Chemoinformatics-assisted development of new anti-biofilm compounds
Chemoinformatics-assisted development of new anti-biofilm compounds
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DOI：
10.1007/s00253-010-2471-0
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发表时间：
2010-06-01
影响因子：
5
通讯作者：
Klemm, Per
中科院分区：
文献类型：
--
作者：
Durig, Anna;Kouskoumvekaki, Irene;Klemm, Per
细菌生物膜与大量感染有关。生物膜中的细菌对抗生素特别有抵抗力，因此很难根除与生物膜相关的感染。在这里，我们使用一种结合微生物学和化学信息学的新颖的跨学科方法来识别新型有效的抗生物膜药物。我们发现鞣花酸（存在于绿茶中）显着抑制停乳链球菌生物膜的形成。基于鞣花酸，我们对中国天然产物数据库进行了计算机筛选，以预测具有相似特征的第二代化合物列表。其中一种，七叶亭，被证明可以更有效地防止金黄色葡萄球菌形成生物膜。从七叶亭中预测出第三代化合物列表。其中一种非瑟酮比两种母体化合物更能消除生物膜的形成。非瑟酮显着抑制金黄色葡萄球菌和停乳链球菌的生物膜形成。这些化合物在影响生物膜形成的浓度下不会影响浮游生物的生长，并且似乎是生物膜的特异性拮抗剂。可以说，由于这三种化合物都是食用植物的天然成分，因此人类对它们的耐受性应该很好。我们的研究结果表明，这种具有改变细菌生活方式的小型植物成分是新一代抗菌药物的有希望的候选者。该研究强调了化学信息学和生物膜研究相结合的潜力。
Bacterial biofilms are associated with a large number of infections. Biofilm-dwelling bacteria are particularly resistant to antibiotics, making it hard to eradicate biofilm-associated infections. Here, we use a novel cross-disciplinary approach combining microbiology and chemoinformatics to identify new and efficient anti-biofilm drugs. We found that ellagic acid (present in green tea) significantly inhibited biofilm formation of Streptococcus dysgalactiae. Based on ellagic acid, we performed in silico screening of the Chinese Natural Product Database to predict a 2nd-generation list of compounds with similar characteristics. One of these, esculetin, proved to be more efficient in preventing biofilm formation by Staphylococcus aureus. From esculetin a 3rd-generation list of compounds was predicted. One of them, fisetin, was even better to abolish biofilm formation than the two parent compounds. Fisetin dramatically inhibited biofilm formation of both S. aureus and S. dysgalactiae. The compounds did not affect planktonic growth in concentrations where they affected biofilm formation and appeared to be specific antagonists of biofilms. Arguably, since all three compounds are natural ingredients of dietary plants, they should be well-tolerated by humans. Our results indicate that such small plant components, with bacterial lifestyle altering properties are promising candidates for novel generations of antimicrobial drugs. The study underlines the potential in combining chemoinformatics and biofilm research.