Multidrug Resistance in Bacteria, Nikaido 2009 copy

Multidrug Resistance in Bacteria, Nikaido 2009 copy -...

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Multidrug Resistance in Bacteria Hiroshi Nikaido Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3202; email: nhiroshi@berkeley.edu Annu. Rev. Biochem. 2009. 78:119–46 First published online as a Review in Advance on February 20, 2009 The Annual Review of Biochemistry is online at biochem.annualreviews.org This article’s doi: 10.1146/annurev.biochem.78.082907.145923 Copyright c ° 2009 by Annual Reviews. All rights reserved 0066-4154/09/0707-0119$20.00 Key Words R plasmids, transposons, integrons, type IV secretion system, multidrug efflux pumps Abstract Large amounts of antibiotics used for human therapy, as well as for farm animals and even for ±sh in aquaculture, resulted in the selection of pathogenic bacteria resistant to multiple drugs. Multidrug resistance in bacteria may be generated by one of two mechanisms. First, these bacteria may accumulate multiple genes, each coding for resistance to a single drug, within a single cell. This accumulation occurs typically on resistance (R) plasmids. Second, multidrug resistance may also oc- cur by the increased expression of genes that code for multidrug efflux pumps, extruding a wide range of drugs. This review discusses our cur- rent knowledge on the molecular mechanisms involved in both types of resistance. 119 Annu. Rev. Biochem. 2009.78:119-146. Downloaded from arjournals.annualreviews.org by University of Colorado - Boulder on 11/29/09. For personal use only.
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Contents INTRODUCTION. ................. 120 BIOCHEMICAL MECHANISMS OF RESISTANCE. ............... 121 Mutational Alteration of the Target Protein. ........... Enzymatic Inactivation of the Drug. .................... Acquisition of Genes for Less Susceptible Target Proteins from Other Species. ............ 123 Bypassing of the Target. Preventing Drug Access to Targets. . 123 SOURCES OF THE RESISTANCE GENES. .......................... 124 Producing Organisms. ............. Microorganisms in the Environment, Especially Soil. ... 124 ASSEMBLY, MAINTENANCE, AND TRANSFER OF RESISTANCE GENES. .......... Assembly of Resistance Genes in R Plasmids. .................. 125 Maintenance of R Plasmids in the Host Cells. 126 Cell-to-Cell Transfer of R Plasmids. MULTIDRUG EFFLUX PUMPS. ... 128 Multidrug Efflux Pumps Belonging to the Major Facilitator Superfamily. ................... 128 Multidrug Efflux Pumps of the Small Multidrug Resistance Family. ........................ 129 Multidrug Efflux Pumps of Resistance-Nodulation-Division 130 Other Multidrug Efflux Pumps Energized by Ionic Gradients. ... 137 Multidrug Efflux Pumps of the ATP-Binding Cassette 137 MULTIDRUG RESISTANCE CAUSED BY ALTERED PHYSIOLOGICAL STATES. ..... 138 MRSA: methicillin- resistant Staphylococcus aureus Aminoglycosides: bactericidal antibiotics that are active against those gram-negative bacteria, resisting most other antibiotics owing to their low permeability outer membrane INTRODUCTION The discovery of penicillin in 1928 was fol- lowed by the discovery and commercial pro- duction of many other antibiotics. We now take for granted that any infectious disease is curable by antibiotic therapy. Antibiotics are manufac- tured at an estimated scale of about 100,000 tons annually worldwide, and their use had a profound impact on the life of bacteria on earth.
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