Expression of the <italic>TetA</italic> gene encoding TetA efflux protein in <italic>E. coli</italic> contributes to its increased bacterial resistance toward berberine.

Berberine (BBR) is a traditional Chinese medicine in various applications due to its antibacterial effect. Here we investigated the increased bacterial resistance of <italic>E. coli</italic> toward BBR. The median effective concentration (EC50) of BBR against <italic>E. coli</italic> was increased when TetA efflux protein (TEP) was introduced. Sixty-five percent of the intracellular BBR was expelled and molecular docking demonstrated the intensive interaction of TEP to BBR. Finally, the combined antibacterial experiment identified that BBR acted as an inhibitor of TEP in detoxification of tetracycline. TEP is the first discovered protein that was related to the bacterial susceptibility to BBR. [ABSTRACT FROM AUTHOR]