Department of Biotechnology & Bioinformatics, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh, 173234, India.
Department of Biotechnology & Bioinformatics, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh, 173234, India.
Biochem Biophys Res Commun. 2022 Dec 25;636(Pt 2):10-17. doi: 10.1016/j.bbrc.2022.10.095. Epub 2022 Oct 31.
Acinetobacter baumannii forms robust biofilms, which aid protection against antimicrobials and account for adaptation in hospital settings. Biofilm formation by A. baumannii has worsens the scenario of drug resistance. Therefore, new strategies are required to tackle biofilm-forming multidrug-resistant A. baumannii. The present study investigated compounds with antimicrobials and antibiofilm properties against A. baumannii. Different antimicrobials were selected from available reports. Initially, comparative antimicrobial activity against A. baumannii isolates was assessed. Most potent antimicrobial compounds were further analyzed for time-kill kinetics, biofilm inhibition, and exopolysaccharide (EPS) reduction in their presence and absence. The antibiofilm potentials were also confirmed with SEM analysis. The relative gene expression of the csuE gene and molecular docking was carried out to investigate the molecular mechanism of mature biofilm disruption. The results demonstrated eugenol and geraniol as the most potent inhibitors with MICs of 6.08 mM and 3.24 mM, respectively, with the potential to significantly inhibit growth and EPS production. Complete inhibition of A. baumannii mature biofilms was observed with a maximum of 60.89 mM and 129.6 mM concentrations of eugenol and geraniol, respectively. The SEM analysis and lower expression of the csuE gene showed the effectiveness of potent antibiofilm agents. In-silico docking showed efficient binding of eugenol and geraniol with the csuE protein of archaic pilus. The findings of molecular docking concordant the assumption that these molecules may prevent the assembly of mature pilus, which results in abolished biofilms. In conclusion, the antibiofilm virtues of eugenol and geraniol were elucidated to be used in the future to control the persistence of biofilm-forming drug-resistant A. baumannii.
鲍曼不动杆菌形成坚固的生物膜，有助于抵御抗菌药物，并适应医院环境。鲍曼不动杆菌的生物膜形成使耐药情况恶化。因此，需要新的策略来解决形成生物膜的多药耐药鲍曼不动杆菌。本研究调查了具有抗菌和抗生物膜特性的化合物对鲍曼不动杆菌的作用。从现有报道中选择了不同的抗菌药物。首先，评估了它们对鲍曼不动杆菌分离株的比较抗菌活性。进一步分析了最有效的抗菌化合物的时间杀伤动力学、生物膜抑制作用以及在存在和不存在它们的情况下胞外多糖（EPS）的减少。还用 SEM 分析证实了抗生物膜潜能。进行相对 csuE 基因表达和分子对接，以研究成熟生物膜破坏的分子机制。结果表明，丁香酚和香叶醇是最有效的抑制剂，MIC 分别为 6.08mM 和 3.24mM，具有显著抑制生长和 EPS 产生的潜力。用丁香酚和香叶醇的最大浓度 60.89mM 和 129.6mM 观察到对鲍曼不动杆菌成熟生物膜的完全抑制。SEM 分析和 csuE 基因的低表达表明了有效抗生物膜剂的有效性。分子对接表明丁香酚和香叶醇与古菌菌毛的 csuE 蛋白具有有效的结合。分子对接的结果与假设一致，即这些分子可能阻止成熟菌毛的组装，从而导致生物膜的消失。总之，阐明了丁香酚和香叶醇的抗生物膜特性，将来可用于控制形成生物膜的多药耐药鲍曼不动杆菌的持久性。
