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Molecular docking, gyrase supercoiling assay and acetylation assay were used to clarify the mechanism of action. Results Palmatine effectively restored the activity of ciprofloxacin against qnrS and aac(6'-Ib-cr-positive E. coli strains in a synergistic manner in vitro. In addition, the combined therapy significantly reduced the bacterial burden in a mouse thigh infection model. Molecular docking revealed that palmatine bound at the functional large loop B of QnrS and Trp102Arg and Asp179Tyr in the binding pocket of AAC(6'-Ib-cr. Fur
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