Tetracycline efflux protein Tet(A) and Tet(B) (TetA/TetB)

TetA and TetB are integral membrane proteins belonging to the Major Facilitator Superfamily (MFS) that serve as primary mediators of tetracycline resistance in Gram-negative bacteria (UniProt P02980, P02981). These pumps function as metal-tetracycline/H+ antiporters, actively extruding tetracycline-metal complexes from the cell using the energy derived from the proton-motive force (Grossman, 2016; PMC4811540). The expression of these pumps is tightly controlled by the TetR repressor protein, which ensures that the energy-intensive pumps are only produced when the antibiotic is present in the environment (Hillen & Berens, 1994; PMID 7942675). TetA and TetB are frequently encoded on mobile genetic elements like plasmids and transposons (e.g., Tn10 for TetB), facilitating their rapid spread among clinical pathogens such as Escherichia coli and Acinetobacter baumannii (CARD ARO:3000166). While they effectively confer resistance to first- and second-generation tetracyclines like doxycycline, newer agents such as tigecycline and eravacycline have been engineered to bypass these efflux mechanisms (Grossman, 2016). Consequently, these pumps are significant targets for the development of efflux pump inhibitors (EPIs) intended to restore the efficacy of traditional tetracycline therapies (MDPI, 2023; PMC10385855).

Other names

Tet(A)Tet(B)Tetracycline resistance protein class ATetracycline resistance protein class BMetal-tetracycline/H+ antiporterTetracycline efflux pumptetA/tetB resistance machinery

The TetA and TetB pumps function as energy-dependent efflux systems that export tetracycline-divalent metal complexes (e.g., [Mg-tetracycline]+) from the bacterial cytoplasm in exchange for a proton (H+), utilizing the proton-motive force (Grossman, 2016; PMC4811540). This process is regulated by the TetR repressor, which binds to the operator region in the absence of the drug; upon binding tetracycline, TetR undergoes a conformational change and dissociates, allowing the transcription of the efflux pump genes (Hillen & Berens, 1994; PMID 7942675).