Yagi Akiho, Sato Mayu, Kikuchi Katsuki, Taniguchi Akito, Fukuda Takashi, Uchida Ryuji
Division of Natural Product Chemistry, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, Japan.
Department of Fisheries, Faculty of Agriculture, Kindai University, Nara, Japan.
J Antibiot (Tokyo). 2025 Jun 11. doi: 10.1038/s41429-025-00838-3.
The screening of antibiotics derived from microbial resources to combat vancomycin-resistant enterococci (VRE) revealed that a culture of marine-derived Peribacillus sp. KDM594 exhibited significant therapeutic efficacy in an infected in vivo-mimic silkworm model. Bioassay-guided purification led to the isolation of micrococcins P1 (1) and P2 (2), which exhibited potent antimicrobial activities against Gram-positive bacteria, including VRE, methicillin-resistant Staphylococcus aureus (MRSA), and Mycobacterium spp., with MIC values ranging from 0.25 to 8.0 µg ml using the microdilution method. In the silkworm models infected with VRE or MRSA, 1 and 2 exerted moderate therapeutic effects, with ED values ranging from 3.2 to 51 µg larva g. Furthermore, a pharmacokinetic analysis revealed that 2 was metabolized to 1 in the silkworm hemolymph, and their elimination half-lives were 3.2 and 3.0 h, respectively. These results suggest that micrococcins are promising lead compounds for the development of anti-VRE and MRSA drugs.
对源自微生物资源的抗生素进行筛选以对抗耐万古霉素肠球菌（VRE），结果显示，一株海洋来源的类芽孢杆菌属Peribacillus sp. KDM594培养物在感染的体内模拟家蚕模型中表现出显著的治疗效果。通过生物测定指导的纯化方法，分离出了微球菌素P1（1）和P2（2），它们对革兰氏阳性菌具有强大的抗菌活性，包括VRE、耐甲氧西林金黄色葡萄球菌（MRSA）和分枝杆菌属，采用微量稀释法时，其最低抑菌浓度（MIC）值范围为0.25至8.0μg/ml。在感染VRE或MRSA的家蚕模型中，1和2发挥了适度的治疗作用，半数有效剂量（ED）值范围为3.2至51μg/幼虫g。此外，药代动力学分析表明，2在家蚕血淋巴中代谢为1，它们的消除半衰期分别为3.2小时和3.0小时。这些结果表明，微球菌素是开发抗VRE和MRSA药物的有前景的先导化合物。
