Abstract
Bacteria have developed various ways to resist the toxic effects of antibiotics and other drugs [1]. One of these mechanisms involves the production of enzymes that inactivate antibiotics by hydrolysis or lead to the formation of inactive derivatives [2]. A second mechanism of resistance is target alteration. Cellular targets can be altered by mutation or enzymatic modification in such a way that the affinity of the antibiotic for the target is reduced [3]. These mechanisms are all specific for a single drug or a single class of drugs. However, there are more general mechanisms of resistance in which access of the unaltered agent to the target is prevented by the barrier and active transport functions of biological membranes. The barrier cannot prevent the drugs from exerting their toxic action once they have entered the cell, and the active efflux of drugs is essential to ensure significant levels of drug resistance [4].
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Neu HC (1992) The crisis in antibiotic resistance. Science 257:1064–1073
Davies J (1994) Inactivation of antibiotics and the dissemination of resistance genes. Science 264:375–382
Spratt BG (1994) Resistance to antibiotics mediated by target alterations. Science 264:388–393
Nikaido H (1994) Prevention of drug access to bacterial targets: permeability barriers and active efflux. Science 264:382–388
Nishino K (2005) Bacterial multidrug exporters: insights into acquisition of multidrug resistance. Science [online publication] http://www.sciencemag.org/feature/data/prizes/ge/2004/nishino.dtl
Nishino K, Latifi T, Groisman EA (2006) Virulence and drug resistance roles of multidrug efflux systems of Salmonella entericaserovar Typhimurium. Mol Microbiol 59:126–141
Nishino K, Yamaguchi A (2008) Role of xenobiotic transporters in bacterial drug resistance and virulence. IUBMB Life 60:569–574
Nishino K, Yamaguchi A (2008) Virulence and drug resistance roles of multidrug efflux pumps in Escherichia coliand Salmonella. Biosci Microflora 27:75–85
Nishino K, Nikaido E, Yamaguchi A (2009) Regulation and physiological function of multidrug efflux pumps in Escherichia coliand Salmonella. Biochim Biophys Acta 1794:834–843
Nishino K, Yamaguchi A (2001) Analysis of a complete library of putative drug transporter genes in Escherichia coli. J Bacteriol 183:5803–5812
Blattner FR, Plunkett G 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y (1997) The complete genome sequence of Escherichia coliK-12. Science 277:1453–1474
Kobayashi N, Nishino K, Yamaguchi A (2001) Novel macrolide-specific ABC-type efflux transporter in Escherichia coli. J Bacteriol 183:5639–5644
Kobayashi N, Nishino K, Hirata T, Yamaguchi A (2003) Membrane topology of ABC-type macrolide antibiotic exporter MacB in Escherichia coli. FEBS Lett 546:241–246
Hirata T, Saito A, Nishino K, Tamura N, Yamaguchi A (2004) Effects of efflux transporter genes on susceptibility of Escherichia colito tigecycline (GAR-936). Antimicrob Agents Chemother 48:2179–2184
Horiyama T, Nikaido E, Yamaguchi A, Nishino K (2011) Roles of Salmonellamultidrug efflux pumps in tigecycline resistance. J Antimicrob Chemother 66:105–110
Cloeckaert A, Chaslus-Dancla E (2001) Mechanisms of quinolone resistance in Salmonella. Vet Res 32:291–300
Baucheron S, Imberechts H, Chaslus-Dancla E, Cloeckaert A (2002) The AcrB multidrug transporter plays a major role in high-level fluoroquinolone resistance in Salmonella entericaserovar typhimurium phage type DT204. Microb Drug Resist 8:281–289
Baucheron S, Chaslus-Dancla E, Cloeckaert A (2004) Role of TolC and parCmutation in high-level fluoroquinolone resistance in Salmonella entericaserotype Typhimurium DT204. J Antimicrob Chemother 53:657–659
Horiyama T, Yamaguchi A, Nishino K (2010) TolC dependency of multidrug efflux systems in Salmonella entericaserovar Typhimurium. J Antimicrob Chemother 65:1372–1376
Hirakawa H, Takumi-Kobayashi A, Theisen U, Hirata T, Nishino K, Yamaguchi A (2008) AcrS/EnvR represses expression of the acrABmultidrug efflux genes in Escherichia coli. J Bacteriol 190:6276–6279
Nishino K, Nikaido E, Yamaguchi A (2007) Regulation of multidrug efflux systems involved in multidrug and metal resistance of Salmonella entericaserovar Typhimurium. J Bacteriol 189:9066–9075
Nikaido E, Yamaguchi A, Nishino K (2008) AcrAB multidrug efflux pump regulation in Salmonella entericaserovar Typhimurium by RamA in response to environmental signals. J Biol Chem 283:24245–24253
Nikaido E, Shirosaka I, Yamaguchi A, Nishino K (2011) Regulation of the AcrAB multidrug efflux pump in Salmonella entericaserovar Typhimurium in response to indole and paraquat. Microbiology 157:648–655
Acknowledgments
I thank all my colleagues who contributed to the work discussed in this review. This study was supported by the funding program for Next Generation World-Leading Researchers from Cabinet Office, Government of Japan, and the grant-in-aid from the Uehara Memorial Foundation.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer
About this paper
Cite this paper
Nishino, K. (2012). Multidrug Efflux Pumps and Development of Therapeutic Strategies to Control Infectious Diseases. In: Shibasaki, M., Iino, M., Osada, H. (eds) Chembiomolecular Science. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54038-0_27
Download citation
DOI: https://doi.org/10.1007/978-4-431-54038-0_27
Published:
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-54037-3
Online ISBN: 978-4-431-54038-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)