Recent evidence indicates that microbial biofilm aggregates inhabit the lungs of COPD patients and actively contribute towards chronic colonization and repeat infections. However, there are no contextually relevant complex biofilm models for COPD research. In this study, a meta-analysis of the lung microbiome in COPD was used to inform development of an optimized biofilm model composed of genera highly associated with COPD. Bioinformatic analysis showed that although diversity matrices of COPD microbiomes were similar to healthy controls, and internal compositions made it possible to accurately differentiate between these cohorts (AUC = 0.939). Genera that best defined these patients included Haemophilus, Moraxella and Streptococcus. Many studies fail to account for fungi; therefore, Candida albicans was included in the creation of an interkingdom biofilm model. These organisms formed a biofilm capable of tolerating high concentrations of antimicrobial therapies with no significant reductions in viability. However, combined therapies of antibiotics and an antifungal resulted in significant reductions in viable cells throughout the biofilm (p < 0.05). This biofilm model is representative of the COPD lung microbiome and results from in vitro antimicrobial challenge experiments indicate that targeting both bacteria and fungi in these interkingdom communities will be required for more positive clinical outcomes.

中文翻译：

---

慢性阻塞性肺疾病多物种生物膜的知情开发

最近的证据表明，微生物生物膜聚集在慢性阻塞性肺病患者的肺部，并积极促进慢性定植和重复感染。然而，慢性阻塞性肺病研究没有上下文相关的复杂生物膜模型。在这项研究中，对慢性阻塞性肺病肺微生物组的荟萃分析被用来为开发由与慢性阻塞性肺病高度相关的菌属组成的优化生物膜模型提供信息。生物信息学分析表明，尽管 COPD 微生物群的多样性矩阵与健康对照相似，但内部组成使得准确区分这些群体成为可能 (AUC = 0.939)。最能定义这些患者的属包括嗜血杆菌属、莫拉氏菌属和链球菌属。许多研究未能解释真菌；因此，白色念珠菌被纳入界间生物膜模型的创建中。这些生物体形成了能够耐受高浓度抗菌疗法的生物膜，且存活率没有显着降低。然而，抗生素和抗真菌药物的联合治疗导致整个生物膜中活细胞的显着减少（p < 0.05）。该生物膜模型代表了慢性阻塞性肺病肺微生物组，体外抗菌挑战实验的结果表明，需要针对这些跨界群落中的细菌和真菌，才能获得更积极的临床结果。