Schandl Stephan, Osondu-Chuka Goodness, Guagliano Giuseppe, Perak Stjepan, Petrini Paola, Briatico-Vangosa Francesco, Reimhult Erik, Guillaume Olivier
Institute of Materials Science and Technology, Technische Universität Wien, Vienna, Austria.
Austrian Cluster of Tissue Regeneration, Austria.
J Mater Chem B. 2025 Feb 19;13(8):2796-2809. doi: 10.1039/d4tb02675f.
The reason why certain bacteria, , (PA), produce acetylated alginate (Alg) in their biofilms remains one of the most intriguing facts in microbiology. Being the main structural component of the secreted biofilm, like the one formed in the lungs of cystic fibrosis (CF) patients, Alg plays a crucial role in protecting the bacteria from environmental stress and potential threats. Nonetheless, to investigate the PA biofilm environment and its lack of susceptibility to antibiotic treatment, the currently developed biofilm models use native seaweed Alg, which is a non-acetylated Alg. The role of the acetyl side group on the backbone of bacterial Alg has never been elucidated, and the transposition of experimental results obtained from such systems to clinical conditions (, to treat CF-infection) may be hazardous. We systematically investigated the influence of acetylation on the physico-chemical and mechanical properties of Alg in solution and Ca-crosslinked hydrogels. Furthermore, we assessed how the acetylation influenced the interaction of Alg with tobramycin, a common aminoglycoside antibiotic for PA. Our study revealed that the degree of acetylation directly impacts the viscosity and Young's Modulus of Alg in a pH-dependent manner. Acetylation increased the mesh size in biofilm-like Alg hydrogels, directly influencing antibiotic penetration. Our results provide essential insights to create more clinically relevant infection models to test the efficacy of new drugs or to better understand the 3D microenvironment of PA biofilms.
某些细菌，如铜绿假单胞菌（PA），在其生物膜中产生乙酰化藻酸盐（Alg）的原因仍是微生物学中最引人关注的事实之一。作为分泌型生物膜的主要结构成分，如在囊性纤维化（CF）患者肺部形成的生物膜，Alg在保护细菌免受环境压力和潜在威胁方面起着关键作用。尽管如此，为了研究PA生物膜环境及其对抗生素治疗的不敏感性，目前开发的生物膜模型使用的是天然海藻Alg，即非乙酰化Alg。细菌Alg主链上乙酰侧基的作用从未得到阐明，将从此类系统获得的实验结果转化到临床情况（如治疗CF感染）可能存在风险。我们系统地研究了乙酰化对溶液中Alg以及钙交联水凝胶的物理化学和力学性能的影响。此外，我们评估了乙酰化如何影响Alg与妥布霉素（一种用于PA的常见氨基糖苷类抗生素）的相互作用。我们的研究表明，乙酰化程度以pH依赖的方式直接影响Alg的粘度和杨氏模量。乙酰化增加了生物膜样Alg水凝胶中的网孔尺寸，直接影响抗生素的渗透。我们的结果为创建更具临床相关性的感染模型以测试新药疗效或更好地理解PA生物膜的三维微环境提供了重要见解。
