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.

导管相关性尿路感染（CUTI）占急性护理医院感染的30%以上。 细菌病原体最初在导管上定殖并形成生物膜，并侵入膀胱，最终在膀胱中形成细菌。 上尿路延长导管插入时间（约30天）可使发生急性胰腺炎的几率增加至100%。 针对有症状的尿路感染开具的抗生素通常无法杀死生物膜内的细菌。因此，我们认为， 抑制生物膜的形成将显著降低发生膀胱炎的机会。导管生物膜通常 多微生物与混合细菌群落。耐用的生物表面涂层将是有利的 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 表面（例如，抗微生物肽或银改性表面）和抗生物污染表面（例如，水凝胶或 基于聚（乙二醇）的聚合物涂层），但所有现有的方法都不能抑制生物膜 在导管上长时间形成。在这里，我们提出了一个概念上新的流体状和非粘性 生物表面，即准液体表面，其可以潜在地抑制生物膜超过30天。准液体 表面将通过将柔性聚合物用化学键连接到导管材料上而制成。The untethered 末端是高度移动的且表现得像流体。创新是将固体/细菌相互作用改变为准- 液体/细菌相互作用并抑制多微生物生物膜而不直接杀死细菌。我们的中央 一种假设是，流体状表面将阻止蛋白质吸附并抑制多微生物生物膜作为一种生物膜。 长期导尿期间的综合社区。我们将验证假设有两个目的：（1）研究 对E.大肠杆菌生物膜抑制，和（2）验证临床分离株的生物膜抑制（即， 尿路致病性菌株）在准液体表面上。该团队包括UT达拉斯的PI Dai， 生物表面和微流体，Co-I Palmer在病原微生物和抗生素耐药性方面具有专业知识， 细菌，我们的合作者Zimmern在UT西南医学中心的管理专业知识 在各种临床环境中的复杂性尿路感染。这个为期两年的项目旨在抑制多微生物生物膜超过 30天，这是具有挑战性的微生物方法单独。这种新型准液体的发展 表面和准液体/细菌相互作用的理解将不仅有利于管理 同时也为更好地对抗其他人体植入设备上形成的生物膜开辟了新的途径。