Inactivation of arbekacin by aminoglycoside-modifying enzymes from arbekacin-resistant strains of methicillin-resistant Staphylococcus aureus

S. Fujimura, Y. Tokue, H. Takahashi, T. Nukiwa, Akira Watanabe

    Research output: Contribution to journalArticlepeer-review

    Abstract

    A novel pathway of arbekacin (ABK) acetylation was found in four ABK- resistant clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA), as well as one strain of MRSA that had acquired resistance to ABK in vitro, one strain of ABK-resistant strain of MRSA including the bifunctional AAC (6')-APH (2'), and an ABK-susceptible strain of MRSA. Analysis of the ABK metabolites in suspension cultures of ABK-resistant MRSA by 1H, 13C- nuclear magnetic resonance, high-resolution mass spectrometry and Fourier transform infrared spectrometry detected the (S)-4-amino-2-hydroxybutyryl (AHB) group in ABK, while only unmetabolized ABK was detected in suspension culture of the ABK-susceptible MRSA. The cell lysate of the ABK-resistant MRSA exhibited only acetylation without phosphorylation. This acetylation activity was attributed to a 28 kDa enzyme detected in all the ABK-resistant but not in ABK-susceptible MRSA by gel permeation chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the bacterial cell lysate. This enzyme has AAC (4''') activity. The N-terminal amino acid sequence of this enzyme had proteins which showed a strong similarity (>90 identity over 30 amino acid) to the ABK modifying enzyme AAC (6') -APH (2'). These results suggest that this enzyme is a mutant and/or degradation protein of AAC (6') -APH (2').

    Original languageEnglish
    Pages (from-to)1-8
    Number of pages8
    JournalJapanese Journal of Chemotherapy
    Volume47
    Issue number1
    Publication statusPublished - 1999 Jan 1

    Keywords

    • AAC (4''')
    • Arbekacin
    • Arbekacin-resistance
    • MRSA

    ASJC Scopus subject areas

    • Pharmacology
    • Pharmacology (medical)

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