Bioinformatics Research Laboratory, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, India.
Microbial Diversity Research Centre, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, India.
Comput Biol Chem. 2023 Jun;104:107829. doi: 10.1016/j.compbiolchem.2023.107829. Epub 2023 Feb 15.
The rapid development of multi-drug resistant (MDR) pathogens adds urgency to search for novel and safe drugs having promising action on new and re-emerging infectious pathogens. Serratia marcescens is an MDR pathogen that causes several-healthcare associated infections. Curbing bacterial virulence, rather than inhibiting its growth, is a promising strategy to diminish the pathogenesis of infectious bacteria, reduce the development of antimicrobial resistance, and boost the host immune power to eradicate infections. Bergamot essential oil (BEO) is a remarkable source of promising therapeutics against pathogens. Therefore, the present investigation aimed to analyze the major phytocompounds from BEO against S. marcescens virulent proteins using in silico studies. The analysis of BEO phytocompounds was achieved by Gas chromatography-mass spectrometry (GC-MS) method. The molecular docking was carried out using the SP and XP docking protocol of the Glide program. The drug-likeness and pharmacokinetics properties (ADMET properties) were analyzed with SwissADME and pkCSM server. The results revealed that the major compounds present in BEO are Linalool (8.17%), D-Limonene (21.26%), and Linalyl acetate (26.91%). Molecular docking analysis revealed that these compounds docked strongly within the binding cavities of Serratia protease and FabI model which in turn curb the pathogenesis of this bacteria. Linalool interacted with the Serratia protease and FabI with a binding energy of - 3.130 kcal/mol and - 3.939 kcal/mol, respectively. Based on the pharmacokinetics findings all lead BEO phytocompounds appear to be promising drug candidates. Overall, these results represent a significant step in the development of plant-based compounds as a promising inhibitor of the virulent proteins of the MDR S. marcescens.
多药耐药（MDR）病原体的迅速发展使得寻找对新出现和重新出现的传染病原体具有潜在作用的新型安全药物变得尤为紧迫。粘质沙雷氏菌是一种引起多种医疗相关感染的 MDR 病原体。抑制细菌毒力而不是抑制其生长是减少传染病细菌发病机制、减少抗菌药物耐药性发展和增强宿主免疫力以消除感染的有前途的策略。香柠檬精油（BEO）是一种针对病原体的有前途的治疗方法的重要来源。因此，本研究旨在使用计算机模拟研究分析 BEO 中的主要植物化合物对粘质沙雷氏菌毒力蛋白的作用。BEO 植物化合物的分析通过气相色谱-质谱联用（GC-MS）方法实现。分子对接使用 Glide 程序的 SP 和 XP 对接方案进行。药物相似性和药代动力学特性（ADMET 特性）使用 SwissADME 和 pkCSM 服务器进行分析。结果表明，BEO 中的主要化合物为芳樟醇（8.17%）、D-柠檬烯（21.26%）和乙酸芳樟酯（26.91%）。分子对接分析表明，这些化合物强烈结合在粘质沙雷氏菌蛋白酶和 FabI 模型的结合腔内，从而抑制了这种细菌的发病机制。芳樟醇与粘质沙雷氏菌蛋白酶和 FabI 的结合能分别为-3.130 kcal/mol 和-3.939 kcal/mol。基于药代动力学研究结果，所有 BEO 植物化合物都显示出成为有前途的药物候选物的潜力。总体而言，这些结果代表了植物化合物作为 MDR 粘质沙雷氏菌毒力蛋白潜在抑制剂的开发的重要一步。
