero, F., Perez-Diaz, J.C., A multidrug efflux transporter in Listeria monocytogenes. FEMS Microbiol. Lett. 187 (2000), 185–188.
109. Matsuo, Y., Eda, S., Gotoh, N., Yoshihara, E., Nakae, T., MexZ-mediated regulation of mexXY multidrug efflux pump expression in Pseudomonas aeruginosa by binding on the mexZ-mexX intergenic DNA. FEMS Microbiol. Lett. 238 (2004), 23–28.
110. Mayer, S., Boos, M., Beyer, A., Fluit, A.C., Schmitz, F.J., Distribution of the antiseptic resistance genes qacA, qacB and qacC in 497 methicillin-resistant and -susceptible European isolates of Staphylococcus aureus. J. Antimicrob. Chemother. 47 (2001), 896–897.
111. McGann, P., Kwak, Y.I., Summers, A., Cummings, J.F., Waterman, P.E., Lesho, E.P., Detection of qacA/B in clinical isolates of methicillin-resistant Staphylococcus aureus from a regional healthcare network in the eastern United States. Infect. Control Hosp. Epidemiol. 32 (2011), 1116–1119.
112. McMurry, L., Petrucci, R.E. Jr., Levy, S.B., Active efflux of tetracycline encoded by four genetically different tetracycline resistance determinants in Escherichia coli. Proc. Natl. Acad. Sci. U. S. A. 77 (1980), 3974–3977.
113. Mercante, A.D., Jackson, L., Johnson, P.J., Stringer, V.A., Dyer, D.W., Shafer, W.M., MpeR regulates the mtr efflux locus in Neisseria gonorrhoeae and modulates antimicrobial resistance by an iron-responsive mechanism. Antimicrob. Agents Chemother. 56 (2012), 1491–1501.
114. Morimyo, M., Hongo, E., Hama-Inaba, H., Machida, I., Cloning and characterization of the mvrC gene of Escherichia coli K-12 which confers resistance against methyl viologen toxicity. Nucleic Acids Res. 20 (1992), 3159–3165.
115. Morita, Y., Kimura, N., Mima, T., Mizushima, T., Tsuchiya, T., Roles of MexXY- and MexAB-multidrug efflux pumps in intrinsic multidrug resistance of Pseudomonas aeruginosa PAO1. J. Gen. Appl. Microbiol. 47 (2001), 27–32.
116. Morita, Y., Murata, T., Mima, T., Shiota, S., Kuroda, T., Mizushima, T., Gotoh, N., Nishino, T., Tsuchiya, T., Induction of mexCD-oprJ operon for a multidrug efflux pump by disinfectants in wild-type Pseudomonas aeruginosa PAO1. J. Antimicrob. Chemother. 51 (2003), 991–994.
117. Morrison, E.A., DeKoster, G.T., Dutta, S., Vafabakhsh, R., Clarkson, M.W., Bahl, A., Kern, D., Ha, T., Henzler-Wildman, K.A., Antiparallel EmrE exports drugs by exchanging between asymmetric structures. Nature 481 (2012), 45–50.
118. Muller, C., Plesiat, P., Jeannot, K., A two-component regulatory system interconnects resistance to polymyxins, aminoglycosides, fluoroquinolones, and beta-lactams in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 55 (2011), 1211–1221.
119. Murakami, S., Nakashima, R., Yamashita, E., Matsumoto, T., Yamaguchi, A., Crystal structures of a multidrug transporter reveal a functionally rotating mechanism. Nature 443 (2006), 173–179.
120. Nascimento, A.M., Goldman, G.H., Park, S., Marras, S.A.E., Delmas, G., Oza, U., Lolans, K., Dudley, M.N., Mann, P.A., Perlin, D.S., Multiple resistance mechanisms among Aspergillus fumigatus mutants with high-level resistance to itraconazole. Antimicrob. Agents Chemother. 47 (2003), 1719–1726.
121. Niimi, K., Maki, K., Ikeda, F., Holmes, A.R., Lamping, E., Niimi, M., Monk, B.C., Cannon, R.D., Overexpression of Candida albicans CDR1, CDR2, or MDR1 does not produce significant changes in echinocandin susceptibility. Antimicrob. Agents Chemother. 50 (2006), 1148–1155.
122. Nikaido, E., Shirosaka, I., Yamaguchi, A., Nishino, K., Regulation of the AcrAB multidrug efflux pump in Salmonella enterica serovar Typhimurium in response to indole and paraquat. Microbiology 157 (2011), 648–655.
123. Nikaido, H., Multidrug resistance in bacteria. Annu. Rev. Biochem. 78 (2009), 119–146.
124. Nishino, K., Yamaguchi, A., Analysis of a complete library of putative drug transporter genes in Escherichia coli. J. Bacteriol. 183 (2001), 5803–5812.
125. 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. 178 (1996), 306–308.
126. Olivares, J., Bernardini, A., Garcia-Leon, G., Corona, F., B.S. M., Martinez, J.L., The intrinsic resistome of bacterial pathogens. Front. Microbiol., 4, 2013, 103.
127. Pamp, S.J., Gjermansen, M., Johansen, H.K., Tolker-Nielsen, T., Tolerance to the antimicrobial peptide colistin in Pseudomonas aeruginosa biofilms is linked to metabolically active cells, and depends on the pmr and mexAB-oprM genes. Mol. Microbiol. 68 (2008), 223–240.
128. Parker, A., Gottesman, S., Small RNA regulation of TolC, the outer membrane component of bacterial multidrug transporters. J. Bacteriol. 198 (2016), 1101–1113.
129. Patel, D., Kosmidis, C., Seo, S.M., Kaatz, G.W., Ethidium bromide MIC screening for enhanced efflux pump gene expression or efflux activity in Staphylococcus aureus. Antimicrob. Agents Chemother. 54 (2010), 5070–5073.
130. Paul, S., Alegre, K.O., Holdsworth, S.R., Rice, M., Brown, J.A., McVeigh, P., Kelly, S.M., Law, C.J., A single-component multidrug transporter of the major facilitator superfamily is part of a network that protects Escherichia coli from bile salt stress. Mol. Microbiol. 92 (2014), 872–884.
131. Piddock, L.J., Clinically relevant chromosomally encoded multidrug resistance efflux pumps in bacteria. Clin. Microbiol. Rev. 19 (2006), 382–402.
132. Piddock, L.J., Multidrug-resistance efflux pumps – not just for resistance. Nat. Rev. Microbiol. 4 (2006), 629–636.
133. Piddock, L.J., Johnson, M.M., Accumulation of 10 fluoroquinolones by wild-type or efflux mutant Streptococcus pneumoniae. Antimicrob. Agents Chemother. 46 (2002), 813–820.
134. Piddock, L.J., Johnson, M.M., Simjee, S., Pumbwe, L., Expression of efflux pump gene pmrA in fluoroquinolone-resistant and -susceptible clinical isolates of Streptococcus pneumoniae. Antimicrob. Agents Chemother. 46 (2002), 808–812.
135. Poole, K., Gotoh, N., Tsujimoto, H., Zhao, Q., Wada, A., Yamasaki, T., Neshat, S., Yamagishi, J., Li, X.Z., Nishino, T., Overexpression of the mexC-mexD-oprJ efflux operon in nfxB-type multidrug-resistant strains of Pseudomonas aeruginosa. Mol. Microbiol. 21 (1996), 713–724.
136. Pos, K.M., Drug transport mechanism of the AcrB efflux pump. Biochim. Biophys. Acta 1794 (2009), 782–793.
137. Prasad, R., Dewergifosse, P., Goffeau, A., Balzi, E., Molecular-cloning and characterization of a novel gene of Candida-albicans, Cdr1, conferring multiple resistance to drugs and antifungals. Curr. Genet. 27 (1995), 320–329.
138. Pumbwe, L., Randall, L.P., Woodward, M.J., Piddock, L.J., Expression of the efflux pump genes cmeB, cmeF and the porin gene porA in multiple-antibiotic-resistant Campylobacter jejuni. J. Antimicrob. Chemother. 54 (2004), 341–347.
139. Purssell, A., Fruci, M., Mikalauskas, A., Gilmour, C., Poole, K., EsrC, an envelope stress-regulated repressor of the mexCD-oprJ multidrug efflux operon in Pseudomonas aeruginosa. Environ. Microbiol. 17 (2015), 186–198.
140. Rahmati, S., Yang, S., Davidson, A.L., Zechiedrich, E.L., Control of the AcrAB multidrug efflux pump by quorum-sensing regulator SdiA. Mol. Microbiol. 43 (2002), 677–685.
141. Ramon-Garcia, S., Martin, C., Thompson, C.J., Ainsa, J.A., Role of the Mycobacterium tuberculosis P55 efflux pump in intrinsic drug resistance, oxidative stress responses, and growth. Antimicrob. Agents Chemother. 53 (2009), 3675–3682.
142. Ramon-Garcia, S., Mick, V., Dainese, E., Martin, C., Thompson, C.J., De Rossi, E., Manganelli, R., Ainsa, J.A., Functional and genetic characterization of the tap efflux pump in Mycobacterium bovis BCG. Antimicrob. Agents Chemother. 56 (2012), 2074–2083.
143. Reeves, A.Z., Campbell, P.J., Sultana, R., Malik, S., Murray, M., Plikaytis, B.B., Shinnick, T.M., Posey, J.E., Aminoglycoside cross-resistance in Mycobacterium tuberculosis due to mutations in the 5′ untranslated region of whiB7. Antimicrob. Agents Chemother. 57 (2013), 1857–1865.
144. Ribera, A., Domenech-Sanchez, A., Ruiz, J., Benedi, V.J., Jimenez de Anta, M.T., Vila, J., Mutations in gyrA and parC QRDRs are not relevant for quinolone resistance in epidemiological unrelated Stenotrophomonas maltophilia clinical isolates. Microb. Drug Resist. 8 (2002), 245–251.
145. Richardot, C., Juarez, P., Jeannot, K., Patry, I., Plesiat, P., Llanes, C., Amino acid substitutions account for most MexS alterations in clinical nfxC mutants of Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 60 (2016), 2302–2310.
146. Romanova, N.A., Wolffs, P.F., Brovko, L.Y., Griffiths, M.W., Role of efflux pumps in adaptation and resistance of Listeria monocytogenes to benzalkonium chloride. Appl. Environ. Microbiol. 72 (2006), 3498–3503.
147. Rosenberg, E.Y., Bertenthal, D., Nilles, M.L., Bertrand, K.P., 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. 48 (2003), 1609–1619.
148. Sanchez, M.B., Antibiotic resistance in the opportunistic pathogen Stenotrophomonas maltophilia. Front. Microbiol., 6, 2015, 658.
149. Sanchez, P., Alonso, A., Martinez, J.L., Cloning and characterization of SmeT, a repressor of the Stenotrophomonas maltophilia multidrug efflux pump SmeDEF. Antimicrob. Agents Chemother. 46 (2002), 3386–3393.
150. Sanglard, D., Kuchler, K., Ischer, F., Pagani, J.L., Monod, M., Bille, J., Mechanisms of resistance to azole antifungal agents in Candida-albicans isolates from aids patients involve specific multidrug transporters. Antimicrob. Agents Chemother. 39 (1995), 2378–2386.
151. Sato, T., Yokota, S., Okubo, T., Ishihara, K., Ueno, H., Muramatsu, Y., Fujii, N., Tamura, Y., Contribution of the AcrAB-TolC efflux pump to high-level fluoroquinolone resistance in Escherichia coli isolated from dogs and humans. J. Vet. Med. Sci./Jpn. Soc. Vet. Sci. 75 (2013), 407–414.
152. Sato, T., Yokota, S., Uchida, I., Okubo, T., Usui, M., Kusumoto, M., Akiba, M., Fujii, N., Tamura, Y., Fluoroquinolone resistance mechanisms in an Escherichia coli isolate, HUE1, without quinolone resistance-determining region mutations. Front. Microbiol., 4, 2013, 125.
153. Schmalstieg, A.M., Srivastava, S., Belkaya, S., Deshpande, D., Meek, C., Leff, R., van Oers, N.S., Gumbo, T., The antibiotic resistance arrow of time: efflux pump induction is a general first step in the evolution of mycobacterial drug resistance. Antimicrob. Agents Chemother. 56 (2012), 4806–4815.
154. Schmitz, F.J., Sadurski, R., Kray, A., Boos, M., Geisel, R., Kohrer, K., Verhoef, J., Fluit, A.C., Prevalence of macrolide-resistance genes in Staphylococcus aureus and Enterococcus faecium isolates from 24 European university hospitals. J. Antimicrob. Chemother. 45 (2000), 891–894.
155. Schuldiner, S., EmrE, a model for studying evolution and mechanism of ion-coupled transporters. Biochim. Biophys. Acta 1794 (2009), 748–762.
156. Seeger, M.A., Schiefner, A., Eicher, T., Verrey, F., Diederichs, K., Pos, K.M., Structural asymmetry of AcrB trimer suggests a peristaltic pump mechanism. Science 313 (2006), 1295–1298.
157. Siddiqi, N., Das, R., Pathak, N., Banerjee, S., Ahmed, N., Katoch, V.M., Hasnain, S.E., Mycobacterium tuberculosis isolate with a distinct genomic identity overexpresses a tap-like efflux pump. Infection 32 (2004), 109–111.
158. Siikala, E., Rautemaa, R., Richardson, M., Saxen, H., Bowyer, P., Sanglard, D., Persistent Candida albicans colonization and molecular mechanisms of azole resistance in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) patients. J. Antimicrob. Chemother. 65 (2010), 2505–2513.
159. Singh, K.V., Murray, B.E., Differences in the Enterococcus faecalis lsa locus that influence susceptibility to quinupristin-dalfopristin and clindamycin. Antimicrob. Agents Chemother. 49 (2005), 32–39.
160. Srinivasan, V.B., Rajamohan, G., KpnEF, a new member of the Klebsiella pneumoniae cell envelope stress response regulon, is an SMR-type efflux pump involved in broad-spectrum antimicrobial resistance. Antimicrob. Agents Chemother. 57 (2013), 4449–4462.
161. Srinivasan, V.B., Singh, B.B., Priyadarshi, N., Chauhan, N.K., Rajamohan, G., Role of novel multidrug efflux pump involved in drug resistance in Klebsiella pneumoniae. PLOS ONE, 9, 2014, e96288.
162. Stavri, M., Piddock, L.J., Gibbons, S., Bacterial efflux pump inhibitors from natural sources. J. Antimicrob. Chemother. 59 (2007), 1247–1260.
163. Stover, C.K., Pham, X.Q., Erwin, A.L., Mizoguchi, S.D., Warrener, P., Hickey, M.J., Brinkman, F.S.L., Hufnagle, W.O., Kowalik, D.J., Lagrou, M., Garber, R.L., Goltry, L., Tolentino, E., Westbrock-Wadman, S., Yuan, Y., Brody, L.L., Coulter, S.N., Folger, K.R., Kas, A., Larbig, K., Lim, R., Smith, K., Spencer, D., Wong, G.K.-S., Wu, Z., Paulsen, I.T., Reizer, J., Saier, M.H., Hancock, R.E.W., Lory, S., Olson, M.V., Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen. Nature 406 (2000), 959–964.
164. Sugimura, M., Maseda, H., Hanaki, H., Nakae, T., Macrolide antibiotic-mediated downregulation of MexAB-OprM efflux pump expression in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 52 (2008), 4141–4144.
165. Sulavik, M.C., Gambino, L.F., Miller, P.F., The MarR repressor of the multiple antibiotic resistance (mar) operon in Escherichia coli: prototypic member of a family of bacterial regulatory proteins involved in sensing phenolic compounds. Mol. Med. (Cambridge, Mass.) 1 (1995), 436–446.
166. Sun, Z., Xu, Y., Sun, Y., Liu, Y., Zhang, X., Huang, H., Li, C., Ofloxacin resistance in Mycobacterium tuberculosis is associated with efflux pump activity independent of resistance pattern and genotype. Microb. Drug Resist. 20 (2014), 525–532.
167. Symmons, M.F., 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. 106 (2009), 7173–7178.
168. Tanabe, M., Szakonyi, G., Brown, K.A., Henderson, P.J., Nield, J., Byrne, B., The multidrug resistance efflux complex, EmrAB from Escherichia coli forms a dimer in vitro. Biochem. Biophys. Res. Commun. 380 (2009), 338–342.
169. Theodoulou, F.L., Kerr, I.D., ABC transporter research: going strong 40 years on. Biochem. Soc. Trans. 43 (2015), 1033–1040.
170. Tikhonova, E.B., Devroy, V.K., Lau, S.Y., 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.
171. Trepout, S., Taveau, J.C., Benabdelhak, H., Granier, T., Ducruix, A., Frangakis, A.S., Lambert, O., Structure of reconstituted bacterial membrane efflux pump by cryo-electron tomography. Biochim. Biophys. Acta 1798 (2010), 1953–1960.
172. Unemo, M., Shafer, W.M., Antimicrobial resistance in Neisseria gonorrhoeae in the 21st century: past, evolution, and future. Clin. Microbiol. Rev. 27 (2014), 587–613.
173. Vila, J., Fabrega, A., Roca, I., Hernandez, A., Martinez, J.L., Efflux pumps as an important mechanism for quinolone resistance. Adv. Enzymol. Relat. Areas Mol. Biol. 77 (2011), 167–235.
174. Vila, J., Martínez, J.L., Clinical impact of the over-expression of efflux pump in nonfermentative Gram-negative bacilli, development of efflux pump inhibitors. Curr. Drug Targets 9 (2008), 797–807.
175. Wang, D., Seeve, C., Pierson, L.S., 3rd, E.A., Pierson, Transcriptome profiling reveals links between ParS/ParR, MexEF-OprN, and quorum sensing in the regulation of adaptation and virulence in Pseudomonas aeruginosa. BMC Genomics, 14, 2013, 618.
176. Warner, D.M., Folster, J.P., Shafer, W.M., Jerse, A.E., Regulation of the MtrC-MtrD-MtrE efflux-pump system modulates the in vivo fitness of Neisseria gonorrhoeae. J. Infect. Dis. 196 (2007), 1804–1812.
177. Wassenaar, T.M., Ussery, D., Nielsen, L.N., Ingmer, H., Review and phylogenetic analysis of qac genes that reduce susceptibility to quaternary ammonium compounds in Staphylococcus species. Eur. J. Microbiol. Immunol. 5 (2015), 44–61.
178. Westfall, L.W., Carty, N.L., Layland, N., Kuan, P., Colmer-Hamood, J.A., Hamood, A.N., mvaT mutation modifies the expression of the Pseudomonas aeruginosa multidrug efflux operon mexEF-oprN. FEMS Microbiol. Lett. 255 (2006), 247–254.
179. Wierzbowski, A.K., Boyd, D., Mulvey, M., Hoban, D.J., Zhanel, G.G., Expression of the mef(E) gene encoding the macrolide efflux pump protein increases in Streptococcus pneumoniae with increasing resistance to macrolides. Antimicrob. Agents Chemother. 49 (2005), 4635–4640.
180. Wirsching, S., Moran, G.P., Sullivan, D.J., Coleman, D.C., Morschhauser, J., MDR1-mediated drug resistance in Candida dubliniensis. Antimicrob. Agents Chemother. 45 (2001), 3416–3421.
181. Yamada, Y., Shiota, S., Mizushima, T., Kuroda, T., Tsuchiya, T., Functional gene cloning and characterization of MdeA, a multidrug efflux pump from Staphylococcus aureus. Biol. Pharm. Bull. 29 (2006), 801–804.
182. Yamaguchi, A., Nakashima, R., Sakurai, K., Structural basis of RND-type multidrug exporters. Front. Microbiol., 6, 2015, 327.
183. Yamanaka, H., Kobayashi, H., Takahashi, E., Okamoto, K., MacAB is involved in the secretion of Escherichia coli heat-stable enterotoxin II. J. Bacteriol. 190 (2008), 7693–7698.
184. Yamane, K., Wachino, J., Suzuki, S., Kimura, K., Shibata, N., Kato, H., Shibayama, K., Konda, T., Arakawa, Y., New plasmid-mediated fluoroquinolone efflux pump, QepA, found in an Escherichia coli clinical isolate. Antimicrob. Agents Chemother. 51 (2007), 3354–3360.
185. Ye, H.F., Zhang, M., O'Donoghue, M., Boost, M., Are qacG, qacH and qacJ genes transferring from food isolates to carriage isolates of staphylococci?. J. Hosp. Infect. 80 (2012), 95–96.
186. Yerushalmi, H., Schuldiner, S., A common binding site for substrates and protons in EmrE, an ion-coupled multidrug transporter. FEBS Lett. 476 (2000), 93–97.
187. Yim, G., Wang, H.H., Davies, J., The truth about antibiotics. Int. J. Med. Microbiol. 296 (2006), 163–170.
188. Yoon, E.J., Chabane, Y.N., Goussard, S., Snesrud, E., Courvalin, P., De, E., Grillot-Courvalin, C., Contribution of resistance-nodulation-cell division efflux systems to antibiotic resistance and biofilm formation in Acinetobacter baumannii. MBio, 6, 2015.
189. Yuan, J., Xu, X., Guo, Q., Zhao, X., Ye, X., Guo, Y., Wang, M., Prevalence of the oqxAB gene complex in Klebsiella pneumoniae and Escherichia coli clinical isolates. J. Antimicrob. Chemother. 67 (2012), 1655–1659.
190. Zhang, L., Li, X.Z., Poole, K., SmeDEF multidrug efflux pump contributes to intrinsic multidrug resistance in Stenotrophomonas maltophilia. Antimicrob. Agents Chemother. 45 (2001), 3497–3503.
191. Zhou, J., Zhang, M., Yang, W., Fang, Y., Wang, G., Hou, F., A seventeen-year observation of the antimicrobial susceptibility of clinical Campylobacter jejuni and the molecular mechanisms of erythromycin-resistant isolates in Beijing, China. Int. J. Infect. Dis. 42 (2016), 28–33.
192. Ziha-Zarifi, I., Llanes, C., Kohler, T., Pechere, J.C., Plesiat, P., In vivo emergence of multidrug-resistant mutants of Pseudomonas aeruginosa overexpressing the active efflux system MexA-MexB-OprM. Antimicrob. Agents Chemother. 43 (1999), 287–291.
193. Zughaier, S.M., Kandler, J.L., Shafer, W.M., Neisseria gonorrhoeae modulates iron-limiting innate immune defenses in macrophages. PLOS ONE, 9, 2014, e87688.