Zhu Zhiling, Yu Fei, Chen Haoqing, Wang Jun, Lopez Analette I, Chen Quan, Li Siheng, Long Yuyu, Darouiche Rabih O, Hull Richard A, Zhang Lijuan, Cai Chengzhi
Department of Chemistry, University of Houston, Houston, TX 77204, United States.
School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, China.
Acta Biomater. 2017 Dec;64:200-210. doi: 10.1016/j.actbio.2017.10.008. Epub 2017 Oct 9.
Bacterial interference using non-pathogenic Escherichia coli 83972 is a novel strategy for preventing catheter-associated urinary tract infection (CAUTI). Crucial to the success of this strategy is to establish a high coverage and stable biofilm of the non-pathogenic bacteria on the catheter surface. However, this non-pathogenic strain is sluggish to form biofilms on silicone as the most widely used material for urinary catheters. We have addressed this issue by modifying the silicone catheter surfaces with mannosides that promote the biofilm formation, but the stability of the non-pathogenic biofilms challenged by uropathogens over long-term remains a concern. Herein, we report our study on the stability of the non-pathogenic biofilms grown on propynylphenyl mannoside-modified silicone. The result shows that 94% non-pathogenic bacteria were retained on the modified silicone under >0.5 Pa shear stress. After being challenged by three multidrug-resistant uropathogenic isolates in artificial urine for 11 days, large amounts (>4 × 10 CFU cm) of the non-pathogenic bacteria remained on the surfaces. These non-pathogenic biofilms reduced the colonization of the uropathogens by >3.2-log.
In bacterial interference, the non-pathogenic Escherichia coli strains are sluggish to form biofilms on the catheter surfaces, due to rapid removal by urine flow. We have demonstrated a solution to this bottleneck by pre-functionalization of mannosides on the silicone surfaces to promote E. coli biofilm formation. A pre-conjugated high affinity propynylphenyl mannoside ligand tethered to the nanometric amino-terminated poly(amido amine) (PAMAM) dendrimer is used for binding to a major E. coli adhesin FimH. It greatly improves the efficiency for the catheter modification, the non-pathogenic biofilm coverage, as well as the (long-term) stability for prevention of uropathogen infections.
使用非致病性大肠杆菌83972进行细菌干扰是预防导管相关尿路感染（CAUTI）的一种新策略。该策略成功的关键在于在导管表面建立高覆盖率且稳定的非致病性细菌生物膜。然而，这种非致病性菌株在作为导尿管最广泛使用材料的硅胶上形成生物膜的速度较慢。我们通过用促进生物膜形成的甘露糖苷修饰硅胶导管表面来解决这个问题，但长期受到尿路病原体挑战的非致病性生物膜的稳定性仍然是一个问题。在此，我们报告了我们对在丙炔基苯基甘露糖苷修饰的硅胶上生长的非致病性生物膜稳定性的研究。结果表明，在>0.5 Pa的剪切应力下，94%的非致病性细菌保留在修饰后的硅胶上。在人工尿液中受到三种耐多药尿路致病性分离株攻击11天后，大量（>4×10 CFU/cm）的非致病性细菌仍留在表面。这些非致病性生物膜使尿路病原体的定植减少了>3.2个对数级。
在细菌干扰中，由于尿液流动导致快速清除，非致病性大肠杆菌菌株在导管表面形成生物膜的速度较慢。我们通过在硅胶表面预功能化甘露糖苷以促进大肠杆菌生物膜形成，展示了一种解决这一瓶颈的方法。一种与纳米级氨基末端聚（酰胺胺）（PAMAM）树枝状大分子连接的预共轭高亲和力丙炔基苯基甘露糖苷配体用于与主要的大肠杆菌粘附素FimH结合。它极大地提高了导管修饰的效率、非致病性生物膜的覆盖率以及预防尿路病原体感染的（长期）稳定性。
