Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Lund, Sweden.
Institute for Molecular Biology of Infectious Diseases, University of Würzburg, Würzburg, Germany.
J Urol. 2014 Feb;191(2):519-28. doi: 10.1016/j.juro.2013.07.060. Epub 2013 Jul 30.
Asymptomatic bacteriuria established by intravesical inoculation of Escherichia coli 83972 is protective in patients with recurrent urinary tract infections. In this randomized, controlled crossover study a total of 3 symptomatic urinary tract infection episodes developed in 2 patients while they carried E. coli 83972. We examined whether virulence reacquisition by symptom isolates may account for the switch from asymptomatic bacteriuria to symptomatic urinary tract infection.
We used E. coli 83972 re-isolates from 2 patients in a prospective study and from another 2 in whom symptoms developed after study completion. We phylogenetically classified the re-isolates, and identified the genomic restriction patterns and gene expression profiles as well as virulence gene structure and phenotypes. In vivo virulence was examined in the murine urinary tract infection model.
The fim, pap, foc, hlyA, fyuA, iuc, iroN, kpsMT K5 and malX genotypes of the symptomatic re-isolates remained unchanged. Bacterial gene expression profiles of flagellated symptomatic re-isolates were unique to each host, providing no evidence of common deregulation. Symptomatic isolates did not differ in virulence from the wild-type strain, as defined in the murine urinary tract infection model by persistence, symptoms or innate immune activation.
The switch from asymptomatic E. coli 83972 carriage to symptomatic urinary tract infection was not explained by reversion to a functional virulence gene repertoire.
通过膀胱内接种大肠杆菌 83972 建立无症状菌尿可保护复发性尿路感染患者。在这项随机对照交叉研究中,有 2 名患者携带大肠杆菌 83972 时共发生 3 次症状性尿路感染发作。我们检查了症状分离株是否通过获得毒力来解释从无症状菌尿到症状性尿路感染的转变。
我们使用 2 名患者的大肠杆菌 83972 再分离株和另 2 名完成研究后出现症状的患者进行前瞻性研究。我们对再分离株进行了系统发育分类,并鉴定了基因组限制图谱和基因表达谱,以及毒力基因结构和表型。在小鼠尿路感染模型中检测了体内毒力。
症状性再分离株的 fim、pap、foc、hlyA、fyuA、iuc、iroN、kpsMT K5 和 malX 基因型保持不变。有鞭毛的症状性再分离株的细菌基因表达谱在每个宿主中都是独特的,没有证据表明存在共同的失调。症状性分离株在小鼠尿路感染模型中通过持久性、症状或先天免疫激活定义的毒力与野生型菌株没有差异。
从无症状大肠杆菌 83972 携带到症状性尿路感染的转变不能用恢复功能的毒力基因谱来解释。