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纳米氧化锌转运土霉素 - 锌络合物[ZnOTc]对耐土霉素嗜水气单胞菌的抗菌特性及计算机模拟研究

Antibacterial properties and in silico modeling perspective of nano ZnO transported oxytetracycline-Zn complex [ZnOTc] against oxytetracycline-resistant Aeromonas hydrophila.

作者信息

Sarkar Dhruba Jyoti, Mohanty Debasmita, Raut Subhashree Subhasmita, Kumar Das Basanta

机构信息

Aquatic Environmental Biotechnology and Nanotechnology Division, ICAR-Central Inland Fisheries Research Institute, Barrackpore, Kolkata, 700120, India.

Riverine and Estuarine Fisheries Division, ICAR-Central Inland Fisheries Research Institute, Barrackpore, Kolkata, 700120, India.

出版信息

J Antibiot (Tokyo). 2022 Nov;75(11):635-649. doi: 10.1038/s41429-022-00564-0. Epub 2022 Sep 20.

Abstract

Emergence of antibiotics resistance has threatening consequences not only for human health but also for animal health issues in agriculture. Several animal pathogenic bacteria have developed antibiotic resistance and managing same has tremendous cost repercussions and may lead to total harvest loss. Hence in the present study, efforts are made to revitalize an old antibiotic molecule, oxytetracycline (OTc), through nanodelivery approaches using zinc oxide nanoparticles (nZnO) to confront OTc resistant fish pathogenic bacteria Aeromonas hydrophila. OTc was impregnated in nZnO through in situ precipitation method to develop OTc loaded ZnO nanoparticles (OTc@nZnO) with average size of 99.42 nm. Spectroscopic investigation of same revealed complexation of Zn with amide and aromatic carbonyl moieties of OTc [ZnOTc]. The complex performed better against A. hydrophila with 7-15 mm inhibition zone as compared to nil for bare OTc at same dose. OTc also showed MIC of 150 µg ml and for OTc@nZnO it was 7.02 µg ml with faster killing rate (k, -0.95). In silico docking simulation suggest that [ZnOTc] had low binding affinity (LBE > -5.00 kcal mol) toward TetR(E) and TetA(E) proteins of A. hydrophila as compared to OTc (LBE < -8.00 kcal mol). This study postulates that [ZnOTc] released from OTc@nZnO can escape TetR(E) and TetA(E) resistance proteins and bind at 30S ribosomal subunit with high affinity (<-11.00 kcal mol) to exert antibacterial properties. In the recent scenario of recurrent antimicrobial resistance, the develop antibiotic-nanocomposites could come out as potential solution, however further study is required for its feasibility for use in animal health care.

摘要

抗生素耐药性的出现不仅对人类健康构成威胁,也对农业中的动物健康问题产生影响。几种动物病原菌已产生抗生素耐药性,应对这一问题成本高昂,甚至可能导致绝收。因此,在本研究中,我们尝试通过使用氧化锌纳米颗粒(nZnO)的纳米递送方法来重振一种古老的抗生素分子——土霉素(OTc),以对抗对OTc耐药的鱼类病原菌嗜水气单胞菌。通过原位沉淀法将OTc负载于nZnO中,制备出平均粒径为99.42 nm的负载OTc的ZnO纳米颗粒(OTc@nZnO)。光谱研究表明,Zn与OTc的酰胺和芳香羰基部分形成了络合物[ZnOTc]。与相同剂量下无抑菌圈的纯OTc相比,该络合物对嗜水气单胞菌的抑菌圈为7 - 15 mm,表现更佳。OTc的最低抑菌浓度(MIC)为150 μg/ml,而OTc@nZnO的MIC为7.02 μg/ml,且杀菌速率更快(k,-0.95)。计算机对接模拟表明,与OTc(结合自由能LBE < -8.00 kcal/mol)相比,[ZnOTc]对嗜水气单胞菌的TetR(E)和TetA(E)蛋白的结合亲和力较低(LBE > -5.00 kcal/mol)。本研究推测,OTc@nZnO释放的[ZnOTc]能够避开TetR(E)和TetA(E)耐药蛋白,并以高亲和力(< -11.00 kcal/mol)结合到30S核糖体亚基上发挥抗菌作用。在当前抗菌耐药性不断反复的情况下,开发的抗生素 - 纳米复合材料可能成为潜在的解决方案,然而其在动物保健中的应用可行性还需要进一步研究。

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