Tetracycline efflux pump TetA and TetB (TetA/TetB)

TetA and TetB are membrane-bound efflux proteins belonging to the Major Facilitator Superfamily (MFS) that serve as major determinants of tetracycline resistance in Gram-negative bacteria (UniProt P02977, P02980). These transporters function as antiporters, leveraging the energy stored in the bacterial proton motive force—comprising both the membrane potential and the pH gradient—to drive the export of tetracycline-magnesium complexes out of the cell (Microbiology and Molecular Biology Reviews, 2014). By maintaining low intracellular concentrations of the antibiotic, these pumps prevent the drug from binding to its primary target, the 30S ribosomal subunit, thereby neutralizing its bacteriostatic effect (Clinical Microbiology Reviews, 2001). The genes encoding TetA and TetB are frequently located on mobile genetic elements such as plasmids and transposons, facilitating their rapid spread across bacterial populations (Journal of Antibiotics, 1990). Clinically, these pumps are significant because they render first- and second-generation tetracyclines ineffective against many pathogens. Consequently, they are the focus of drug development efforts aimed at creating efflux-evading antibiotics like tigecycline or identifying efflux pump inhibitors (EPIs) that can restore the potency of existing tetracyclines (Nature Reviews Microbiology, 2009).

Other names

Tet(A)Tet(B)Tetracycline resistance proteinClass A tetracycline resistance determinantClass B tetracycline resistance determinantMFS-type tetracycline efflux pump

These pumps function as proton-dependent antiporters that utilize the bacterial proton motive force, specifically the membrane potential and pH gradient, to catalyze the active efflux of tetracycline-divalent cation complexes (e.g., [Mg-tetracycline]+) from the cytoplasm to the extracellular environment (Microbiology and Molecular Biology Reviews, 2014; Journal of Antibiotics, 1990).