title: Novel arbekacin- and amikacin-modifying enzyme of methicillin-resistant Staphylococcus aureus.
abstract: An aminoglycoside-modifying enzyme in arbekacin-resistant methicillin-resistant Staphylococcus aureus (MRSA), exhibiting 4'''-N-acetylation, was examined. Although the MRSA strain with AAC(4''') had no AAC(6')-APH(2") activity, a DNA fragment of the AAC(6')-APH(2") gene was amplified by PCR and the purified N-terminal 30-amino acid sequence of this AAC(4''') was identical to AAC(6')-APH(2"). Direct DNA sequencing of this 'silent' AAC(6')-APH(2") gene revealed a single point mutation leading to a substitution of Gly for Asp80, through which the secondary structure is affected. A change in protein conformation could lead to a cleavage and a change of the enzymatic activity. We propose a new aminoglycoside-resistance mediated by AAC(4''') is caused by a mutation-modified AAC(6')-APH(2").
authors.affiliation: Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan. hujimura@mail.sp.myu.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Fujimura
authors.forename: Y
authors.initials: Y
authors.lastname: Tokue
authors.forename: H
authors.initials: H
authors.lastname: Takahashi
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.forename: K
authors.initials: K
authors.lastname: Gomi
authors.forename: T
authors.initials: T
authors.lastname: Abe
authors.forename: T
authors.initials: T
authors.lastname: Nukiwa
authors.forename: A
authors.initials: A
authors.lastname: Watanabe
mesh_terms: D000123:Acetyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000583:Amikacin / Q000494:pharmacology*; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003982:Dibekacin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D006801:Humans; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology*
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D003982:Dibekacin; D000583:Amikacin; C108453:6'-aminoglycoside acetyltransferase-2''-aminoglycoside phosphotransferase; D000123:Acetyltransferases; C019681:aminoglycoside acetyltransferase; D017853:Phosphotransferases (Alcohol Group Acceptor); C031986:arbekacin