Durable fluid-like surface for sustainable biofilm inhibition

导管相关性尿路感染(CAUTIs)占急诊医院感染的30%以上。 细菌病原体最初在导尿管上定植并形成生物膜，然后侵入膀胱并最终 上尿路。长时间导尿(~30天)可使CAUTI100%发生。 为有症状的CAUTI开出的抗生素往往无法杀灭生物膜内的细菌。因此， 抑制生物被膜的形成将显著减少CAUTIs的机会。导尿管生物膜通常 具有混合细菌群落的多菌剂。耐用的生物表面涂层将是一个优势 在没有外部控制的情况下抑制生物膜形成的方法。现有的抗菌表面包括杀菌剂 表面(例如，抗菌肽或银修饰表面)和抗生物污垢表面(例如，水凝胶或 聚乙二醇基聚合物涂层)，但所有现有方法都不能抑制生物膜 长时间在导尿管上形成。在这里，我们提出了一种新的概念-类液体和无粘性 生物表面，即准液体表面，可潜在地抑制生物膜30天以上。准液体 表面将通过化学粘合将柔性聚合物系在导管材料上。不受束缚的人 End是高度机动的，表现得像流体一样。其创新之处在于将固体/细菌相互作用改变为准 液体/细菌相互作用，在不直接杀灭细菌的情况下抑制多菌生物膜。我们的中央 假设液体状表面将阻止蛋白质吸附，并抑制多菌生物膜作为 长期留置导尿管期间的综合社区。我们将从两个方面验证这一假说：(1)研究 (2)验证临床分离株对生物膜的抑制作用(即， 泌尿系致病菌株)在准液体表面。该团队包括德克萨斯大学达拉斯分校的Pi Dai，他在 生物表面和微流体学，Co-I Palmer，在病原体的微生物学和抗生素耐药性方面的专业知识 细菌，以及我们在德克萨斯大学西南医学中心的合作者齐默恩在管理方面的专业知识 在各种临床环境中复杂的尿路感染。这个为期两年的项目旨在抑制多菌生物被膜 仅从微生物的角度来看，30天是具有挑战性的。这种新型准液体的研制 表面和准液体/细菌相互作用的了解不仅有利于细菌的管理 CAUTIS也为更好地对抗在其他人体植入设备上形成的生物膜开辟了新的途径。

Catheter-associated urinary tract infections (CAUTIs) account for more than 30% of acute care hospital infections. Bacterial pathogens initially colonize and form biofilm on the catheters, and invade the bladder and eventually the upper urinary tracts. Prolonged catheterization (~30 days) can increase the chance of CAUTIs to 100%. Antibiotics prescribed for symptomatic CAUTIs are frequently unable to kill bacteria within the biofilm. Therefore, inhibiting biofilm formation will significantly reduce the chance of CAUTIs. Catheter biofilms are often polymicrobial with mixed bacterial communities. Durable biosurface coatings would be an advantageous approach to inhibit biofilm formation without external control. Existing anti-bacterial surfaces include bactericidal surfaces (e.g., antimicrobial peptide or silver modified surfaces) and anti-biofouling surfaces (e.g., hydrogel or poly(ethyleneglycol) based polymer coatings), but all existing approaches are unable to inhibit biofilm formation on catheters for a prolonged period. Here, we propose a conceptually new fluid-like and non-sticky biosurface, namely a quasi-liquid surface, which can potentially inhibit biofilm for over 30 days. The quasi-liquid surface will be made by tethering flexible polymer onto catheter materials with chemical bonding. The untethered end is highly mobile and behave like a fluid. The innovation is to change the solid/bacterial interaction to quasi- liquid/bacterial interaction and inhibit polymicrobial biofilm without directly killing bacteria. Our central hypothesis is that the fluid-like surface will prevent protein adsorption and inhibit polymicrobial biofilm as an integrated community during long-term catheterization. We will validate the hypothesis with two aims: (1) to study the mechanism of E. coli biofilm inhibition, and (2) to validate biofilm inhibition of clinical isolates (i.e., uropathogenic strains) on the quasi-liquid surface. The team includes PI Dai at UT Dallas with expertise in biosurfaces and microfluidics, Co-I Palmer with expertise in microbiology and antibiotic resistance in pathogenic bacteria, and our collaborator Zimmern at UT Southwestern Medical Center with expertise in the management of complicated UTIs in a variety of clinical settings. This two-year project aims to inhibit polymicrobial biofilm over 30 days that is challenging by a microbiological approach alone. The development of this novel quasi-liquid surface and the understanding of the quasi-liquid/bacterial interaction will not only benefit the management of CAUTIs but also open new avenues to better combat biofilms forming on other human implant devices.