脊髓损伤患者尿液和导管相关生物膜的蛋白质组学分析。

IF 1.5 Q3 UROLOGY & NEPHROLOGY
American journal of clinical and experimental urology Pub Date : 2023-06-15 eCollection Date: 2023-01-01
Fernando J Garcia-Marques, Elissa Zakrasek, Abel Bermudez, Alexandra L Polasko, Shiqin Liu, Tanya Stoyanova, James D Brooks, John Lavelle, Sharon J Pitteri
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引用次数: 0

摘要

脊髓损伤(SCI)后,使用慢性导尿管管理膀胱很常见,因此这些患者特别容易出现导尿管相关并发症。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。感染成功率和耐药性的一个决定因素是导管相关生物膜的产生,生物膜由微生物和宿主及微生物衍生成分组成。为了更好地了解生物膜的微环境,我们对导管相关生物膜和配对尿样进行了蛋白质组学分析,配对尿样来自四名长期留置导尿管的 SCI 患者。我们开发了一种新方法,用于清除导尿管上的粘附细胞成分,其中包含人类和微生物的同源蛋白。我们鉴定了来自七种微生物的蛋白质,包括从导管生物膜中鉴定出的肽被归类为 4820 种独特的蛋白质,其中 61% 的蛋白质被归类为生物膜相关微生物的蛋白质,而其余的蛋白质则来自人类。相反,在尿液中,只有 51% 的蛋白质被分配给生物膜相关微生物,4554 个蛋白质被鉴定为源自人类。在分配给生物膜和配对尿液中微生物的蛋白质中,肠球菌、念珠菌属和奇异变形杆菌与生物膜阶段的关联度更高,而大肠杆菌和克雷伯氏菌与尿液阶段的关联度更高,从而表明尿液和附着微生物群落之间存在显著差异。在生物膜样本和配对尿液样本之间存在显著差异的微生物蛋白质映射到与氨基酸合成相关的通路,这可能与适应尿液中的高浓度尿素以及生物膜中细菌的生长和蛋白质合成有关。导管相关生物膜中的人类蛋白质富集了免疫反应。对导尿管相关生物膜和配对尿液样本进行蛋白质组分析,有可能提供宿主和细菌对慢性留置导尿管反应的详细信息,有助于了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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Proteomics analysis of urine and catheter-associated biofilms in spinal cord injury patients.

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: Escherichia coli, Klebsiella species (spp), Enterococcus spp, Proteus mirabilis, Pseudomonas spp, Staphylococcus spp, and Candida spp. 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, Enterococcus, Candida spp, and P. mirabilis had greater associations with the biofilm phase, whereas E. coli and Klebsiella 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.

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