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LubriShieldTM——一种永久性导尿管涂层,可在体外防止尿路病原体生物膜形成,且不依赖于宿主蛋白调理。

LubriShieldTM-A permanent urinary catheter coating that prevents uropathogen biofilm formation in vitro independent of host protein conditioning.

作者信息

Romero Ana I, Surkov Serhiy, Wirsén Per, Brookes Graeme, Bergström Linda, Tejbrant Jan, Dhamo Elena, Wilks Sandra, Bryant Catherine, Andersson Jan

机构信息

CytaCoat AB, Solna, Sweden.

School of Biological Sciences, University of Southampton, Southampton, United Kingdom.

出版信息

PLoS One. 2025 Jul 10;20(7):e0328167. doi: 10.1371/journal.pone.0328167. eCollection 2025.

Abstract

Catheter-associated urinary tract infection is one of the most common healthcare-associated infections, with biofilm formation playing a key role in its pathogenesis. Indwelling medical devices introduce ideal pathways inside the body for pathogens and feature surfaces conducive to biofilm development, often leading to severe clinical infections recalcitrant to antimicrobials. When bacteria and fungi switch to biofilm mode of growth, they produce a matrix in the form of extracellular polymeric substances (EPS). This creates a unique environment for growing virulent colonisers and persisting cells while forming a shielding barrier against immune system attacks, antimicrobial agents and mechanical removal by fluid shear forces. To address this challenge, LubriShieldTM - a novel permanent coating - was invented and evenly applied to both internal and external surfaces of indwelling urinary Foley catheters. Without releasing active substances, it effectively prevented pathogens from producing biofilm. The superhydrophilic coating, incorporating a proprietary anti-fouling ligand, significantly inhibited colonising uropathogens from forming biofilm for up to 14 days in artificial urine medium without microbial killing (up to 99% reduction, P < 0.001). In a glass bladder flow model, LubriShieldTM still significantly reduced biofilm formation by 83% (P < 0.0001). Importantly, LubriShield™ maintained its antibiofilm efficacy even after conditioning with fibrinogen, a host-derived protein known to promote bacterial attachment (P = 0.007). RNA-seq analysis revealed significant downregulation of genes associated with microbial EPS formation on the coated surfaces. Additionally, microorganisms adhering to LubriShieldTM coated catheters showed a 78% increased susceptibility to antibiotics compared to those on uncoated catheters (P = 0.004).

摘要

导尿管相关尿路感染是最常见的医疗保健相关感染之一,生物膜形成在其发病机制中起关键作用。留置医疗器械为病原体在体内引入了理想的途径,其表面有利于生物膜的形成,常常导致严重的临床感染,对抗菌药物具有耐药性。当细菌和真菌转变为生物膜生长模式时,它们会产生一种细胞外聚合物(EPS)形式的基质。这为有毒力的定植菌和持续存在的细胞创造了独特的生长环境,同时形成了一道抵御免疫系统攻击、抗菌药物和流体剪切力机械清除的屏障。为应对这一挑战,发明了一种新型永久性涂层LubriShieldTM,并将其均匀地应用于留置导尿管的内外表面。它不释放活性物质,却能有效防止病原体形成生物膜。这种超亲水涂层含有一种专利防污配体,在人工尿液培养基中,能显著抑制尿路致病性定植菌形成生物膜长达14天,且无杀菌作用(减少高达99%,P < 0.001)。在玻璃膀胱流动模型中,LubriShieldTM仍能显著减少生物膜形成,降幅达83%(P < 0.0001)。重要的是,即使在用纤维蛋白原预处理后,LubriShield™仍保持其抗生物膜功效,纤维蛋白原是一种已知能促进细菌黏附的宿主来源蛋白(P = 0.007)。RNA测序分析显示,在涂层表面,与微生物EPS形成相关的基因显著下调。此外,与未涂层导尿管上的微生物相比,附着在LubriShieldTM涂层导尿管上的微生物对抗生素的敏感性增加了78%(P = 0.004)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf50/12244716/fe7439b56e0d/pone.0328167.g001.jpg

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