Efflux Pumps Case Study
Efflux pumps are transport proteins involved in the extrusion of toxic substrates (including antibiotics) from within cells to the external environment. Multi-drug efflux pumps are known to mediate antibiotic efflux and contribute to antibiotic resistance. There are generally five (5) classes of bacterial efflux pumps namely; (i) the major facilitator superfamily (MFS) transporter, (ii) the ATP-binding cassette (ABC) superfamily, (iii) the resistance-nodulation-division (RND) superfamily, (iv) the small multidrug resistance (SMR), and (v) the multidrug and toxic compound extrusion (MATE) family transporters (14).
The RND superfamily pumps are only found in Gram-negative bacteria while the other four family pumps are widely distributed in both Gram-positive and Gram-negative bacteria. While the primary active transporters of the ABC superfamily utilize ATP hydrolysis for energy, the RND family (and the other superfamilies) derive their required energy for by proton motive force. It is this energy that is used in the extrusion of compounds (15).
2.1 Efflux pumps in P. aeruginosa (MexAB-OprM efflux system)
The RND efflux pumps are most commonly found in Gram negative bacteria like P. aeruginosa. There are several
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aeruginosa multidrug efflux system to be described. It is a pump system that extrudes β-lactams, fluoroquinolones, tetracycline, novobiocin, chloramphenicol, macrolides, sulfonamides and trimethoprim. The MexAB-OprM efflux system confers an intrinsic resistance in P. aeruginosa. The hyper expression of the MexAB-OprM system accounts for the elevated MDR of nalB mutants. Expression of the Mex systems of P. aeruginosa is greatest when the bacteria are stressed such as in osmotic shock or growth in a nutrient-poor medium. Unregulated over-expression of efflux pumps is a great disadvantage to the micro-organism as toxic substrates could be exported and there could be loss of nutrients and metabolic
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