University of Applied Sciences, Biomedical Science, Graz, Austria.
J Bacteriol. 2014 Mar;196(5):931-9. doi: 10.1128/JB.00985-13. Epub 2013 Dec 13.
Biofilm formation on catheters is thought to contribute to persistence of catheter-associated urinary tract infections (CAUTI), which represent the most frequent nosocomial infections. Knowledge of genetic factors for catheter colonization is limited, since their role has not been assessed using physicochemical conditions prevailing in a catheterized human bladder. The current study aimed to combine data from a dynamic catheterized bladder model in vitro with in vivo expression analysis for understanding molecular factors relevant for CAUTI caused by Escherichia coli. By application of the in vitro model that mirrors the physicochemical environment during human infection, we found that an E. coli K-12 mutant defective in type 1 fimbriae, but not isogenic mutants lacking flagella or antigen 43, was outcompeted by the wild-type strain during prolonged catheter colonization. The importance of type 1 fimbriae for catheter colonization was verified using a fimA mutant of uropathogenic E. coli strain CFT073 with human and artificial urine. Orientation of the invertible element (IE) controlling type 1 fimbrial expression in bacterial populations harvested from the colonized catheterized bladder in vitro suggested that the vast majority of catheter-colonizing cells (up to 88%) express type 1 fimbriae. Analysis of IE orientation in E. coli populations harvested from patient catheters revealed that a median level of ∼73% of cells from nine samples have switched on type 1 fimbrial expression. This study supports the utility of the dynamic catheterized bladder model for analyzing catheter colonization factors and highlights a role for type 1 fimbriae during CAUTI.
生物膜在导管上的形成被认为是导致导管相关性尿路感染(CAUTI)持续存在的原因,CAUTI 是最常见的医院获得性感染。由于尚未使用在留置导尿管的人类膀胱中占主导地位的理化条件来评估它们的作用,因此对导管定植的遗传因素的了解有限。本研究旨在将体外动态留置膀胱模型的数据与体内表达分析相结合,以了解与大肠埃希菌引起的 CAUTI 相关的分子因素。通过应用模拟人类感染期间理化环境的体外模型,我们发现,在长时间的导管定植过程中,与野生型菌株相比,一种缺乏 I 型菌毛的大肠埃希菌 K-12 突变体,但不是缺乏鞭毛或抗原 43 的同基因突变体,处于竞争劣势。使用具有人尿和人工尿的尿路致病性大肠埃希菌菌株 CFT073 的 fimA 突变体验证了 I 型菌毛在导管定植中的重要性。从体外培养的留置导管膀胱中定植的细菌群体中分离出的可反转元件(IE)控制 I 型菌毛表达的方向表明,绝大多数导管定植细胞(高达 88%)表达 I 型菌毛。从患者导管中分离出的大肠埃希菌群体中 IE 方向的分析表明,来自 9 个样本的细胞中有中位数为 73%左右的细胞已开启 I 型菌毛的表达。这项研究支持使用动态留置膀胱模型来分析导管定植因素,并强调了 I 型菌毛在 CAUTI 中的作用。