Screening of natural compounds identifies ferutinin as an antibacterial and anti-biofilm compound

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 <i>Staphylococcus aureus</i> 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 <i>S. aureus</i>. 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 <i>S. aureus</i> biofilms.

当前抗菌筛选大多以浮游细菌（planktonic bacteria）为靶标，但针对作用于生物膜（biofilm）的活性物质的探索研究投入相对匮乏。本研究采用384孔板平台，针对金黄色葡萄球菌（Staphylococcus aureus）筛选天然化合物库，以筛选出可抑制生物膜形成的化合物。本研究共获得5种结构各异的命中化合物，依次为厚朴酚（honokiol）、奇曼吉定（tschimganidin）、铁杉酯素（ferutinin）、冬凌草甲素（oridonin）与脱氧紫草素（deoxyshikonin），并选取这些化合物开展后续研究。针对不同细菌菌种，我们评估了这些化合物抑制与破坏生物膜的能力，同时考察了其诱发耐药性的潜力与细胞毒性。其中铁杉酯素展现出最优的抗菌活性：针对金黄色葡萄球菌（Staphylococcus aureus），其最低抑菌浓度、最低杀菌浓度与生物膜抑制浓度均为25 μM。该化合物可有效破坏已形成的生物膜（活菌数降幅超过5个对数级），并在中性粒细胞（neutrophils）存在的条件下，减少导管表面生物膜的形成。本研究为5种天然化合物的抗菌活性提供了新的实验数据，并确认铁杉酯素是对抗金黄色葡萄球菌生物膜的极具潜力的候选化合物。