Andersen Marissa Jeme, Fong ChunKi, La Bella Alyssa Ann, Molina Jonathan Jesus, Molesan Alex, Champion Matthew M, Howell Caitlin, Flores-Mireles Ana L
Department of Biological Sciences, College of Science, University of Notre Dame, Notre Dame, United States.
Department of Chemical and Biomedical Engineering, College of Engineering, University of Maine, Orono, United States.
Elife. 2022 Mar 29;11:e75798. doi: 10.7554/eLife.75798.
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. 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 , , , , , and , 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.
微生物附着于医疗设备是医院获得性感染的常见原因，尤其是对于导尿管而言。如果这些感染得不到妥善治疗，就会引发并发症并加剧抗菌药物耐药性。使用导尿管会引发膀胱炎症，将包括纤维蛋白原（Fg）在内的宿主血清蛋白释放到膀胱中，这些蛋白会沉积在导尿管上。[某种微生物]利用Fg作为支架来结合并在膀胱中持续存在，即便接受了抗生素治疗也是如此。抑制Fg与病原体的相互作用可显著减少感染。在此，我们表明沉积的Fg对尿路病原体[列举的多种病原体名称]有利，这表明针对导尿管上蛋白质沉积进行干预可能会减少细菌定植，从而为导尿管相关尿路感染（CAUTIs）创造一种有效的干预措施。在CAUTI小鼠模型中，使用液体灌注硅胶导尿管可减少宿主蛋白沉积，从而减少导尿管上、膀胱中的细菌定植以及体内的细菌播散。此外，蛋白质组学显示宿主分泌蛋白在液体灌注导尿管表面的沉积显著减少。我们的研究结果表明，针对微生物结合支架进行干预可能是一种有效的减少抗生素使用的措施，可用于对抗CAUTIs和其他医疗设备感染。
