TERI-Deakin Nanobiotechnology Centre, The Energy and Resources Institute, TERI Gram, Gurgaon, Haryana, 122101, India.
TERI-Deakin Nanobiotechnology Centre, The Energy and Resources Institute, TERI Gram, Gurgaon, Haryana, 122101, India.
Microb Pathog. 2021 Jan;150:104676. doi: 10.1016/j.micpath.2020.104676. Epub 2020 Dec 3.
Lichens are known to be useful and important in ethanopharmacology since ages and still possess substantial interest in alternative medical practices around the world. The intent of this investigation was to evaluate and to understand the antibacterial potential of usnic acid which was isolated from Himalyan fruticose lichen Ramalina roesleri. Usnic acid is predicted for its pharmaceutical properties through in -silico studies. Binding efficiency of usnic acid with Penicillin binding protein-PBP2a, a protein which is responsible for conferring resistance in Staphylococcus aureus was accessed using in-silico interaction assays comparing with oxacillin and ceftaroline. Further, the validation of in-silico modelling was checked by determining the antibacterial potential of usnic acid against methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates. In total, 28 clinical isolates collected from hospitals/medical students were included in the study and the anti-Staphylococcal activity was determined using agar plate dilution method followed by time-kill kinetics and synergistic studies. The scanning electron microscopic (SEM) pictures were obtained to show the cell wall disruption of MRSA by usnic acid. Docking results clearly indicated the enhanced binding potential of usnic acid (Glide XP G Score: 10.968; Glide energy -64.869) with PBP2a which is better than the energy range of reference compound, oxacillin (Glide XP G Score: 6.596; Glide energy -53.285) and roughly comparable to the co-crystallized ligand ceftaroline (Glide XP G Score: 12.20; Glide energy -70.322). Cefteroline is known to be more active against MRSA compared to oxacillin. The minimum inhibitory concentrations (MICs) of usnic acid against the clinical isolates of MRSA and reference strain (NCTC-6571) were in the range of 32-128 μg/ml. The high affinity of usnic acid to bind with PBP2a which is demonstrated via in-silico studies is further confirmed by the impressive inhibitory activity of usnic acid on MRSA clinical isolates.
地衣在药用植物学中被认为是有用且重要的，并且在世界各地的替代医疗实践中仍然具有重要意义。本研究的目的是评估和了解从喜马拉雅树状地衣 Ramalina roesleri 中分离出的乌苏里酸的抗菌潜力。乌苏里酸通过计算机模拟研究预测具有药物特性。通过与苯唑西林和头孢洛林比较的计算机相互作用分析，评估了乌苏里酸与青霉素结合蛋白-PBP2a 的结合效率，PBP2a 是导致金黄色葡萄球菌产生耐药性的蛋白质。此外，通过测定乌苏里酸对耐甲氧西林金黄色葡萄球菌（MRSA）临床分离株的抗菌潜力来验证计算机模拟建模的验证。共纳入 28 株从医院/医学生中收集的临床分离株进行研究，采用琼脂平板稀释法测定抗菌活性，随后进行时间杀伤动力学和协同研究。获得扫描电子显微镜（SEM）照片以显示乌苏里酸对 MRSA 的细胞壁破坏。对接结果清楚地表明，乌苏里酸（Glide XP G 评分：10.968；Glide 能量-64.869）与 PBP2a 的结合潜力增强，优于参考化合物苯唑西林（Glide XP G 评分：6.596；Glide 能量-53.285）的能量范围，与共晶配体头孢洛林大致相当（Glide XP G 评分：12.20；Glide 能量-70.322）。头孢洛林被认为比苯唑西林对 MRSA 更有效。乌苏里酸对 MRSA 临床分离株和参考菌株（NCTC-6571）的最小抑菌浓度（MIC）范围为 32-128μg/ml。乌苏里酸与 PBP2a 的高亲和力通过计算机模拟研究得到证明，这进一步通过乌苏里酸对 MRSA 临床分离株的显著抑制活性得到证实。
