title: The direct anti-MRSA effect of emodin via damaging cell membrane.
abstract: Methicillin-resistant Staphylococcus aureus (MRSA) has become an important bacterium for nosocomial infection. Only a few antibiotics can be effective against MRSA. Therefore, searching for new drugs against MRSA is important. Herein, anti-MRSA activities of emodin and its mechanisms were investigated. Firstly, in vitro antimicrobial activity was investigated by minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and time-growth curve, and multipassage resistance testing was performed. Secondly, protection of emodin on mice survival and blood bacterial load in mice challenged with lethal or sublethal dose of MRSA were investigated. Subsequently, the influences of emodin on the bacterial morphology, messenger RNA (mRNA) expressions related to cell wall synthesis and lysis, β-lactamase activity, drug accumulation, membrane fluidity, and integrity were performed to investigate its mechanisms. Lastly, in vitro cytotoxicity assay were performed using the 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) method. The results showed MICs and MBCs of emodin against MRSA252 and 36 clinical MRSA strains were among 2-8 and 4-32 μg/mL, respectively. There was no MIC increase for emodin during 20 passages. In vivo, emodin dose-dependently protected mice challenged with lethal dose of MRSA and decreased bacterial load in mice challenged with sublethal dose of MRSA. Morphology observation showed emodin might disrupt cell wall and membrane of MRSA. Although emodin had no influence on genes related to cell wall synthesis and lysis as well as β-lactamase activity and drug accumulation, emodin reduced membrane fluidity and disrupted membrane integrity. Based on the fact that emodin had no significant cytotoxicity against mammalian cells, it could be further investigated as a membrane-damage bactericide against MRSA in the future.
authors.affiliation: Department of Pharmacology, College of Pharmacy, Third Military Medical University, Chongqing, 400038, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Peng
authors.forename: Rongxin
authors.initials: R
authors.lastname: Qin
authors.forename: Zifei
authors.initials: Z
authors.lastname: Yan
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Cen
authors.forename: Xinchuan
authors.initials: X
authors.lastname: Zheng
authors.forename: Xichun
authors.initials: X
authors.lastname: Pan
authors.forename: Weiwei
authors.initials: W
authors.lastname: Jiang
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002462:Cell Membrane / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial; D004642:Emodin / Q000494:pharmacology* / Q000627:therapeutic use; D008264:Macrophages / Q000187:drug effects; D008560:Membrane Fluidity / Q000187:drug effects; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D051379:Mice; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D000067996:RAW 264.7 Cells; D012692:Serial Passage; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D004642:Emodin