Resistance-nodulation-division efflux

Currently, five different molecular classes of mdr efflux pumps are known [5], While pumps of the the ATP-binding cassette (ABC) transporter superfamily are driven by ATP hydrolysis, the other four superfamilies called resistance-nodulation-division (RND), major facilitator superfamily (MFS), multidrug and toxic compound extrusion (MATE), and small multidrag resistance transporter (SMR) are driven by the proton-motive force across the cytoplasmic membrane. Usually a single pump protein is located within the cytoplasmic membrane. However, the RND-type pumps which are restricted to Gram-negative bacteria consist of two additional components, a periplasmic membrane fusion protein (MFP) which connects the efflux pump to an outer... 

Aminoglycoside efflux is a significant mechanism of aminoglycoside resistance in bacteria of the genera Pseudomonas, Burkholderia, and Stenotrophomonas. There are five classes of transmembrane efflux systems associated with antibiotic resistance however, the resistance nodulation division (RND) family is the predominant class (Table 3.1). ... 

Efflux pumps belonging to the resistance-nodulation-division (RND) family are especially effective in generating resistance and often have a wide substrate specificity. An extreme case is the AcrB pump of E. coli, which pumps out the antibiotics tetracychne, chloramphenicol, 6-lactams, novobiocin, fusidic acid, nalidixic acid and fluoroquinolones, as well as detergents, bile salts, various cationic dyes, disinfectants and even solvents. 

Hearn, E.M., Gray, M.R., and Foght, J.M. (2006) Mutations in the central cavity and periplasmic domain affect efflux activity of the resistance-nodulation-division pump EmhB from Pseudomonas fluorescens cLP6a. Journal of Bacteriology,... 

Excluding the MFS, the three largest superfamilies of secondary transporters include the Resistance/ Nodulation/Division (RND) exporters (exclusively export carriers Tseng et al. 1999 Dehnar et al. 2014), the Drug/Metabolite Transporters (DMT) (both uptake and efflux systems Jack et al. 2001 Yen et al. 2010), and the Multidrug/Oligosaccharide/Polysaccharide (MOP) porters (exclusively efflux pumps Hvorup et al. 2003b). These three superfamilies will be examined sequentially in this section. 

An alternative to most of these mechanisms is the existence of efficient efflux systems, so that toxic concentrations of the drug are not achieved. There are three major families of proton-dependent multidrug efflux systems (1) the major facilitator superfamily, (2) the small multidrug resistance family, and (3) the resistance/nodulation/cell division family (Paulsen et al. 1996). It should be emphasized that several of these systems are involved not with antibiotic efflux but with, for example, acriflavine, chlorhexidine, and crystal violet. An attempt is made only to outline a few salient features of the resistance/nodulation/cell division family that mediates antibiotic efflux, and these are given in Table 3.3 (Nikaido 1996). They consist of a transporter, a linker, and an outer membrane channel. 

S. Magnet, P. Courvalin, and T. Lambert, Resistance-nodulation-cell division-type efflux pump involved in aminoglycoside resistance in Acinetobacter baumannii strain BM4454, Antimicrob. Agents Chemother., 45 (2001) 3375-3380. 

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