Laboratory for Cellulose & Wood Materials, Empa-Swiss Federal Laboratories for Materials Science and Technology, Überlandstrasse 129, 8600 Dübendorf, Switzerland.
Institute of Food Nutrition and Health, ETH Zurich, Schmelzbergstrasse 7, 8092 Zurich, Switzerland.
Biomacromolecules. 2021 Oct 11;22(10):4327-4336. doi: 10.1021/acs.biomac.1c00870. Epub 2021 Sep 17.
Antimicrobial resistance in microorganisms will cause millions of deaths and pose a vast burden on health systems; therefore, alternatives to existing small-molecule antibiotics have to be developed. Lysozyme is an antimicrobial enzyme and has broad-spectrum antimicrobial activity in different aggregated forms. Here, we propose a reductive pathway to obtain colloidally stable amyloid-like worm-shaped lysozyme nanoparticles (worms) from hen egg white lysozyme (HEWL) and compare them to amyloid fibrils made in an acid hydrolysis pathway. The aggregation of HEWL into worms follows strongly pH-dependent kinetics and induces a structural transition from α-helices to β-sheets. Both HEWL worms and amyloid fibrils show broad-spectrum antimicrobial activity against the bacteria (Gram-positive), (Gram-negative), and the fungus . The colloidal stability of the worms allows the determination of minimum inhibitory concentrations, which are lower than that for native HEWL in the case of . Overall, amyloid fibrils have the strongest antimicrobial effect, likely due to the increased positive charge compared to native HEWL. The structural and functional characterizations of HEWL worms and amyloids investigated herein are critical for understanding the detailed mechanisms of antimicrobial activity and opens up new avenues for the design of broad-spectrum antimicrobial materials for use in various applications.
微生物中的抗药性会导致数百万人死亡，并给卫生系统带来巨大负担；因此，必须开发现有的小分子抗生素的替代品。溶菌酶是一种抗菌酶，具有不同聚集形式的广谱抗菌活性。在这里，我们提出了一种还原途径，从鸡蛋白溶菌酶（HEWL）获得胶体稳定的类似淀粉样虫形溶菌酶纳米颗粒（蠕虫），并将其与在酸水解途径中制成的淀粉样纤维进行比较。HEWL 蠕虫的聚集遵循强烈依赖 pH 的动力学，并诱导从 α-螺旋到 β-折叠的结构转变。HEWL 蠕虫和淀粉样纤维都对细菌（革兰氏阳性菌）、（革兰氏阴性菌）和真菌表现出广谱的抗菌活性。蠕虫的胶体稳定性允许确定最小抑菌浓度，对于而言，其浓度比天然 HEWL 低。总的来说，淀粉样纤维具有最强的抗菌作用，这可能是由于与天然 HEWL 相比，其正电荷增加。本文对 HEWL 蠕虫和淀粉样纤维的结构和功能特性的研究对于理解抗菌活性的详细机制至关重要，并为设计用于各种应用的广谱抗菌材料开辟了新途径。
