Zhu C B, Sunada A, Ishikawa J, Ikeda Y, Kondo S, Hotta K
Department of Bioactive Molecules, National Institute of Infectious Diseases, Tokyo.
J Antibiot (Tokyo). 1999 Oct;52(10):889-94. doi: 10.7164/antibiotics.52.889.
From a rare actinomycete strain #8 isolated from soil as arbekacin (ABK) resistant, we cloned a gene segment (0.9 kb) conferring multiple resistance to aminoglycoside (AG) antibiotics with 6'-NH2 including semisynthetic ones except ABK and neomycin (NM). Enzymatic modification using cell free extracts from Streptomyces lividans TK21/pANT-S2 carrying the cloned gene revealed that the gene coded for an AG 6'-acetyltransferase [AAC(6')] capable of acetylating all of the tested AGs with 6'-NH2 including semisynthetic ones and astromicin. The substrate specificity of the enzyme was thus similar to that of AAC(6')-Ie of Enterococcus faecalis. Antibiotic assay revealed a weak but clear antibiotic activity of 6'-N-acetylABK (8% of ABK activity) in contrast with substantial inactivation by the AAC(6') of the other AGs including amikacin and isepamicin. The NM acetylation by the AAC(6') also did not result in NM inactivation. It seems thus likely that AAC(6')-dependent resistance to ABK and NM, if it emerges, will remain at low level.
从一株从土壤中分离得到的对阿贝卡星（ABK）具有抗性的罕见放线菌菌株#8中，我们克隆了一个基因片段（0.9 kb），该片段赋予对包括除ABK和新霉素（NM）之外的含6'-NH2的氨基糖苷（AG）抗生素（包括半合成抗生素）的多重抗性。使用携带克隆基因的变铅青链霉菌TK21/pANT-S2的无细胞提取物进行酶促修饰，结果表明该基因编码一种AG 6'-乙酰转移酶[AAC(6')]，能够乙酰化所有测试的含6'-NH2的AGs，包括半合成AGs和阿司米星。因此，该酶的底物特异性与粪肠球菌的AAC(6')-Ie相似。抗生素检测显示，与包括阿米卡星和异帕米星在内的其他AGs被AAC(6')大量失活形成对比，6'-N-乙酰ABK具有较弱但明显的抗生素活性（为ABK活性的8%）。AAC(6')对NM的乙酰化也未导致NM失活。因此，如果出现依赖AAC(6')的对ABK和NM的抗性，似乎可能会保持在较低水平。
