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Chapter 20 : Role of Multidrug Efflux Pumps in Gram-Positive Bacteria

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Role of Multidrug Efflux Pumps in Gram-Positive Bacteria, Page 1 of 2

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Abstract:

Drug efflux pumps possessed by gram-positive organisms are encoded either by plasmid- or chromosomally-based genes. Generally, drug-specific efflux pumps tend to be located on plasmids and thus are readily transmissible, whereas multidrug (MDR) efflux pumps are usually encoded on the chromosome and are not easily donated to another organism. This chapter focuses the discussion entirely on MDR-type pumps. The available genome sequence data for gram-positive organisms suggests the existence of numerous potential drug pumps in all of them. The greatest amount of information regarding the mechanism(s) of pump function and multidrug recognition as well as the regulation of pump gene expression in gram-positive organisms is available for major facilitator superfamily (MFS) MDR efflux pumps. The study of the mechanism of multidrug recognition and transport is hampered by our general inability to produce high-resolution crystals of MDR pump proteins. Further research on bacterial MDR efflux pumps is warranted in an effort to improve our understanding of how these systems work, because such an understanding may allow the development of means to overcome this resistance mechanism and to recover useful activity of their antibiotic substrates.

Citation: Kaatz G. 2005. Role of Multidrug Efflux Pumps in Gram-Positive Bacteria, p 275-286. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch20

Key Concept Ranking

Small Multidrug Resistance Family
0.62517196
Major Facilitator Superfamily
0.48785093
Secondary Active Transporters
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0.62517196
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Figures

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Figure 1

Schematic representation of the general structural characteristics of each family of MDR efflux proteins. ABC, ATP-binding cassette; MFS, major facilitator superfamily; MATE, multidrug and toxin extrusion; SMR, small multidrug resistance; RND, resistance-nodulation-division. The large central loop that is characteristic of MFS proteins is not necessarily as large as that depicted for MATE proteins. The cytoplasmic membrane (CM) is depicted in gray, and the interior and exterior of the cell are as indicated.

Citation: Kaatz G. 2005. Role of Multidrug Efflux Pumps in Gram-Positive Bacteria, p 275-286. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch20
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Image of Figure 2
Figure 2

Regulation of and expression. (A) . A BmrR dimer binds to a ligand, most likely a Bmr substrate, and in turn binds to the promoter activating transcription. The ligand(s) for Mta are currently unknown. (B) . In the absence of a ligand, most likely a QacA substrate, QacR binds as a pair of dimers to the promoter and blocks transcription. Binding of a ligand to each QacR dimer results in a release of its repression on , allowing transcription to proceed.

Citation: Kaatz G. 2005. Role of Multidrug Efflux Pumps in Gram-Positive Bacteria, p 275-286. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch20
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Tables

Generic image for table
Table 1

Drug transport proteins predicted from analysis of genome data

Citation: Kaatz G. 2005. Role of Multidrug Efflux Pumps in Gram-Positive Bacteria, p 275-286. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch20

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