A tanshinone I derivative enhances the activities of antibiotics against Staphylococcus aureus in vitro and in vivo

Infections caused by Staphylococcus aureus are prevalent. The dramatically reduced discovery of new antibiotics, as well as the persistent emergence of resistant bacteria, represents a major health problem in both hospital and community settings. Using antibiotic enhancers to rescue existing classes of antibiotics is an attractive strategy. In this study, 16-aldehyde tanshinone I (ALT) was synthesized and bacteriostatic activity was explored. In addition, synergistic or additive activity between ALT and aminoglycoside antibiotics or /3-1actam antibiotics in vitro was identified. Moreover, ALT was documented to augment clearance of streptomycin (STR) and ampicillin (AMP) against S. aureus in a murine infection model. Primary mechanistic insight indicated that ALT could damage the bacterial cell membrane, leading to accumulation of antibiotics inside bacterial cells. This finding might be useful for treating infections caused by S. aureus and expand the scope of application of tanshinones. (C) 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.