Efflux Gram-negative

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... 

The combined intrinsic activities of different efflux pumps play a major role for the intrinsic resistance of Gram-negative bacteria to macrolides and oxazolidi-nones as well as to the intrinsic resistance of Pseudomonas aeruginosa against a broad range of disinfectants and antibiotics. 

Fig. 9.1 Schematic representation of possible mechanisms of resistance in Gram-negative and Gram-positive bacteria. 1, antibiotic-inactivating enzymes 2, antibiotic efflux proteins 3, alteration or duplication of intracellular targets 4, alteration of the cell membrane reducing antibiotic uptake 5, alterations in porins or lipopolysaccharide reducing antibiotic uptake or binding.

Nikaido H (1996) Multidrug efflux pumps in Gram-negative bacteria. J Bacteriol 178 5853-5859. 

Figure 8.6 Pathways for uptake and efflux of Zn2+ in Gram-negative bacteria. (From Hantke, 2001. With kind permission of Springer Science and Business Media.)...

The RND family of efflux pumps are restricted to gram-negative organisms and consists of three major components the RND pump, a periplasmic membrane fusion protein (MFP), and an outer-membrane factor (OMF). Together these three proteins are able to effectively pump a variety of antibiotics, dyes, and ions depending on the type of RND pump associated with the system (Figure 3.2). The... 

Finally, some gram-negative organisms demonstrate a fourth mechanism of resistance. For example, strains of P. aeruginosa produce xenobiotic efflux pumps to eject antibiotics. Drug efflux mechanisms are associated with multiple drug resistance, including resistance to (3-lactam antibiotics. 

H Nikaido. Antibiotic resistance caused by gram-negative multidrug efflux pumps. Clin Infect Dis 27 Suppl 1 32 11, 1998. 

Gram-negative bacteria, such as E. coli and Pseudomonas, are bound by two membranes, so the efflux pumps must traverse both in order to pump substances out (Figure 20.7). 

---