title: Molecular mechanism for the enhancement of arbekacin resistance in a methicillin-resistant Staphylococcus aureus.
abstract: We have clinically isolated a methicillin-resistant Staphylococcus aureus (MRSA) K-1 which exhibits enhanced arbekacin (Abk) resistance. In this study, we investigated a molecular mechanism for the overproduction of a bifunctional enzyme catalyzing both 2"-O-phosphorylation and 6'-N-acetylation of aminoglycoside antibiotics that is encoded by aacA-aphD and designated [AAC(6')/APH(2")] and is expressed in MRSA K-1. The sequence analysis of the 5'-adjacent region of the aacA-aphD structural gene in MRSA K-1 showed that 12 bp are deleted from the aacA-aphD promoter region when compared with that in MRSA B-26, which exhibits lower resistance to Abk than K-1. By artificially deleting the 12 bp from the corresponding region in MRSA B-26, we confirmed that the strain increases Abk resistance to the same level as seen in MRSA K-1, which suggests that the 12 bp deletion from the 5'-adjacent region of the aacA-aphD structural gene created a strong promoter to overexpress the bifunctional enzyme.
authors.affiliation: Department of Molecular Microbiology and Biotechnology, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsuo
authors.forename: Miho
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Takanori
authors.initials: T
authors.lastname: Kumagai
authors.forename: Masao
authors.initials: M
authors.lastname: Kuwabara
authors.forename: Masanori
authors.initials: M
authors.lastname: Sugiyama
mesh_terms: D000107:Acetylation; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001483:Base Sequence; D015152:Blotting, Northern; D002384:Catalysis; D017931:DNA Primers; D004269:DNA, Bacterial; D003982:Dibekacin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005798:Genes, Bacterial; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D012689:Sequence Homology, Nucleic Acid; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D017931:DNA Primers; D004269:DNA, Bacterial; D003982:Dibekacin; C031986:arbekacin