Neofiscalin A and fiscalin C are potential novel indole alkaloid alternatives for the treatment of multidrug-resistant Gram-positive bacterial infections
Neofiscalin A and fiscalin C are potential novel indole alkaloid alternatives for the treatment of multidrug-resistant Gram-positive bacterial infections
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DOI：
10.1093/femsle/fnw150
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发表时间：
2016-08-01
影响因子：
2.1
通讯作者：
da Costa, Paulo Martins
中科院分区：
文献类型：
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作者：
Bessa, Lucinda J.;Buttachon, Suradet;da Costa, Paulo Martins
从海洋海绵共生真菌暹罗奈氏菌（Neaprotorya siamensis KUFA 0017）中分离得到10个吲哚生物碱。我们研究了这些化合物和以前从土壤真菌N. siamensis KUFC 6349.只有neofiscalin A对革兰氏阳性菌，包括耐甲氧西林金黄色葡萄球菌（MRSA）和耐万古霉素粪肠球菌（VRE）显示出抗菌活性;对这两种菌株的最小抑菌浓度（MIC）为8 μ g mL（-1）。另一种化合物，fiscalin C，当与苯唑西林组合时，呈现出对MRSA的协同活性，尽管单独没有显示出抗菌作用。此外，neofiscalin A，当存在于亚MIC时，阻碍MRSA和VRE菌株形成生物膜的能力。此外，新非斯卡林A对MRSA和VRE分离株的生物膜抑制浓度值分别为96和80 μ g mL（-1）。在200 μ g/mL的浓度下，neofiscalin A能够将生物膜的代谢活性降低约50%。一个重要的事实是，我们的研究结果还表明，neofiscalin A对人脑毛细血管内皮细胞系没有细胞毒性。
Ten indole alkaloids were obtained from the marine sponge-associated fungus Neosartorya siamensis KUFA 0017. We studied the antimicrobial properties of these and of three other compounds previously isolated from the soil fungus N. siamensis KUFC 6349. Only neofiscalin A showed antimicrobial activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE); with a minimum inhibitory concentration (MIC) of 8 mu g mL(-1) against both strains. Another compound, fiscalin C, presented synergistic activity against MRSA when combined with oxacillin, although alone showed no antibacterial effect. Moreover, neofiscalin A, when present at sub-MICs, hampered the ability of both MRSA and VRE strains to form a biofilm. Additionally, the biofilm inhibitory concentration values of neofiscalin A against the MRSA and VRE isolates were 96 and 80 mu g mL(-1), respectively. At a concentration of 200 mu g mL(-1), neofiscalin A was able to reduce the metabolic activity of the biofilms by similar to 50%. One important fact is that our results also showed that neofiscalin A had no cytotoxicity against a human brain capillary endothelial cell line.