Durable fluid-like surface for sustainable biofilm inhibition

耐用的流体状表面可实现可持续的生物膜抑制

• 批准号: 10646770
• 负责人: Xianming Dai
• 金额: $ 7.8万
• 依托单位: UNIVERSITY OF TEXAS DALLAS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10646770
• 关键词: Accounting; Adsorption; Anti-Bacterial Agents; Antibiotic Resistance; Antibiotics; Bacteria; Bacterial Adhesion; Biological; Bladder; Catheter Management; Catheterization; Catheters; Cells; Charge; Clinical; Collection; Communities; Development; Electrostatics; Enterococcus faecalis; Escherichia coli; Gram-Negative Bacteria; Hour; Human; Hydrogels; Invaded; Liquid substance; Medical center; Microbial Biofilms; Microbiology; Microfluidics; Molecular; Nosocomial Infections; Nucleic Acids; Outcomes Research; Patients; Polymers; Property; Proteins; Pseudomonas aeruginosa; Sampling; Silanes; Silicones; Silver; Sodium Chloride; Solid; Surface; Testing; Time; Urinary tract; Urine; Uropathogen; Viscosity; acute care; antimicrobial peptide; bacterial community; bactericide; catheter associated UTI; chemical bond; combat; ethylene glycol; flexibility; fluidity; implantable device; innovation; interfacial; intermolecular interaction; novel; pathogen; pathogenic bacteria; polymicrobial biofilm; prevent; surface coating

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.

与导管相关的尿路感染（CAUTIS）占急性医院感染的30％以上。 细菌病原体最初在导管上定植并形成生物膜，并入侵膀胱，最终 上尿路。长时间的导管插入术（约30天）可以将尾tis的机会增加到100％。 针对有症状的小肠规定的抗生素通常无法在生物膜内杀死细菌。所以， 抑制生物膜的形成将大大减少尾tis的机会。导管生物膜通常是 与混合细菌群落的多数菌属。耐用的生物表面涂料将是一个有利的 抑制生物膜形成而无需外部控制的方法。现有的抗细菌表面包括杀菌 表面（例如，抗菌肽或银色改性表面）和抗双燃料表面（例如水凝胶或水凝胶或 聚（乙二醇）的聚合物涂层），但所有现有方法均无法抑制生物膜 长时间在导管上形成。在这里，我们在概念上提出了一种新的流体和不变的味道 生物表面，即准液体表面，可以潜在地抑制30天以上的生物膜。准液体 表面将通过将柔性聚合物绑定到具有化学键合的导管材料上。无限制 结束是高度流动性的，表现就像是流体。创新是将固体/细菌相互作用更改为准 液体/细菌相互作用并抑制多数生物膜，而无需直接杀死细菌。我们的中心 假设是液体样表面将防止蛋白质吸附并抑制多数生物膜作为一种 长期导管插入期间综合社区。我们将以两个目的验证假设：（1）研究 大肠杆菌生物膜抑制的机制和（2）验证生物膜抑制临床分离株的机制（即 准液体表面上的尿液发育菌株。该团队在UT Dallas中包括Pi Dai，并具有专业知识 生物曲面和微流体，Co-i Palmer在致病性中具有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UT西南医学中心的合作者Zimmern具有专业知识 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数生物膜 仅通过微生物学方法而挑战的30天。这个小说的准液体的发展 表面和对准液/细菌相互作用的理解不仅会受益 剖腹产，但也开放了新的途径，以更好地打击其他人类植入设备上形成的生物膜。