A Metaproteomics Approach to Elucidate Host and Pathogen Protein Expression during Catheter-Associated Urinary Tract Infections (CAUTIs)
A Metaproteomics Approach to Elucidate Host and Pathogen Protein Expression during Catheter-Associated Urinary Tract Infections (CAUTIs)
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DOI：
10.1074/mcp.m114.043463
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发表时间：
2015-04-01
影响因子：
7
通讯作者：
Riedel, Katharina
中科院分区：
文献类型：
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作者：
Lassek, Christian;Burghartz, Melanie;Riedel, Katharina
长期置管不可避免地导致由多种细菌生物膜在导管上和导管内生长引起的导管相关性细菌尿。本研究的总体目标是：(1)揭示这种尿致病性生物膜的细菌群落结构和功能；(2)阐明尿中细菌毒力与人体免疫系统之间的相互作用。为此，采用宏蛋白质组学方法结合体外蛋白质组学分析来研究原和真核蛋白清单。我们的蛋白质组分析表明，所研究的导管的生物膜由三种细菌主导，即铜绿假单胞菌、摩根氏摩根杆菌和拟杆菌，并确定铁限制是膀胱环境中的主要挑战之一。对铜绿假单胞菌（P. aeruginosa）和摩根氏杆菌（M. moorganii）的体外蛋白质组学分析表明，这些条件致病菌能够通过产生铁载体和高表达相应受体来克服铁限制。值得注意的是，铜绿假单胞菌和摩根氏分枝杆菌的体内和体外蛋白质谱的比较也表明，细菌采用不同的策略来适应尿路。虽然铜绿假单胞菌似乎表达分泌和表面暴露的蛋白酶以逃避人类先天免疫系统并代谢氨基酸，但摩根氏分枝杆菌能够吸收糖并降解尿素。最有趣的是，对三名长期导尿患者和三名健康对照者的尿蛋白谱的比较表明，患者尿液中与中性粒细胞、巨噬细胞和补体系统相关的蛋白水平升高，这可能表明先天免疫系统对生物膜相关尿路感染的特异性激活。因此，我们假设导尿管相关性尿路感染通常无症状的性质可能是基于细菌毒力因子表达和人类免疫系统之间的微调平衡。
Long-term catheterization inevitably leads to a catheter-associated bacteriuria caused by multispecies bacterial biofilms growing on and in the catheters. The overall goal of the presented study was (1) to unravel bacterial community structure and function of such a uropathogenic biofilm and (2) to elucidate the interplay between bacterial virulence and the human immune system within the urine. To this end, a metaproteomics approach combined with in vitro proteomics analyses was employed to investigate both, the pro-and eukaryotic protein inventory. Our proteome analyses demonstrated that the biofilm of the investigated catheter is dominated by three bacterial species, that is, Pseudomonas aeruginosa, Morganella morganii, and Bacteroides sp., and identified iron limitation as one of the major challenges in the bladder environment. In vitro proteome analysis of P. aeruginosa and M. morganii isolated from the biofilm revealed that these opportunistic pathogens are able to overcome iron restriction via the production of siderophores and high expression of corresponding receptors. Notably, a comparison of in vivo and in vitro protein profiles of P. aeruginosa and M. morganii also indicated that the bacteria employ different strategies to adapt to the urinary tract. Although P. aeruginosa seems to express secreted and surface-exposed proteases to escape the human innate immune system and metabolizes amino acids, M. morganii is able to take up sugars and to degrade urea. Most interestingly, a comparison of urine protein profiles of three long-term catheterized patients and three healthy control persons demonstrated the elevated level of proteins associated with neutrophils, macrophages, and the complement system in the patient's urine, which might point to a specific activation of the innate immune system in response to biofilm-associated urinary tract infections. We thus hypothesize that the often asymptomatic nature of catheter-associated urinary tract infections might be based on a fine-tuned balance between the expression of bacterial virulence factors and the human immune system.