Piktel Ewelina, Wnorowska Urszula, Depciuch Joanna, Łysik Dawid, Cieśluk Mateusz, Fiedoruk Krzysztof, Mystkowska Joanna, Parlińska-Wojtan Magdalena, Janmey Paul A, Bucki Robert
Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Białystok, Białystok, 15-222, Poland.
Institute of Nuclear Physic, Polish Academy of Sciences, Krakow, PL-31342, Poland.
Infect Drug Resist. 2022 Mar 5;15:851-871. doi: 10.2147/IDR.S348357. eCollection 2022.
Extracellular polymeric substances (EPS) produced by bacteria, as they form a biofilm, determine the stability and viscoelastic properties of biofilms and prevent antibiotics from penetrating this multicellular structure. To date, studies demonstrated that an appropriate optimization of the chemistry and morphology of nanotherapeutics might provide a favorable approach to control their interaction with EPS and/or diffusion within the biofilm matrix. Targeting the biofilms' EPS, which in certain conditions can adopt liquid crystal structure, was demonstrated to improve the anti-biofilm activity of antibiotics and nanoparticles. A similar effect is achievable by interfering EPS' production by mucoactive agents, such as N-acetyl-cysteine (NAC). In our previous study, we demonstrated the nanogram efficiency of non-spherical gold nanoparticles, which due to their physicochemical features, particularly morphology, were noted to be superior in antimicrobial activity compared to their spherical-shaped counterparts.
To explore the importance of EPS matrix modulation in achieving a suitable efficiency of peanut-shaped gold nanoparticles (AuP NPs) against biofilms produced by strains isolated from cystic fibrosis patients, fluorescence microscopy, as well as resazurin staining were employed. Rheological parameters of AuP NPs-treated biofilms were investigated by rotational and creep-recovery tests using a rheometer in a plate-plate arrangement.
We demonstrated that tested nanoparticles significantly inhibit the growth of mono- and mixed-species biofilms, particularly when combined with NAC. Notably, gold nanopeanuts were shown to decrease the viscosity and increase the creep compliance of biofilm, similarly to EPS-targeting NAC. Synergistic activity of AuP NPs with tobramycin was also observed, and the AuP NPs were able to eradicate bacteria within biofilms formed by tobramycin-resistant isolates.
We propose that peanut-shaped gold nanoparticles should be considered as a potent therapeutic agent against biofilms.
细菌产生的细胞外聚合物（EPS）在形成生物膜时，决定了生物膜的稳定性和粘弹性，并阻止抗生素穿透这种多细胞结构。迄今为止，研究表明，对纳米治疗剂的化学性质和形态进行适当优化，可能为控制其与EPS的相互作用和/或在生物膜基质中的扩散提供一种有利的方法。已证明靶向生物膜的EPS（在某些条件下可呈现液晶结构）可提高抗生素和纳米颗粒的抗生物膜活性。通过粘液活性剂（如N-乙酰半胱氨酸（NAC））干扰EPS的产生也可达到类似效果。在我们之前的研究中，我们证明了非球形金纳米颗粒的纳克效率，由于其物理化学特性，特别是形态，其抗菌活性优于球形对应物。
为了探究EPS基质调节在实现花生形金纳米颗粒（AuP NPs）对从囊性纤维化患者分离出的菌株产生的生物膜具有合适效率方面的重要性，采用了荧光显微镜以及刃天青染色法。使用流变仪以平板-平板配置通过旋转和蠕变-恢复测试研究了AuP NPs处理的生物膜的流变学参数。
我们证明，测试的纳米颗粒显著抑制单物种和混合物种生物膜的生长，特别是与NAC联合使用时。值得注意的是，金纳米花生显示出可降低生物膜的粘度并增加其蠕变柔量，类似于靶向EPS的NAC。还观察到AuP NPs与妥布霉素的协同活性，并且AuP NPs能够根除由耐妥布霉素分离株形成的生物膜内的细菌。
我们建议花生形金纳米颗粒应被视为一种有效的抗生物膜治疗剂。
