Practice question

Efflux-mediated resistance represents highly efficient active extrusion mechanism driven by transmembrane energy gradients. Bacterial multidrug efflux systems belong to five major families: resistance-nodulation-division RND such as AcrAB-TolC tripartite pump in Escherichia coli and MexAB-OprM in Pseudomonas aeruginosa, major facilitator superfamily MFS such as TetA for tetracycline, multidrug and toxic compound extrusion MATE, small multidrug resistance SMR and ATP-binding cassette ABC transporters using ATP hydrolysis rather than proton motive force. These pumps capture antibiotics from periplasmic space or cytoplasmic leaflet and use proton antiport or ATP hydrolysis to export them to extracellular medium, continuously lowering intracellular concentration below inhibitory threshold required for target binding. Overexpression via mutations in local repressors like marR, acrR, mexR or activation of global stress regulators marA, soxS, ramA increases pump copy number and broadens substrate range, conferring cross-resistance to dyes, detergents, bile salts and chemically unrelated antibiotic classes. Unlike enzymatic inactivation that destroys drug chemically, or target site modification via methylation or point mutation that reduces binding affinity, or plasmid transfer that describes gene movement mechanism, efflux physically pumps drug out, exemplifying intrinsic and acquired multidrug resistance especially prominent in Gram-negative pathogens and biofilm-associated tolerant states.