Multidrug efflux pumps in Gram-negative bacteria and their role in antibiotic resistance.
Abstract
Gram-negative bacteria express a plethora of efflux pumps that are capable of transporting structurally varied molecules, including antibiotics, out of the bacterial cell. This efflux lowers the intracellular antibiotic concentration, allowing bacteria to survive at higher antibiotic concentrations. Overexpression of some efflux pumps can cause clinically relevant levels of antibiotic resistance in Gram-negative pathogens. This review discusses the role of efflux in resistance of clinical isolates of Gram-negative bacteria, the regulatory mechanisms that control efflux pump expression, the recent advances in our understanding of efflux pump structure and how inhibition of efflux is a promising future strategy for tackling multidrug resistance in Gram-negative pathogens.
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The efflux pump system is present in almost all species and plays important roles in drug resistance in bacteria, fungi and human cancer cells by efflux of the drugs.
“The efflux pump system, which is comprised of pumps located in the cell membrane and their regulators, is present in almost all species and plays an important roles in drug resistance in bacteria, fungi and human cancer cells by efflux of the drugs (Golin et al., 2007; Blair et al., 2014; Cowen et al., 2014; Paul and Moye-Rowley, 2014; Tanwar et al., 2014; Kathawala et al., 2015).”
From Abnormal Ergosterol Biosynthesis Activates Transcriptional Responses to Antifungal Azoles (2018) · cites this paper as Blair et al., 2014
Cites
Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen
Stover, C. K., Pham, X. Q., Erwin, A. L., Mizoguchi, S., Warrener, P., Hickey, M. J., Brinkman, F. S. L., HUFNAGLE, W. O., Kowalik, D., Mj, L., et al. (2000) · Nature · doi:10.1038/35023079 · Cited by 4,544 · see citing works
Two-Component Signal Transduction
Stock, A., Robinson, V. L., & Goudreau, P. N. (2000) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.69.1.183 · Cited by 3,653 · see citing works
Multidrug-resistance efflux pumps ? not just for resistance
Piddock, L. J. V. (2006) · Nature Reviews Microbiology · doi:10.1038/nrmicro1464 · Cited by 1,523 · see citing works
Self-citationClinically Relevant Chromosomally Encoded Multidrug Resistance Efflux Pumps in Bacteria
Piddock, L. J. V. (2006) · Clinical Microbiology Reviews · doi:10.1128/cmr.19.2.382-402.2006 · Cited by 1,231 · see citing works
Self-citationGlobal Challenge of Multidrug-Resistant Acinetobacter baumannii
Pérez, F., Hujer, A. M., Hujer, K. M., Decker, B. K., Rather, P. N., & Bonomo, R. A. (2007) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01464-06 · Cited by 1,138 · see citing works
Histidine kinases and response regulator proteins in two-component signaling systems
West, A. H., & Stock, A. (2001) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(01)01852-7 · Cited by 956 · see citing works
The importance of efflux pumps in bacterial antibiotic resistance
Webber, M. A. (2002) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkg050 · Cited by 856 · see citing works
Okusu, H., Ma, D., & Nikaido, H. (1996) · Journal of Bacteriology · doi:10.1128/jb.178.1.306-308.1996 · Cited by 818 · see citing works
Flexibility in the ABC transporter MsbA: Alternating access with a twist
Ward, A. B., Reyes, C. L., Yu, J., Roth, C., & Chang, G. A. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709388104 · Cited by 774 · see citing works
Crystal structures of a multidrug transporter reveal a functionally rotating mechanism
Murakami, S., Nakashima, R., Yamashita, E., Matsumoto, T., & Yamaguchi, A. (2006) · Nature · doi:10.1038/nature05076 · Cited by 772 · see citing works
Intrinsic antibiotic resistance: Mechanisms, origins, challenges and solutions
Cox, G., & Wright, G. D. (2013) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2013.02.009 · Cited by 721 · see citing works
Masuda, N., Sakagawa, E., Ohya, S., Gotoh, N., Tsujimoto, H., & Nishino, T. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.12.3322-3327.2000 · Cited by 720 · see citing works
Structure of the AcrAB–TolC multidrug efflux pump
Du, D., Wang, Z., James, N. R., Voss, J. E., Klimont, E., Ohene‐Agyei, T., Venter, H., Chiu, W., & Luisi, B. F. (2014) · Nature · doi:10.1038/nature13205 · Cited by 664 · see citing works
Magnet, S., Courvalin, P. M., & Lambert, T. (2001) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.45.12.3375-3380.2001 · Cited by 574 · see citing works
CmeABC Functions as a Multidrug Efflux System in Campylobacter jejuni
Lin, J., Michel, L. O., & Zhang, Q. (2002) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.46.7.2124-2131.2002 · Cited by 529 · see citing works
Efflux-Mediated Antibiotic Resistance in Acinetobacter spp
Coyne, S., Courvalin, P. M., & Périchon, B. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01388-10 · Cited by 519 · see citing works
Pomposiello, P. J., Bennik, M. H. J., & Demple, B. (2001) · Journal of Bacteriology · doi:10.1128/jb.183.13.3890-3902.2001 · Cited by 487 · see citing works
Regulation of chromosomally mediated multiple antibiotic resistance: the mar regulon
Alekshun, M. N., & Levy, S. B. (1997) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.41.10.2067 · Cited by 476 · see citing works
Molecular cloning and characterization of acrA and acrE genes of Escherichia coli
Ma, D., Cook, D. N., Alberti, M., Pon, N. G., Nikaido, H., & Hearst, J. E. (1993) · Journal of Bacteriology · doi:10.1128/jb.175.19.6299-6313.1993 · Cited by 466 · see citing works
Lomovskaya, O., & Bostian, K. A. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2005.12.008 · Cited by 461 · see citing works
Emr, an Escherichia coli locus for multidrug resistance.
Lomovskaya, O., & Lewis, K. (1992) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.89.19.8938 · Cited by 444 · see citing works
Signal integration in bacterial two-component regulatory systemsPreprint
Mitrophanov, A. Y., & Groisman, E. A. (2008) · Genes & Development · doi:10.1101/gad.1700308 · Cited by 415 · see citing works
Marchand, I., Damier-Piolle, L., Courvalin, P. M., & Lambert, T. (2004) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.48.9.3298-3304.2004 · Cited by 406 · see citing works
Li, X. Z., Livermore, D. M., & Nikaido, H. (1994) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.38.8.1732 · Cited by 403 · see citing works
Morita, Y., Kodama, K., Shiota, S., Mine, T., Kataoka, A., Mizushima, T., & Tsuchiya, T. (1998) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.42.7.1778 · Cited by 391 · see citing works
Ma, D., Alberti, M., Lynch, C., Nikaido, H., & Hearst, J. E. (1996) · Molecular Microbiology · doi:10.1046/j.1365-2958.1996.357881.x · Cited by 390 · see citing works
Structure of the Multidrug Transporter EmrD from Escherichia coli
Yin, Y., He, X., Szewczyk, P., Nguyen, T., & Chang, G. A. (2006) · Science · doi:10.1126/science.1125629 · Cited by 387 · see citing works
Nishino, K., Latifi, T. N., & Groisman, E. A. (2005) · Molecular Microbiology · doi:10.1111/j.1365-2958.2005.04940.x · Cited by 385 · see citing works
Efflux-Mediated Resistance to Fluoroquinolones in Gram-Negative Bacteria
Poole, K. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.9.2233-2241.2000 · Cited by 372 · see citing works
Inactivation of Efflux Pumps Abolishes Bacterial Biofilm Formation
Kvist, M., Hancock, V., & Klemm, P. (2008) · Applied and Environmental Microbiology · doi:10.1128/aem.01310-08 · Cited by 353 · see citing works
Structures of the multidrug exporter AcrB reveal a proximal multisite drug-binding pocket
Nakashima, R., Sakurai, K., Yamasaki, S., Nishino, K., & Yamaguchi, A. (2011) · Nature · doi:10.1038/nature10641 · Cited by 348 · see citing works
White, D. G., Goldman, J. D., Demple, B., & Levy, S. B. (1997) · Journal of Bacteriology · doi:10.1128/jb.179.19.6122-6126.1997 · Cited by 347 · see citing works
Eicher, T., Cha, H.-J., Seeger, M. A., Brandstätter, L., El-Delik, J., Bohnert, J. A., Kern, W. V., Verrey, F., Grütter, M. G., Diederichs, K., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1114944109 · Cited by 340 · see citing works
Yerushalmi, H. F., Lebendiker, M., & Schuldiner, S. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.12.6856 · Cited by 337 · see citing works
Cohen, S., Levy, S. B., Foulds, J. D., & Rosner, J. L. (1993) · Journal of Bacteriology · doi:10.1128/jb.175.24.7856-7862.1993 · Cited by 330 · see citing works
Indole induces the expression of multidrug exporter genes in Escherichia coli
Hirakawa, H., Inazumi, Y., Masaki, T., Hirata, T., & Yamaguchi, A. (2005) · Molecular Microbiology · doi:10.1111/j.1365-2958.2004.04449.x · Cited by 328 · see citing works
Goodman, A. L., Merighi, M., Hyodo, M., Ventre, I., Filloux, A., & Lory, S. J. (2009) · Genes & Development · doi:10.1101/gad.1739009 · Cited by 325 · see citing works
Preventing drug access to targets: cell surface permeability barriers and active efflux in bacteria
Nikaido, H. (2001) · Seminars in Cell and Developmental Biology · doi:10.1006/scdb.2000.0247 · Cited by 319 · see citing works
Paulsen, I. T., Skurray, R. A., Tam, R., Saier, M. H., Turner, R. J., Weiner, J. H., Goldberg, E. B., & Grinius, L. (1996) · Molecular Microbiology · doi:10.1111/j.1365-2958.1996.tb02462.x · Cited by 317 · see citing works
Evolution of Two-Component Signal Transduction
Koretke, K. K., Lupas, A. N., Warren, P. V., Rosenberg, M. J., & Brown, J. R. (2000) · Molecular Biology and Evolution · doi:10.1093/oxfordjournals.molbev.a026297 · Cited by 315 · see citing works
Structural basis for the inhibition of bacterial multidrug exporters
Nakashima, R., Sakurai, K., Yamasaki, S., Hayashi, K., Nagata, C., Hoshino, K., Onodera, Y., Nishino, K., & Yamaguchi, A. (2013) · Nature · doi:10.1038/nature12300 · Cited by 298 · see citing works
Baranova, N. N., & Nikaido, H. (2002) · Journal of Bacteriology · doi:10.1128/jb.184.15.4168-4176.2002 · Cited by 290 · see citing works
Efflux-Mediated Resistance to Tigecycline (GAR-936) in <i>Pseudomonas aeruginosa</i> PAO1
Dean, C. R., Visalli, M. A., Projan, S. J., Sum, P.-E., & Bradford, P. A. (2003) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.47.3.972-978.2003 · Cited by 286 · see citing works
Li, X. Z., Ma, D., Livermore, D. M., & Nikaido, H. (1994) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.38.8.1742 · Cited by 278 · see citing works
X-ray structure of EmrE supports dual topology model
Chen, Y.-J., Pornillos, O., Lieu, S. S., Ma, C., Chen, A. P., & Chang, G. A. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709387104 · Cited by 278 · see citing works
Llanes, C., Hocquet, D., Vogne, C., Benali-Baitich, D., Neuwirth, C., & Plésiat, P. (2004) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.48.5.1797-1802.2004 · Cited by 278 · see citing works
Structure of a cation-bound multidrug and toxic compound extrusion transporter
He, X., Szewczyk, P., Karyakin, A., Evin, M., Hong, W., Zhang, Q., & Chang, G. A. (2010) · Nature · doi:10.1038/nature09408 · Cited by 272 · see citing works
Evolutionary origins of multidrug and drug-specific efflux pumps in bacteria
Saier, M. H., Paulsen, I. T., Sliwinski, M. K., Pao, S. S., Skurray, R. A., & Nikaido, H. (1998) · The FASEB Journal · doi:10.1096/fasebj.12.3.265 · Cited by 262 · see citing works
Schweizer, H. P. (2012) · Future Microbiology · doi:10.2217/fmb.12.116 · Cited by 258 · see citing works
Tigecycline Efflux as a Mechanism for Nonsusceptibility in Acinetobacter baumannii
Peleg, A. Y., Adams, J. M., & Paterson, D. L. (2007) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01198-06 · Cited by 257 · see citing works
Yoon, E.-J., Courvalin, P. M., & Grillot‐Courvalin, C. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02556-12 · Cited by 257 · see citing works
Multidrug binding properties of the AcrB efflux pump characterized by molecular dynamics simulations
Vargiu, A. V., & Nikaido, H. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1218348109 · Cited by 232 · see citing works
The AcrAB-TolC efflux system of Salmonella enterica serovar Typhimurium plays a role in pathogenesis
Buckley, A. M., Webber, M. A., Cooles, S. W., Randall, L. P., Ragione, R. M. L., Woodward, M. J., & Piddock, L. J. V. (2006) · Cellular Microbiology · doi:10.1111/j.1462-5822.2005.00671.x · Cited by 231 · see citing works
Self-citationCrystal structure of the CusBA heavy-metal efflux complex of Escherichia coli
Su, C., Long, F., Zimmermann, M. T., Rajashankar, K. R., Jernigan, R. L., & Yu, E. W. (2011) · Nature · doi:10.1038/nature09743 · Cited by 228 · see citing works
Nishino, K., Nikaido, E., & Yamaguchi, A. (2007) · Journal of Bacteriology · doi:10.1128/jb.01045-07 · Cited by 223 · see citing works
Multidrug efflux pumps and resistance: regulation and evolution
Paulsen, I. T. (2003) · Current Opinion in Microbiology · doi:10.1016/j.mib.2003.08.005 · Cited by 220 · see citing works
Srinivasan, V. B., & Rajamohan, G. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02284-12 · Cited by 216 · see citing works
Oethinger, M. D., Kern, W. V., Jellen-Ritter, A., McMurry, L. M., & Levy, S. B. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.1.10-13.2000 · Cited by 213 · see citing works
Jerse, A. E., Sharma, N. D., Simms, A. N., Crow, E. T., Snyder, L. A. S., & Shafer, W. M. (2003) · Infection and Immunity · doi:10.1128/iai.71.10.5576-5582.2003 · Cited by 209 · see citing works
Warner, D. M., Shafer, W. M., & Jerse, A. E. (2008) · Molecular Microbiology · doi:10.1111/j.1365-2958.2008.06424.x · Cited by 203 · see citing works
Ruzin, A. V., Visalli, M. A., Keeney, D. R., & Bradford, P. A. (2005) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.49.3.1017-1022.2005 · Cited by 203 · see citing works
Takatsuka, Y., Chen, C., & Nikaido, H. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1001460107 · Cited by 196 · see citing works
Rumbo, C., Gato, E., López, M. C., et al. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00730-13 · Cited by 194 · see citing works
Baucheron, S., Tyler, S. D., Boyd, D. A., Mulvey, M. R., Chaslus-Dancla, E., & Cloeckaert, A. (2004) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.48.10.3729-3735.2004 · Cited by 191 · see citing works
Baugh, S. D. P., Ekanayaka, A. S., Piddock, L. J. V., & Webber, M. A. (2012) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dks228 · Cited by 189 · see citing works
Self-citationSrikumar, R., Kon, T., Gotoh, N., & Poole, K. (1998) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.42.1.65 · Cited by 184 · see citing works
Abouzeed, Y. M., Baucheron, S., & Cloeckaert, A. (2008) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00084-08 · Cited by 173 · see citing works
Eaves, D. J., Ricci, V., & Piddock, L. J. V. (2004) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.48.4.1145-1150.2004 · Cited by 173 · see citing works
Self-citationIdentification and molecular characterisation of CmeB, aCampylobacter jejunimultidrug efflux pump
Pumbwe, L., & Piddock, L. J. V. (2002) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2002.tb11007.x · Cited by 168 · see citing works
Self-citationGriffith, K. L., Shah, I. M., & Wolf, R. E. (2004) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03952.x · Cited by 167 · see citing works
Oethinger, M. D., Podglajen, I., Kern, W. V., & Levy, S. B. (1998) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.42.8.2089 · Cited by 165 · see citing works
Inhibition of multidrug efflux as a strategy to prevent biofilm formation
Baugh, S. D. P., Phillips, C. R., Ekanayaka, A. S., Piddock, L. J. V., & Webber, M. A. (2013) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkt420 · Cited by 158 · see citing works
Self-citationKeeney, D. R., Ruzin, A. V., McAleese, F., Murphy, E., & Bradford, P. A. (2007) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkm397 · Cited by 155 · see citing works
Nishino, K., & Yamaguchi, A. (2002) · Journal of Bacteriology · doi:10.1128/jb.184.8.2319-2323.2002 · Cited by 153 · see citing works
Köhler, T., Kok, M., Michea-Hamzehpour, M., et al. (1996) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.40.10.2288 · Cited by 151 · see citing works
Jellen-Ritter, A., & Kern, W. V. (2001) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.45.5.1467-1472.2001 · Cited by 150 · see citing works
Morita, Y., Sobel, M. L., & Poole, K. (2006) · Journal of Bacteriology · doi:10.1128/jb.188.5.1847-1855.2006 · Cited by 149 · see citing works
SmeC, an Outer Membrane Multidrug Efflux Protein of Stenotrophomonas maltophilia
Li, X.-Z., Zhang, L., & Poole, K. (2002) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.46.2.333-343.2002 · Cited by 147 · see citing works
Srinivasan, V. B., Rajamohan, G., & Gebreyes, W. A. (2009) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00748-09 · Cited by 145 · see citing works
Li, X.-Z., Poole, K., & Nikaido, H. (2002) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.47.1.27-33.2003 · Cited by 144 · see citing works
Akiba, M., Lin, J., Barton, Y.-W., & Zhang, Q. (2005) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dki419 · Cited by 141 · see citing works
Non-Target Gene Mutations in the Development of Fluoroquinolone Resistance in Escherichia coli
Kern, W. V., Oethinger, M. D., Jellen-Ritter, A., & Levy, S. B. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.4.814-820.2000 · Cited by 140 · see citing works
RND Efflux Pumps: Structural Information Translated into Function and Inhibition Mechanisms
Ruggerone, P., Murakami, S., Pos, K. M., & Vargiu, A. V. (2013) · Current Topics in Medicinal Chemistry · doi:10.2174/15680266113136660220 · Cited by 139 · see citing works
Perić, M., Bozdoğan, B., Jacobs, M. R., & Appelbaum, P. C. (2003) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.47.3.1017-1022.2003 · Cited by 138 · see citing works
AdeABC-mediated efflux and tigecycline MICs for epidemic clones of Acinetobacter baumannii
Hornsey, M., Ellington, M. J., Doumith, M., et al. (2010) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkq218 · Cited by 138 · see citing works
Piddock, L. J. V., White, D. G., Gensberg, K., Pumbwe, L., & Griggs, D. J. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.11.3118-3121.2000 · Cited by 137 · see citing works
Self-citationHe, G.-X., Kuroda, T., Mima, T., Morita, Y., Mizushima, T., & Tsuchiya, T. (2003) · Journal of Bacteriology · doi:10.1128/jb.186.1.262-265.2004 · Cited by 136 · see citing works
Chan, Y. Y., & Chua, K. L. (2005) · Journal of Bacteriology · doi:10.1128/jb.187.14.4707-4719.2005 · Cited by 136 · see citing works
Yoshida, K., Nakayama, K., Ohtsuka, M., Kuru, N., Yokomizo, Y., Sakamoto, A., Takemura, M., Hoshino, K., Kanda, H., Nitanai, H., et al. (2007) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2007.07.039 · Cited by 134 · see citing works
Bacterial multidrug transport through the lens of the major facilitator superfamily
Fluman, N., & Bibi, E. (2008) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2008.11.020 · Cited by 131 · see citing works
Transcriptional regulation of drug efflux genes by EvgAS, a two-component system in Escherichia coli
Eguchi, Y., Oshima, T., Mori, H., Aono, R., Yamamoto, K., Ishihama, A., & Utsumi, R. (2003) · Microbiology · doi:10.1099/mic.0.26460-0 · Cited by 130 · see citing works
Ricci, V., Tzakas, P., Buckley, A. M., Coldham, N. G., & Piddock, L. J. V. (2005) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.50.1.38-42.2006 · Cited by 129 · see citing works
Self-citationRole of Histone-Like Protein H-NS in Multidrug Resistance of Escherichia coli
Nishino, K., & Yamaguchi, A. (2004) · Journal of Bacteriology · doi:10.1128/jb.186.5.1423-1429.2004 · Cited by 125 · see citing works
Srikumar, R., Li, X., & Poole, K. (1997) · Journal of Bacteriology · doi:10.1128/jb.179.24.7875-7881.1997 · Cited by 121 · see citing works
Roca, I., Martí, S., Espinal, P., et al. (2009) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00584-09 · Cited by 121 · see citing works
Higgins, P. G., Wisplinghoff, H., Stefanik, D., & Seifert, H. (2004) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkh427 · Cited by 120 · see citing works
Bailey, A. M., Ivens, A. C., Kingsley, R. A., Cottell, J. L., Wain, J. R., & Piddock, L. J. V. (2010) · Journal of Bacteriology · doi:10.1128/jb.01517-09 · Cited by 118 · see citing works
Self-citationHagman, K. E., Lucas, C. E., Balthazar, J. T., et al. (1997) · Microbiology · doi:10.1099/00221287-143-7-2117 · Cited by 117 · see citing works
Miyamae, S., Ueda, O., Yoshimura, F., Hwang, J., Tanaka, Y., & Nikaido, H. (2001) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.45.12.3341-3346.2001 · Cited by 117 · see citing works
The crystal structure of multidrug-resistance regulator RamR with multiple drugs
Yamasaki, S., Nikaido, E., Nakashima, R., et al. (2013) · Nature Communications · doi:10.1038/ncomms3078 · Cited by 116 · see citing works
Nikaido, E., Giraud, É., Baucheron, S., Yamasaki, S., Wiedemann, A., Okamoto, K., Takagi, T., Yamaguchi, A., Cloeckaert, A., & Nishino, K. (2012) · Gut Pathogens · doi:10.1186/1757-4749-4-5 · Cited by 116 · see citing works
Olliver, A., Vallé, M., Chaslus-Dancla, E., & Cloeckaert, A. (2004) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.49.1.289-301.2005 · Cited by 115 · see citing works
nalD Encodes a Second Repressor of the mexAB-oprM Multidrug Efflux Operon of Pseudomonas aeruginosa
Morita, Y., Cao, L., Gould, V. C., et al. (2006) · Journal of Bacteriology · doi:10.1128/jb.01342-06 · Cited by 111 · see citing works
Hornsey, M., Loman, N. J., Wareham, D. W., et al. (2011) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkr168 · Cited by 109 · see citing works
Pontel, L. B., Audero, M. E. P., Espariz, M., Checa, S. K., & Soncini, F. C. (2007) · Molecular Microbiology · doi:10.1111/j.1365-2958.2007.05963.x · Cited by 108 · see citing works
Chollet, R., Chevalier, J., Bryskier, A., & Pagès, J. (2004) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.48.9.3621-3624.2004 · Cited by 108 · see citing works
Blair, J. M. A., Smith, H. E., Ricci, V., Lawler, A. J., Thompson, L. J., & Piddock, L. J. V. (2014) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dku380 · Cited by 102 · see citing works
Self-citationOlliver, A., Vallé, M., Chaslus-Dancla, E., & Cloeckaert, A. (2004) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2004.tb09766.x · Cited by 97 · see citing works
Structure and Operation of Bacterial Tripartite Pumps
Hinchliffe, P., Symmons, M. F., Hughes, C., & Koronakis, V. E. (2013) · Annual Review of Microbiology · doi:10.1146/annurev-micro-092412-155718 · Cited by 90 · see citing works
Sun, J., Perng, C., Chan, M.-C., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0049534 · Cited by 89 · see citing works
Pumbwe, L. (2004) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkh331 · Cited by 88 · see citing works
Newly identified genes involved in the signal transduction of Escherichia coli K-12
Utsumi, R., Katayama, S., Taniguchi, M., et al. (1994) · Gene · doi:10.1016/0378-1119(94)90733-1 · Cited by 80 · see citing works
Efflux pump inhibitors reduce the invasiveness of Pseudomonas aeruginosa
Hirakata, Y., Kondo, A., Hoshino, K., et al. (2009) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2009.06.007 · Cited by 77 · see citing works
Webber, M. A., Talukder, A., & Piddock, L. J. V. (2005) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.49.10.4390-4392.2005 · Cited by 76 · see citing works
Self-citationde Cristóbal, R. E. (2006) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkl172 · Cited by 76 · see citing works
Rouquette, C., Balthazar, J. T., Hill, S. A., & Shafer, W. M. (2004) · Molecular Microbiology · doi:10.1111/j.1365-2958.2004.04299.x · Cited by 74 · see citing works
Nikaido, E., Shirosaka, I., Yamaguchi, A., & Nishino, K. (2010) · Microbiology · doi:10.1099/mic.0.045757-0 · Cited by 73 · see citing works
Hay, T. J. M., Fraud, S., Lau, C. H., Gilmour, C., & Poole, K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0056858 · Cited by 71 · see citing works
AcrS/EnvR Represses Expression of theacrABMultidrug Efflux Genes inEscherichia coli
Hirakawa, H., Takumi-Kobayashi, A., Theisen, U., et al. (2008) · Journal of Bacteriology · doi:10.1128/jb.00190-08 · Cited by 71 · see citing works
Wolter, D. J., Moland, E. S., Goering, R. V., Hanson, N. D., & Lister, P. (2004) · Diagnostic Microbiology and Infectious Disease · doi:10.1016/j.diagmicrobio.2004.05.004 · Cited by 70 · see citing works
Purssell, A., & Poole, K. (2013) · Microbiology · doi:10.1099/mic.0.069286-0 · Cited by 70 · see citing works
The multidrug resistance efflux complex, EmrAB from Escherichia coli forms a dimer in vitro
Tanabe, M., Szakonyi, G., Brown, K. A., et al. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.01.081 · Cited by 69 · see citing works
Transcription ofemrKYis Regulated by the EvgA-EvgS Two-Component System inEscherichia coliK-12
Kato, A., Ohnishi, H., Yamamoto, K., et al. (2000) · Bioscience Biotechnology and Biochemistry · doi:10.1271/bbb.64.1203 · Cited by 69 · see citing works
Protein Modulator of Multidrug Efflux Gene Expression inPseudomonas aeruginosa
Daigle, D. M., Cao, L., Fraud, S., Wilke, M. S., Pacey, A., Klinoski, R., Strynadka, N. C. J., Dean, C. R., & Poole, K. (2007) · Journal of Bacteriology · doi:10.1128/jb.00543-07 · Cited by 68 · see citing works
Bina, X. R., Lavine, C. L., Miller, M. A., & Bina, J. E. (2008) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2007.01033.x · Cited by 63 · see citing works
Huda, M. N., Chen, J., Morita, Y., Kuroda, T., Mizushima, T., & Tsuchiya, T. (2003) · Microbiology and Immunology · doi:10.1111/j.1348-0421.2003.tb03379.x · Cited by 61 · see citing works
RamA, which controls expression of the MDR efflux pump AcrAB-TolC, is regulated by the Lon protease
Ricci, V., Blair, J. M. A., & Piddock, L. J. V. (2013) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkt432 · Cited by 59 · see citing works
Self-citationTwo Efflux Systems Expressed Simultaneously in Multidrug-Resistant Pseudomonas aeruginosa
Pumbwe, L., & Piddock, L. J. V. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.10.2861-2864.2000 · Cited by 58 · see citing works
Self-citationPodnecky, N. L., Wuthiekanun, V., Peacock, S. J., et al. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00660-13 · Cited by 58 · see citing works
Baucheron, S., Coste, F., Canépa, S., et al. (2011) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.05444-11 · Cited by 54 · see citing works
Huang, L., Sun, L., Xu, G., et al. (2008) · Diagnostic Microbiology and Infectious Disease · doi:10.1016/j.diagmicrobio.2008.06.008 · Cited by 54 · see citing works
Xu, X., Xianzhong, S., Morita, Y., Kuroda, T., Mizushima, T., & Tsuchiya, T. (2003) · Microbiology and Immunology · doi:10.1111/j.1348-0421.2003.tb03467.x · Cited by 49 · see citing works
Bacterial Membranes: Structural and Molecular Biology
Remaut, H. K., & Fronzes, R. (2014) · Cited by 48 · see citing works
Hornsey, M., Ellington, M. J., Doumith, M., et al. (2010) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2010.01.011 · Cited by 47 · see citing works
Effect of NlpE Overproduction on Multidrug Resistance in Escherichia coli
Nishino, K., Yamasaki, S., Hayashi-Nishino, M., et al. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01677-09 · Cited by 47 · see citing works
Ricci, V., & Piddock, L. J. V. (2009) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkp054 · Cited by 46 · see citing works
Self-citationCrystal structure of AcrB complexed with linezolid at 3.5 Å resolution
Hung, L., Kim, H.-B., Murakami, S., et al. (2013) · Journal of Structural and Functional Genomics · doi:10.1007/s10969-013-9154-x · Cited by 44 · see citing works
Olliver, A., Valle, M., Chaslus-Dancla, E., et al. (2004) · HAL (Le Centre pour la Communication Scientifique Directe) · Cited by 38 · see citing works
Ricci, V., Busby, S. J. W., & Piddock, L. J. V. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01320-12 · Cited by 33 · see citing works
Self-citationBaucheron, S., Hello, S. L., Doublet, B., et al. (2013) · Frontiers in Microbiology · doi:10.3389/fmicb.2013.00213 · Cited by 29 · see citing works
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Crystal Structures of Membrane Transporter MmpL3, an Anti-TB Drug Target
Zhang, B., Li, J., Yang, X., Wu, L., Zhang, J., Yang, Y., Zhao, Y., Zhang, L., Yang, X., Yang, X., et al. (2019) · Cell · doi:10.1016/j.cell.2019.01.003 · Cited by 263 · see citing works
Abnormal Ergosterol Biosynthesis Activates Transcriptional Responses to Antifungal Azoles
Hu, C., Zhou, M., Wang, W., Sun, X., Yarden, O., & Li, S. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.00009 · Cited by 114 · see citing works
- Authors
- Blair, J. M., Richmond, G. E., & Piddock, L. J.
- Affiliations
- University of Birmingham (GB)
- Venue
- Future Microbiology
- Publisher
- Informa UK Limited
- Published
- 2014-10
- Volume
- 9
- Issue
- 10
- Pages
- 1165-1177
- ISSN
- 1746-0913 (ISSN-L)
- 1746-0921
- OpenAlex
- W2142400495
- Cited by
- 481
- References
- 140
- Citations by year
- 2026: 34 · 2025: 59 · 2024: 62 · 2023: 74 · 2022: 43 · 2021: 38 · 2020: 51 · 2019: 32 · 2018: 26 · 2017: 31 · 2016: 16 · 2015: 15
- FWCI
- 1.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Future Microbiology (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- multidrug efflux pumps, Gram-negative bacteria, antibiotic resistance, efflux pump regulation, efflux pump inhibitors, clinical isolates, multidrug resistance
- MeSH terms
- Anti-Bacterial Agents, Gram-Negative Bacteria, Drug Resistance, Bacterial, Membrane Transport Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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