Abstract

Antibacterial screenings are most commonly targeted at planktonic bacteria but less effort is dedicated to the exploration of agents acting on biofilms. Here, a natural compounds library was screened against Staphylococcus aureus using a 384-well plate platform to identify compounds preventing biofilm formation. Five structurally diverse hits were selected for follow-up studies: honokiol, tschimganidin, ferutinin, oridonin and deoxyshikonin. The compounds were evaluated against different bacterial species for their capacity to prevent and disrupt biofilms. The development of resistance and cytotoxicity were also investigated. Ferutinin displayed the best antibacterial activity, with a minimum inhibitory, bactericidal and biofilm preventive concentration of 25 µM against S. aureus. It efficiently disrupted pre-formed biofilms (over 5-log reduction of viable cells) and reduced biofilm formation on a catheter in the presence of neutrophils. This work provides new information on the antibacterial activity of five natural compounds and identified ferutinin as a promising candidate against S. aureus biofilms.

摘要

抗菌筛选最常针对浮游细菌，但较少致力于探索作用于生物膜的药剂。在这里，使用 384 孔板平台针对金黄色葡萄球菌筛选天然化合物库，以鉴定防止生物膜形成的化合物。选择了五种结构不同的命中物进行后续研究：和厚朴酚、tschimganidin、ferutinin、oridonin 和 deoxyshikonin。这些化合物针对不同细菌种类的预防和破坏生物膜的能力进行了评估。还研究了抗性和细胞毒性的发展。Ferutinin 表现出最好的抗菌活性，对金黄色葡萄球菌的最低抑制、杀菌和生物膜预防浓度为 25 µM. 它有效地破坏了预先形成的生物膜（活细胞减少了 5-log 以上），并在中性粒细胞存在的情况下减少了导管上生物膜的形成。这项工作提供了有关五种天然化合物抗菌活性的新信息，并确定了 ferutinin 是一种有希望的抗金黄色葡萄球菌生物膜候选物。