Synergistic Antibacterial Effect of ZnO Nanoparticles and Antibiotics against Multidrug-Resistant Biofilm Bacteria.

Majed M Masadeh, Noor M Bany-Ali, Mai S Khanfar, Karem H Alzoubi, Majd M Massadeh, Enaam M Almomani
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Abstract

Background: The misuse of antibiotics leads to a global increase in antibiotic resistance. Therefore, it is imperative to search for alternative compounds to conventional antibiotics. ZnO nanoparticles (Zn NP) are one of these alternatives because they are an effective option to overcome biofilm bacterial cells and a novel way to overcome multidrug resistance in bacteria. The current research study aims to characterize the efficacy of ZnO nanoparticles alone and in combination with other antibacterial drugs against bacterial biofilms.

Methods: ZnO NPs were prepared by co-precipitation method, and their anti-biofilm and antibacterial activities alone or combined with four types of broad-spectrum antibacterial (Norfloxacin, Colistin, Doxycycline, and Ampicillin) were evaluated against E. coli and S. aureus bacterial strains. Finally, the cytotoxicity and the hemolytic activity were evaluated.

Results: ZnO NPs were prepared, and results showed that their size was around 10 nm with a spherical shape and a zeta potential of -21.9. In addition, ZnO NPs were found to have a strong antibacterial effect against Gram-positive and Gram-negative microorganisms, with a minimum inhibitory concentration (MIC) of 62.5 and 125 μg/mL, respectively. Additionally, they could eradicate biofilmforming microorganisms at a concentration of 125 μg/m. ZnO NPs were found to be non-toxic to erythrocyte cells. Still, some toxicity was observed for Vero cells at effective concentration ranges needed to inhibit bacterial growth and eradicate biofilm-forming organisms. When combined with different antibacterial, ZnO NP demonstrated synergistic and additive effects with colistin, and the MIC and MBEC of the combination decreased significantly to 0.976 μg/mL against planktonic and biofilm strains of MDR Gram-positive bacteria, resulting in significantly reduced toxicity.

Conclusion: The findings of this study encourage the development of alternative therapies with high efficacy and low toxicity. ZnO nanoparticles have demonstrated promising results in overcoming multi-drug resistant bacteria and biofilms, and their combination with colistin has shown a significant reduction in toxicity. Further studies are needed to investigate the potential of ZnO nanoparticles as a viable alternative to conventional antibiotics.

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氧化锌纳米颗粒与抗生素对耐多药生物膜细菌的协同抗菌效果
背景:抗生素的滥用导致全球抗生素耐药性的增加。因此,寻找传统抗生素的替代化合物势在必行。氧化锌纳米粒子(Zn NP)是这些替代品之一,因为它们是克服生物膜细菌细胞的有效选择,也是克服细菌多重耐药性的一种新方法。目前的研究旨在确定氧化锌纳米粒子单独使用或与其他抗菌药物联合使用对细菌生物膜的疗效:方法:采用共沉淀法制备 ZnO NPs,并评估其单独或与四种广谱抗菌药物(诺氟沙星、可乐定、强力霉素和氨苄西林)联合使用对大肠杆菌和金黄色葡萄球菌的抗生物膜和抗菌活性。最后,还评估了细胞毒性和溶血活性:结果:制备出的 ZnO NPs 大小约为 10 nm,呈球形,Zeta 电位为 -21.9。此外,研究还发现 ZnO NPs 对革兰氏阳性和革兰氏阴性微生物具有很强的抗菌作用,其最低抑菌浓度(MIC)分别为 62.5 和 125 μg/mL。此外,在 125 μg/m 浓度下,它们还能消灭形成生物膜的微生物。研究发现,氧化锌纳米粒子对红细胞无毒。不过,在抑制细菌生长和根除生物膜形成微生物所需的有效浓度范围内,观察到氧化锌纳米粒子对 Vero 细胞有一定毒性。当氧化锌氮氧化物与不同的抗菌剂结合使用时,它与可乐定产生了协同和相加效应,对革兰氏阳性耐药菌的浮游菌株和生物膜菌株的 MIC 和 MBEC 显著下降至 0.976 μg/mL,从而大大降低了毒性:结论:本研究的发现有助于开发高效低毒的替代疗法。氧化锌纳米粒子在克服多重耐药细菌和生物膜方面取得了可喜的成果,其与可乐定的结合也显示出毒性的显著降低。需要进一步研究氧化锌纳米粒子作为传统抗生素可行替代品的潜力。
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