Garcia-Marques Fernando J, Zakrasek Elissa, Bermudez Abel, Polasko Alexandra L, Liu Shiqin, Stoyanova Tanya, Brooks James D, Lavelle John, Pitteri Sharon J
Canary Center at Stanford for Cancer Early Detection, Department of Radiology, Stanford University School of Medicine Palo Alto, CA 94304, USA.
Veterans Affairs Palo Alto Health Care System Palo Alto, CA 94304, USA.
Am J Clin Exp Urol. 2023 Jun 15;11(3):206-219. eCollection 2023.
After spinal cord injury (SCI), use chronic urinary catheters for bladder management is common, making these patients especially vulnerable to catheter-associated complications. Chronic catheterization is associated with bacterial colonization and frequent catheter-associated urinary tract infections (CAUTI). One determinant of infection success and treatment resistance is production of catheter-associated biofilms, composed of microorganisms and host- and microbial-derived components. To better understand the biofilm microenvironment, we performed proteomics analysis of catheter-associated biofilms and paired urine samples from four people with SCI with chronic indwelling urinary catheters. We developed a novel method for the removal of adhered cellular components on catheters that contained both human and microbial homologous proteins. Proteins from seven microbial species were identified including: , and . Peptides identified from catheter biofilms were assigned to 4,820 unique proteins, with 61% of proteins assigned to the biofilm-associated microorganisms, while the remainder were human-derived. Contrastingly, in urine, only 51% were assigned to biofilm-associated microorganisms and 4,554 proteins were identified as a human-derived. Of the proteins assigned to microorganisms in the biofilm and paired urine, , and had greater associations with the biofilm phase, whereas and had greater associations with the urine phase, thus demonstrating a significant difference between the urine and adhered microbial communities. The microbial proteins that differed significantly between the biofilm and paired urine samples mapped to pathways associated with amino acid synthesis, likely related to adaptation to high urea concentrations in the urine, and growth and protein synthesis in bacteria in the biofilm. Human proteins demonstrated enrichment for immune response in the catheter-associated biofilm. Proteomic analysis of catheter-associated biofilms and paired urine samples has the potential to provide detailed information on host and bacterial responses to chronic indwelling urinary catheters and could be useful for understanding complications of chronic indwelling catheters including CAUTIs, urinary stones, and catheter blockages.
脊髓损伤（SCI）后，使用慢性导尿管进行膀胱管理很常见，这使得这些患者特别容易出现与导尿管相关的并发症。长期导尿与细菌定植和频繁的导尿管相关尿路感染（CAUTI）有关。感染成功和治疗耐药的一个决定因素是由微生物以及宿主和微生物衍生成分组成的导尿管相关生物膜的产生。为了更好地了解生物膜微环境，我们对四名患有慢性留置导尿管的脊髓损伤患者的导尿管相关生物膜和配对尿液样本进行了蛋白质组学分析。我们开发了一种新方法，用于去除导尿管上粘附的细胞成分，这些成分包含人类和微生物同源蛋白。鉴定出了七种微生物的蛋白质，包括： ，以及 。从导尿管生物膜中鉴定出的肽被分配到4820种独特的蛋白质中，其中61%的蛋白质被分配到生物膜相关微生物中，其余的是人类来源的。相比之下，在尿液中，只有51%被分配到生物膜相关微生物中，并且有4554种蛋白质被鉴定为人类来源的。在生物膜和配对尿液中分配给微生物的蛋白质中， 、 和 与生物膜阶段的关联更大，而 和 与尿液阶段的关联更大，从而证明尿液和粘附的微生物群落之间存在显著差异。生物膜和配对尿液样本之间差异显著的微生物蛋白质映射到与氨基酸合成相关的途径，这可能与适应尿液中的高尿素浓度以及生物膜中细菌的生长和蛋白质合成有关。人类蛋白质在导尿管相关生物膜中表现出免疫反应的富集。对导尿管相关生物膜和配对尿液样本进行蛋白质组学分析有可能提供关于宿主和细菌对慢性留置导尿管反应的详细信息，并且对于理解慢性留置导尿管的并发症（包括CAUTI、尿路结石和导尿管堵塞）可能有用。
