Inhibiting host-protein deposition on urinary catheters reduces associated urinary tract infections.
Inhibiting host-protein deposition on urinary catheters reduces associated urinary tract infections.
复制标题
抑制尿管上的宿主蛋白沉积可减少相关的尿路感染。
DOI：
10.7554/elife.75798
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发表时间：
2022-03-29
期刊：
影响因子：
7.7
通讯作者：
Flores-Mireles AL
中科院分区：
文献类型：
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作者：
Andersen MJ;Fong C;La Bella AA;Molina JJ;Molesan A;Champion MM;Howell C;Flores-Mireles AL
微生物粘附在医疗器械上是医院获得性感染的常见原因，尤其是导尿管。如果治疗不当，这些感染会导致并发症并加剧抗菌素耐药性。导尿管的使用加剧了膀胱炎症，释放宿主血清蛋白，包括纤维蛋白原（Fg），进入膀胱，存款在导尿管上。粪肠球菌使用Fg作为支架结合并持续存在于膀胱中，尽管进行了抗生素治疗。Fg-病原体相互作用的抑制显著减少感染。在这里，我们表明沉积的Fg对尿路病原体E是有利的。粪肠球菌、大肠杆菌、铜绿假单胞菌、克雷伯氏菌。pneumoniae、A. baumannii和C.白念珠菌，表明靶向导管蛋白沉积可以减少定植，从而为导管相关性尿路感染（CTTI）提供有效的干预措施。在一个小鼠模型中，宿主蛋白质沉积减少，使用液体注入硅胶导管，导致导管上的定植减少，膀胱中，体内传播。此外，蛋白质组学揭示了显著减少沉积的主机分泌的蛋白质的液体注入导管表面。我们的研究结果表明，靶向微生物结合支架可能是一种有效的预防尿路感染和其他医疗器械感染的干预措施。
Microbial adhesion to medical devices is common for hospital-acquired infections, particularly for urinary catheters. If not properly treated these infections cause complications and exacerbate antimicrobial resistance. Catheter use elicits bladder inflammation, releasing host serum proteins, including fibrinogen (Fg), into the bladder, which deposit on the urinary catheter. Enterococcus faecalis uses Fg as a scaffold to bind and persist in the bladder despite antibiotic treatments. Inhibition of Fg–pathogen interaction significantly reduces infection. Here, we show deposited Fg is advantageous for uropathogens E. faecalis, Escherichia coli, Pseudomonas aeruginosa, K. pneumoniae, A. baumannii, and C. albicans, suggesting that targeting catheter protein deposition may reduce colonization creating an effective intervention for catheter-associated urinary tract infections (CAUTIs). In a mouse model of CAUTI, host-protein deposition was reduced, using liquid-infused silicone catheters, resulting in decreased colonization on catheters, in bladders, and dissemination in vivo. Furthermore, proteomics revealed a significant decrease in deposition of host-secreted proteins on liquid-infused catheter surfaces. Our findings suggest targeting microbial-binding scaffolds may be an effective antibiotic-sparing intervention for use against CAUTIs and other medical device infections.