Novel Bacterial Metabolite Merochlorin A Demonstrates in vitro Activity against Multi-Drug Resistant Methicillin-Resistant Staphylococcus aureus 英文参考文献.docVIP

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Novel Bacterial Metabolite Merochlorin A Demonstrates in vitro Activity against Multi-Drug Resistant Methicillin-Resistant Staphylococcus aureus 英文参考文献.doc

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Novel Bacterial Metabolite Merochlorin A Demonstrates in vitro Activity against Multi-Drug Resistant Methicillin-Resistant Staphylococcus aureus 英文参考文献

NovelBacterialMetaboliteMerochlorinADemonstrates invitroActivityagainstMulti-DrugResistantMethicillin- ResistantStaphylococcusaureus GeorgeSakoulas1*,Sang-JipNam2,SandraLoesgen2,WilliamFenical2,3,PaulR.Jensen2,VictorNizet1,3, MaryHensler1,3 1DepartmentofPediatrics,SchoolofMedicine,UniversityofCaliforniaSanDiego,LaJolla,California,UnitedStatesofAmerica,2CenterforMarineBiotechnologyand Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California, United States of America, 3School of Pharmacy and PharmaceuticalSciences,SchoolofMedicine,UniversityofCaliforniaSanDiego,LaJolla,California,UnitedStatesofAmerica Abstract Background: We evaluated the in vitro activity of a merochlorin A, a novel compound with a unique carbon skeleton, against a spectrum of clinically relevant bacterial pathogens and against previously characterized clinical and laboratory Staphylococcusaureusisolateswithresistancetonumerousantibiotics. Methods:MerochlorinAwasisolatedandpurifiedfromamarine-derivedactinomycetestrainCNH189.Susceptibilitytesting formerochlorinAwasperformedagainstpreviouslycharacterizedhumanpathogensusingbrothmicrodilutionandagar dilution methods. Cytotoxicity was assayed in tissue culture assays at 24 and 72hours against human HeLa and mouse sarcomaL929celllines. Results: The structure of as new antibiotic, merochlorin A, was assigned by comprehensive spectroscopic analysis. MerochlorinAdemonstratedinvitroactivityagainstGram-positivebacteria,includingClostridiumdificile,butnotagainst Gramnegativebacteria.InS.aureus,susceptibilitywasnotaffectedbyribosomalmutationsconferringlinezolidresistance, mutations in dlt or mprF conferring resistance to daptomycin, accessory gene regulator knockout mutations, or the developmentofthevancomycin-intermediateresistantphenotype.MerochlorinAdemonstratedrapidbactericidalactivity againstMRSA.Activitywaslostinthepresenceof20%serum. Conclusions: The unique meroterpenoid, merochlorin A demonstrated excellen