Suga Takuya, Shiina Mayu, Asami Yukihiro, Iwatsuki Masato, Yamamoto Tsuyoshi, Nonaka Kenichi, Masuma Rokuro, Matsui Hidehito, Hanaki Hideaki, Iwamoto Susumu, Onodera Hideyuki, Shiomi Kazuro, Ōmura Satoshi
Department of Drug Discovery Sciences, Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan.
Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
J Antibiot (Tokyo). 2016 Aug;69(8):605-10. doi: 10.1038/ja.2016.70. Epub 2016 Jun 22.
Two new compounds, designated paraphaeosphaeride D (1) and berkleasmin F (2) together with a previously known compound, berkleasmin A (3), isolated from a culture broth of the fungus Paraphaeosphaeria sp. TR-022, proved to be new circumventors of arbekacin (ABK) resistance in methicillin-resistant Staphylococcus aureus (MRSA). The structures of 1 and 2 were elucidated by spectroscopic analyses, including various NMR experiments. All compounds showed 10-100 times ABK circumvention activities using the paper disc method and reduced the MIC values of ABK against MRSA from 16 μg ml(-1) to 4 μg ml(-1) (fourfold) using the agar dilution method. These new compounds might be promising lead compounds for developing circumventors of ABK resistance in MRSA.
从真菌拟暗球壳菌属TR - 022的培养液中分离出两种新化合物，分别命名为拟暗球壳菌素D（1）和伯克利斯明F（2），以及一种已知化合物伯克利斯明A（3），它们被证明是耐甲氧西林金黄色葡萄球菌（MRSA）中阿贝卡星（ABK）耐药性的新型规避剂。通过包括各种核磁共振实验在内的光谱分析阐明了1和2的结构。使用纸片法，所有化合物均显示出10 - 100倍的ABK规避活性，使用琼脂稀释法，它们将ABK对MRSA的最低抑菌浓度（MIC）值从16μg/ml降至4μg/ml（四倍）。这些新化合物可能是开发MRSA中ABK耐药性规避剂的有前景的先导化合物。
