{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1390282679129189248.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.7164/antibiotics.57.679"}},{"identifier":{"@type":"COI","@value":"1:CAS:528:DC%2BD2cXptlOgtro%3D"}},{"identifier":{"@type":"PMID","@value":"15638329"}},{"identifier":{"@type":"NAID","@value":"130003504130"}},{"identifier":{"@type":"NAID","@value":"10013726971"}},{"identifier":{"@type":"URI","@value":"https://search.jamas.or.jp/link/ui/2006100165"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@language":"en","@value":"Characterization of a Bifunctional Aminoglycoside-Modifying Enzyme with Novel Substrate Specificity and Its Gene from a Clinical Isolate of Methicillin-Resistant Staphylococcus aureus with High Arbekacin Resistance"}],"dc:language":"en","description":[{"type":"abstract","notation":[{"@language":"en","@value":"A clinical isolate (designated PRC104) of methicillin-resistant <i>Staphylococcus aureus</i> was discovered with a novel aminoglycoside resistance profile, including unusually high resistance (MIC 128μg/ml) to arbekacin (an effective anti-MRSA drug in Japan). We characterized the activity and gene of its bifunctional aminoglycoside-modifying enzyme, AAC(6')/APH(2\"), in comparison with those of a regular one that has been known as the critical resistance basis to both gentamicin and arbekacin in methicillin-resistant <i>Staphylococcus aureus</i>. The <i>aac(6')/aph(2\")</i> gene of strain PRC104 contained a single base alteration at a novel site (G 1126A) resulting in one amino acid substitution (S376N) in the phosphorylation catalytic motif. The phosphorylation activity of the PRC104 enzyme was enhanced for arbekacin and reduced for gentamicin. Both strain PRC104 and <i>S. aureus</i> RN4220 containing the cloned gene were identical in terms of the substrate specificity of the enzyme as well as the aminoglycoside resistance profile, although both mRNA and aminoglycoside resistance levels were markedly high in strain PRC104. Therefore, the cloned <i>aac(6')/aph(2\")</i> gene may represent the molecular basis for the novel aminoglycoside modification capability as well as novel aminoglycoside resistance profile of <i>S. aureus</i> PRC104."}],"abstractLicenseFlag":"disallow"}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1420564276163874432","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"50332359"},{"@type":"NRID","@value":"1000050332359"},{"@type":"NRID","@value":"9000279905830"},{"@type":"NRID","@value":"9000263046056"},{"@type":"NRID","@value":"9000347076730"},{"@type":"NRID","@value":"9000004711750"},{"@type":"NRID","@value":"9000412278155"},{"@type":"NRID","@value":"9000001329199"},{"@type":"NRID","@value":"9000288830094"},{"@type":"NRID","@value":"9000000171919"},{"@type":"NRID","@value":"9000010288887"},{"@type":"NRID","@value":"9000253088610"},{"@type":"NRID","@value":"9000412230304"},{"@type":"NRID","@value":"9000279911961"},{"@type":"NRID","@value":"9000415346981"},{"@type":"NRID","@value":"9000326653151"},{"@type":"NRID","@value":"9000321410122"},{"@type":"NRID","@value":"9000384274610"},{"@type":"NRID","@value":"9000281371948"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/k_ishino3"}],"foaf:name":[{"@language":"en","@value":"ISHINO KEIKO"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Bioactive Molecules, National Institute of Infectious Diseases"}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679129189250","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000253088611"}],"foaf:name":[{"@language":"en","@value":"ISHIKAWA JUN"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Bioactive Molecules, National Institute of Infectious Diseases"}]},{"@id":"https://cir.nii.ac.jp/crid/1030003658453324288","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"60159639"},{"@type":"NRID","@value":"1000060159639"},{"@type":"NRID","@value":"9000363958582"},{"@type":"NRID","@value":"9000024161217"},{"@type":"NRID","@value":"9000004407260"},{"@type":"NRID","@value":"9000022825635"},{"@type":"NRID","@value":"9000258037190"},{"@type":"NRID","@value":"9000022539243"},{"@type":"NRID","@value":"9000014580843"},{"@type":"NRID","@value":"9000283534144"},{"@type":"NRID","@value":"9000256790823"},{"@type":"NRID","@value":"9000253088612"},{"@type":"NRID","@value":"9000402583038"}],"foaf:name":[{"@language":"en","@value":"IKEDA YOKO"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Microbial Chemistry Research Center"}]},{"@id":"https://cir.nii.ac.jp/crid/1410001204151391618","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000000075076"},{"@type":"NRID","@value":"9000253087479"},{"@type":"NRID","@value":"9000253088613"},{"@type":"NRID","@value":"9000257986709"}],"foaf:name":[{"@language":"en","@value":"HOTTA KUNIMOTO"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Bioactive Molecules, National Institute of Infectious Diseases"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00218820"},{"@type":"EISSN","@value":"18811469"},{"@type":"NCID","@value":"AA0069330X"}],"prism:publicationName":[{"@language":"en","@value":"The Journal of Antibiotics"},{"@language":"en","@value":"J. Antibiot."}],"dc:publisher":[{"@language":"en","@value":"JAPAN ANTIBIOTICS RESEARCH ASSOCIATION"},{"@language":"ja","@value":"公益財団法人 日本感染症医薬品協会"}],"prism:publicationDate":"2004","prism:volume":"57","prism:number":"10","prism:startingPage":"679","prism:endingPage":"686"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","url":[{"@id":"https://search.jamas.or.jp/link/ui/2006100165"}],"availableAt":"2004","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Staphylococcus%20aureus","dc:title":"Staphylococcus aureus"},{"@id":"https://cir.nii.ac.jp/all?q=Molecular%20Sequence%20Data","dc:title":"Molecular Sequence Data"},{"@id":"https://cir.nii.ac.jp/all?q=Dibekacin","dc:title":"Dibekacin"},{"@id":"https://cir.nii.ac.jp/all?q=Substrate%20Specificity","dc:title":"Substrate Specificity"},{"@id":"https://cir.nii.ac.jp/all?q=Aminoglycosides","dc:title":"Aminoglycosides"},{"@id":"https://cir.nii.ac.jp/all?q=Drug%20Resistance,%20Bacterial","dc:title":"Drug Resistance, Bacterial"},{"@id":"https://cir.nii.ac.jp/all?q=Humans","dc:title":"Humans"},{"@id":"https://cir.nii.ac.jp/all?q=Methicillin%20Resistance","dc:title":"Methicillin Resistance"},{"@id":"https://cir.nii.ac.jp/all?q=Amino%20Acid%20Sequence","dc:title":"Amino Acid Sequence"},{"@id":"https://cir.nii.ac.jp/all?q=RNA,%20Messenger","dc:title":"RNA, Messenger"},{"@id":"https://cir.nii.ac.jp/all?q=Phosphorylation","dc:title":"Phosphorylation"}],"project":[{"@id":"https://cir.nii.ac.jp/crid/1040000781809921024","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"15510187"},{"@type":"JGN","@value":"JP15510187"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15510187/"}],"notation":[{"@language":"ja","@value":"微生物代謝産物を用いた特異的酸性スフィンゴミエリナーゼ阻害剤の探索"},{"@language":"en","@value":"Screening for selective acidic sphyngomyelinase inhibitor using microbial product"}]}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360004232524822400","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Biverlactones A–D, new circumventors of arbekacin resistance in MRSA, produced by Penicillium sp. 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The role of ASP-99 as an active site base important for acetyl transfer"}]},{"@id":"https://cir.nii.ac.jp/crid/1571417126662903680","@type":"Article","relationType":["cites"]},{"@id":"https://cir.nii.ac.jp/crid/1571698599853151360","@type":"Article","relationType":["cites"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Syntheses of 1-N-(S)-4-amino-2-hydroxybutyryl)-kanamycin B and -3', 4'-dideoxykanamycin B active against kanamycin-resistant bacteria"}]},{"@id":"https://cir.nii.ac.jp/crid/1571698600506854528","@type":"Article","relationType":["isCitedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Trends in the gentamicin and arbekacin susceptibility of methicillin-resistant Staphylococcus aureus and the genes encoding aminoglycoside-modifying enzymes"}]},{"@id":"https://cir.nii.ac.jp/crid/1572543024534021632","@type":"Article","relationType":["cites"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Double Stage Activity in Aminoglycoside Antibiotics"}]},{"@id":"https://cir.nii.ac.jp/crid/1572543026584658816","@type":"Article","relationType":["cites"],"jpcoar:relatedTitle":[{"@language":"en","@value":"A newly recognized acetylated metabolite of arbekacin in arbekacin-resistant strains of methicillin-resistant Staphylococcus aureus"}]},{"@id":"https://cir.nii.ac.jp/crid/1572543026622425088","@type":"Article","relationType":["cites"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Molecular mechanism for the enhancement of arbekacin resistance in a methicillin-resistant Staphylococcus aureus"}]},{"@id":"https://cir.nii.ac.jp/crid/1572824501514651264","@type":"Article","relationType":["cites"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Purification and characterization of Aminoglycoside-modifying enzymes from Staphylococcus aureus and Staphylococcus epidermidis"}]},{"@id":"https://cir.nii.ac.jp/crid/1573387449510795008","@type":"Article","relationType":["cites"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Semisynthetic aminoglycoside antibiotics : Development and enzymatic modifications"}]},{"@id":"https://cir.nii.ac.jp/crid/1573387450036157568","@type":"Article","relationType":["isCitedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Trends of Arbekacin-resistant MRSA Strains in Japanese Hospitals (1979 to 2000)"}]},{"@id":"https://cir.nii.ac.jp/crid/1573950401407580288","@type":"Article","relationType":["cites"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Nucleotide sequence analysis of the gene specifying the bifunctional 6'-aminoglycoside acetyltransferase 2\"-aminoglycoside phosphtransferase enzyme in Streptococcus faecalis and identification and cloning of gene regions specifying the two activities"}]},{"@id":"https://cir.nii.ac.jp/crid/1573950401407662208","@type":"Article","relationType":["cites"],"jpcoar:relatedTitle":[{"@language":"en","@value":"The aacA-aphD gentamicin and kanamycin resistance determinant of Tn4001 from Staphylococcus aureus : expression and nucleotide sequence analysis"}]},{"@id":"https://cir.nii.ac.jp/crid/1574231874786760960","@type":"Article","relationType":["cites"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Novel arbekacin- and amikacin-modifying enzyme of methicillin-resistant Staphylococcus aureus"}]},{"@id":"https://cir.nii.ac.jp/crid/1574231875886667008","@type":"Article","relationType":["isCitedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Aranorosin circumvents arbekacin-resistance in MRSA by inhibiting the bifunctional enzyme AAC(6')/APH(2\")"}]}],"dataSourceIdentifier":[{"@type":"JALC","@value":"oai:japanlinkcenter.org:0024395201"},{"@type":"CROSSREF","@value":"10.7164/antibiotics.57.679"},{"@type":"CIA","@value":"10013726971"},{"@type":"CIA","@value":"130003504130"},{"@type":"KAKEN","@value":"PRODUCT-18249893"},{"@type":"OPENAIRE","@value":"doi_dedup___::24798c024dd84d1659cfc38b4ec3b800"},{"@type":"CROSSREF","@value":"10.1038/ja.2017.7_references_DOI_6CVHSCAZch1OliME4FZdMiojO0n"},{"@type":"CROSSREF","@value":"10.1128/aac.01062-13_references_DOI_6CVHSCAZch1OliME4FZdMiojO0n"},{"@type":"CROSSREF","@value":"10.1016/j.tet.2011.05.061_references_DOI_6CVHSCAZch1OliME4FZdMiojO0n"},{"@type":"CROSSREF","@value":"10.1038/ja.2012.53_references_DOI_6CVHSCAZch1OliME4FZdMiojO0n"},{"@type":"CROSSREF","@value":"10.1021/ol401975z_references_DOI_6CVHSCAZch1OliME4FZdMiojO0n"}]}