title: Artesunate has its enhancement on antibacterial activity of β-lactams via increasing the antibiotic accumulation within methicillin-resistant Staphylococcus aureus (MRSA).
abstract: Methicillin-resistant Staphylococcus aureus (MRSA) has now emerged as a predominant and serious pathogen because of its resistance to a large group of antibiotics, leading to high morbidity and mortality. Therefore, to develop new agents against resistance is urgently required. Previously, artesunate (AS) was found to enhance the antibacterial effect of β-lactams against MRSA. In this study, AS was first found to increase the accumulation of antibiotics (daunorubicin and oxacillin) within MRSA by laser confocal microscopy and liquid chromatography-tandem MS method, suggesting the increased antibiotics accumulation might be related to the enhancement of AS on antibiotics. Furthermore, AS was found not to destroy the cell structure of MRSA by transmission electron microscope. AS was found to inhibit gene expressions of important efflux pumps such as NorA, NorB and NorC, but not MepA, SepA and MdeA. In conclusion, our results showed that AS was capable of enhancing the antibacterial activity of β-lactams via increasing antibiotic accumulations within MRSA through inhibiting gene expressions of efflux pumps such as NorA, NorB and NorC, but did not destroy the cell structure of MRSA. AS could be further investigated as a candidate drug for treatment of MRSA infection.
authors.affiliation: Department of Pharmacology, College of Pharmacy, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Jiang
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Xinchuan
authors.initials: X
authors.lastname: Zheng
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Xichun
authors.initials: X
authors.lastname: Pan
authors.forename: Rongxin
authors.initials: R
authors.lastname: Qing
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Cen
authors.forename: Jiang
authors.initials: J
authors.lastname: Zheng
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism; D003630:Daunorubicin / Q000494:pharmacology; D004357:Drug Synergism; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008826:Microbial Sensitivity Tests; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D010068:Oxacillin / Q000494:pharmacology*; D053719:Tandem Mass Spectrometry
chemical_list: D000900:Anti-Bacterial Agents; D037621:Artemisinins; D000077332:Artesunate; D001426:Bacterial Proteins; D003630:Daunorubicin; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010068:Oxacillin; C510398:MdeA protein, Staphylococcus aureus; C075040:NorA protein, Staphylococcus