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Chapter 19 : Role, Structure, and Function of Multidrug Efflux Pumps in Gram-Negative Bacteria

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Role, Structure, and Function of Multidrug Efflux Pumps in Gram-Negative Bacteria, Page 1 of 2

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Abstract:

Genomes of gram-negative bacteria usually contain multiple copies of genes belonging to each of the families of multidrug transporters, such as SMR (small multidrug resistance), MFS (major facilitator superfamily), MATE (multidrug and toxic compound extrusion), and RND (resistance nodulation division). Due to the predominant role RND pumps play in the resistance (both intrinsic and acquired) to commonly used antibiotics, this chapter discusses the pumps of this type in detail; however, the discussion is limited to and , as representative organisms. For soil and water dwellers, it is difficult to pinpoint the “natural” substrate for their main efflux pumps. However, gram-negative bacteria have always faced toxic chemicals in the environment, and outer membrane (OM) cannot completely shut out lipophilic compounds, which can diffuse, albeit slowly, across the asymmetric bilayer of OM. Living in a natural habitat surrounded by high concentrations of bile salts and other antimicrobial inhibitors such as fatty acids, cells are armed with the OM as well as a wide range of efflux pumps. In , , which is divergently transcribed from the genes, encodes a repressor. Perhaps because the inactivation of AcrR results in a too high level of production of AcrAB, it seems to serve only a subsidiary role in the regulation of AcrAB expression.

Citation: Nikaido H. 2005. Role, Structure, and Function of Multidrug Efflux Pumps in Gram-Negative Bacteria, p 261-274. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch19

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Major Facilitator Superfamily
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Integral Membrane Proteins
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Figures

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Figure 1

RND pump complex is likely to capture its amphiphilic substrates from the outer leaflet of IM.

Citation: Nikaido H. 2005. Role, Structure, and Function of Multidrug Efflux Pumps in Gram-Negative Bacteria, p 261-274. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch19
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Image of Figure 2
Figure 2

Three-dimensional structure of the AcrB trimer with liganded ciprofloxacin molecules. This structure shows the N109A mutant AcrB trimer, with six molecules of bound ciprofloxacin (Yu, McDermott, and Nikaido, submitted for publication). The three protomers of AcrB are shown as ribbon diagrams in different shades of gray. The ciprofloxacin molecules are shown in ball-and-stick models, those in the central cavity in light gray, and those in the periplasmic site in black. The drawing was made with DS Viewer Pro (Accelrys, San Diego, Calif.).

Citation: Nikaido H. 2005. Role, Structure, and Function of Multidrug Efflux Pumps in Gram-Negative Bacteria, p 261-274. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch19
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Image of Figure 3
Figure 3

Hypothetical pathway for the lateral capture of substrates by RND group transporters. Cationic dyes and aminoglycosides become adsorbed at the interface region and on the surface of the outer leaflet of IM. Ciprofloxacin is partitioned into IM, with the protonated piperazine amino group near the interface. These substrates diffuse laterally through vestibules into the central cavity, where they become bound to its wall.

Citation: Nikaido H. 2005. Role, Structure, and Function of Multidrug Efflux Pumps in Gram-Negative Bacteria, p 261-274. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch19
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