Chenodeoxycholic Acid-Amikacin Combination Enhances Eradication of Staphylococcus aureus
Kaiyu Cui, Weifeng Yang, Zhiyuan Liu, Guijian Liu, Dongying Li, Yanan Sun, Gaiying He, Shuhua Ma, Yu Cao, Xuefan Jiang, Sylvie Chevalier, Pierre Cornélis, Qing Wei, Yi Wang
Abstract
Multidrug resistance (MDR) is spreading globally with increasing speed. The search for new antibiotics is one of the key strategies in the fight against MDR. Antibiotic resistance breakers that may or may not have direct antibacterial action and can either be coadministered or conjugated with other antibiotics are being studied. To better expand the antibacterial spectrum of certain antibiotics, we identified one component from a traditional Chinese medicine, Tanreqing (TRQ), that increased the activity of aminoglycosides. We found that this so-called agent, chenodeoxycholic acid (CDCA), sensitizes Staphylococcus aureus to aminoglycoside killing and protects a mouse model from S. aureus infections. CDCA increases the uptake of aminoglycosides in a proton motive force-dependent manner by dissipating the chemical potential and potentiates ROS generation by inhibiting superoxide dismutase activity in S. aureus. Our work highlights the potential use of TCM or its effective components, such as CDCA, in treating antibiotic resistance-associated infections.