title: A tanshinone I derivative enhances the activities of antibiotics against Staphylococcus aureus in vitro and in vivo.
abstract: 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 β-lactam 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.
authors.affiliation: Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Science, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Science, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Chunbo
authors.initials: C
authors.lastname: Lu
authors.affiliation: Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Science, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Sun
authors.affiliation: Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Science, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Mingxu
authors.initials: M
authors.lastname: Cui
authors.affiliation: Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Science, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Mu
authors.affiliation: Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Science, Northwest A&F University, Yangling 712100, Shaanxi, China. Electronic address: jduan@nwsuaf.edu.cn.
authors.forename: Jinyou
authors.initials: J
authors.lastname: Duan
authors.affiliation: Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Science, Northwest A&F University, Yangling 712100, Shaanxi, China. Electronic address: genghuiling@nwsuaf.edu.cn.
authors.forename: Huiling
authors.initials: H
authors.lastname: Geng
mesh_terms: D045784:Abietanes / Q000138:chemical synthesis / Q000494:pharmacology*; D000617:Aminoglycosides / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D004347:Drug Interactions; D008657:Metabolic Clearance Rate; D051379:Mice; D013211:Staphylococcus aureus / Q000187:drug effects*; D047090:beta-Lactams / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D045784:Abietanes; D000617:Aminoglycosides; D000890:Anti-Infective Agents; D047090:beta-Lactams; C021751:tanshinone
keywords: Ampicillin; Antibiotic; Combination; Staphylococcus aureus; Streptomycin; Tanshinone I