Antibiotic resistance caused by gram-negative multidrug efflux pumps.
Minimum inhibitory concentrations (MICs) of most lipophilic agents tend to be much higher against gram-negative than gram-positive bacteria. Multidrug efflux pumps that traverse both the inner and outer membranes make a major contribution to this intrinsic resistance of gram-negative bacteria. Such a pump is composed of at least three components, is energized by the proton-motive force, and can pump out not only an extremely wide variety of detergents, dyes, and antibiotics, but also those compounds, such as beta-lactams, that do not easily cross the cytoplasmic membrane. Increased expression of these pumps can raise the MICs to an impressive level. For example, 80% of carbenicillin-resistant clinical isolates of Pseudomonas aeruginosa from the British Isles owed their resistance to overexpression of an efflux pump and had carbenicillin MICs that were up to 2,000 times higher than that of the pump-deficient mutant strain.
Nikaido
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Department of Molecular and Cell Biology, University of California, Berkeley 94720-3206, USA.
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002463:Cell Membrane Permeability; D004352:Drug Resistance, Microbial; D029968:Escherichia coli Proteins; D019143:Evolution, Molecular; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins
D001426:Bacterial Proteins; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; D008074:Lipoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C083497:AcrA protein, E coli; C083496:AcrB protein, E coli