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输尿管支架管存在复杂生物膜,具有丰富的微生物群-代谢物相互作用。

Ureteral Stents Harbor Complex Biofilms With Rich Microbiome-Metabolite Interactions.

作者信息

Werneburg Glenn T, Hettel Daniel, Lundy Scott D, Adler Ava, De Smita, Mukherjee Sromona D, Rackley Raymond R, Shoskes Daniel A, Miller Aaron W

机构信息

Department of Urology, Glickman Urological and Kidney Institute, 9500 Euclid Ave, Cleveland Clinic Foundation, Cleveland, Ohio.

出版信息

J Urol. 2023 May;209(5):950-962. doi: 10.1097/JU.0000000000003200. Epub 2023 Feb 1.

Abstract

PURPOSE

We sought to determine microbe-metabolite composition and interactions within indwelling ureteral stent biofilms, determine their association with patient factors including infection, and reconstitute biofilm formation on relevant surface materials in vitro.

MATERIALS AND METHODS

Upon ureteral stent removal from patients, proximal and distal ends were swabbed. Samples were analyzed by 16S next-generation sequencing and metabolomics. A continuous-flow stir-tank bioreactor was used to reconstitute and quantify in vitro biofilm formation from stent-isolated bacteria on stent-related materials including silicone, polytetrafluoroethylene, polyurethane, polycarbonate, and titanium. Diversity, relative abundance, and association with clinical factors were analyzed with ANOVA and Bonferroni -tests or PERMANOVA. Biofilm deposition by microbial strain and device material type were analyzed using plate counts and scanning electron microscopy following bioreactor incubation.

RESULTS

All 73 samples from 37 ureteral stents harbored microbiota. Specific genera were more abundant in samples from stents wherein there was antibiotic exposure during indwelling time (, ) and in those associated with infection (, ). The enriched interaction subnetwork in stent-associated infection included and metabolite 9-methyl-7-bromoeudistomin. Strains identified as clinically relevant and central to interaction networks all reconstituted biofilm in vitro, with differential formation by strain ( most) and material type (titanium least).

CONCLUSIONS

Ureteral stent biofilms exhibit patterns unique to stent-associated infection and antibiotic exposure during indwelling time. Microbes isolated from stents reconstituted biofilm formation in vitro. This work provides a platform to test novel materials, evaluate new coatings for anti-biofilm properties, and explore commensal strain use for bacterial interference against pathogens.

摘要

目的

我们试图确定留置输尿管支架生物膜内的微生物-代谢物组成及相互作用,确定它们与包括感染在内的患者因素之间的关联,并在体外相关表面材料上重建生物膜形成过程。

材料与方法

从患者体内取出输尿管支架后,对其近端和远端进行擦拭取样。样本通过16S下一代测序和代谢组学进行分析。使用连续流搅拌罐式生物反应器在包括硅胶、聚四氟乙烯、聚氨酯、聚碳酸酯和钛在内的与支架相关的材料上,从支架分离出的细菌重建并定量体外生物膜形成。使用方差分析和邦费罗尼检验或PERMANOVA分析多样性、相对丰度以及与临床因素的关联。在生物反应器孵育后,使用平板计数和扫描电子显微镜分析微生物菌株和装置材料类型对生物膜沉积的影响。

结果

来自37个输尿管支架的所有73个样本都含有微生物群。在留置期间有抗生素暴露的支架样本(,)以及与感染相关的支架样本(,)中,特定菌属更为丰富。支架相关感染中富集的相互作用子网包括和代谢物9-甲基-7-溴优地斯明。被鉴定为临床相关且对相互作用网络至关重要的菌株均在体外重建了生物膜,不同菌株(大多数)和材料类型(钛最少)的生物膜形成存在差异。

结论

输尿管支架生物膜表现出与支架相关感染以及留置期间抗生素暴露相关的独特模式。从支架分离出的微生物在体外重建了生物膜形成过程。这项工作提供了一个平台,用于测试新型材料、评估抗生物膜特性的新涂层,并探索利用共生菌株对病原体进行细菌干扰。

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