Molecular mechanism for the enhancement of arbekacin resistance in a methicillin‐resistant Staphylococcus aureus

FEBS Letters

Sugiyama, Masanori²  Matsuo, Hiroaki²  Kumagai, Takanori²  Kuwabara, Masao¹  Kobayashi, Miho² 

[1] Hiroshima Prefectural Hospital, Ujinakanda 1-5-54, Minami-ku, Hiroshima 734-8530, Japan;Department of Molecular Microbiology and Biotechnology, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan

关键词: aacA;    Aminoglycoside antibiotic-inactivating enzyme;    aphD;    Arbekacin resistance;    Methicillin-resistant Staphylococcus aureus;    AAC;    aminoglycoside antibiotic acetyltransferase;    Abk;    arbekacin;    APH;    aminoglycoside antibiotic phosphotransferase;    Bm;    bleomycin;    CAT;    chloramphenicol acetyltransferase;    Dbk;    dibekacin;    DTT;    dithiothreitol;    Gm;    gentamicin;    MIC;    minimum inhibitory concentration;    MRSA;    methicillin-resistant Staphylococcus aureus;    MSSA;    methicillin-sensitive Staphylococcus aureus;   

DOI  :  10.1016/S0014-5793(03)00644-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown