Grayton Quincy E, Nguyen Huan K, Broberg Christopher A, Ocampo Jeffrey, Nagy Sarah G, Schoenfisch Mark H
ACS Infect Dis. 2023 Sep 8;9(9):1730-1741. doi: 10.1021/acsinfecdis.3c00198. Epub 2023 Aug 11.
Compared to planktonic bacteria, biofilms are notoriously difficult to eradicate due to their inherent protection against the immune response and antimicrobial agents. Inducing biofilm dispersal to improve susceptibility to antibiotics is an attractive therapeutic avenue for eradicating biofilms. Nitric oxide (NO), an endogenous antibacterial agent, has previously been shown to induce biofilm dispersal, but with limited understanding of the effects of NO-release properties. Herein, the antibiofilm effects of five promising NO-releasing biopolymer candidates were studied by assessing dispersal, changes in biofilm viscoelasticity, and increased sensitization to tobramycin after treatment with NO. A threshold level of NO was needed to achieve biofilm dispersal, with longer-releasing systems requiring lower concentrations. The most positively charged NO-release systems (from the presence of primary amines) led to the greatest reduction in viscoelasticity of biofilms. Co-treatment of tobramycin with the NO-releasing biopolymer greatly decreased the dose of tobramycin required to eradicate tobramycin-susceptible and -resistant biofilms in both cellular and tissue models.
与浮游细菌相比，生物膜因其对免疫反应和抗菌剂具有固有的保护作用，故而极难根除。诱导生物膜分散以提高对抗生素的敏感性，是根除生物膜的一条颇具吸引力的治疗途径。一氧化氮（NO）作为一种内源性抗菌剂，此前已被证明可诱导生物膜分散，但对NO释放特性的影响了解有限。在此，通过评估生物膜分散、生物膜粘弹性变化以及用NO处理后对妥布霉素敏感性的增加，研究了五种有前景的释放NO的生物聚合物候选物的抗生物膜作用。实现生物膜分散需要一个NO阈值水平，释放时间较长的系统所需浓度较低。带正电荷最多的NO释放系统（由于伯胺的存在）导致生物膜的粘弹性降低幅度最大。在细胞和组织模型中，将妥布霉素与释放NO的生物聚合物联合处理，大大降低了根除对妥布霉素敏感和耐药生物膜所需的妥布霉素剂量。
