Characterization of pyelonephritis and cystitis E. coli isolates – Comparison of bacterial traits involved in colonization of the lower or upper urinary tract

肾盂肾炎和膀胱炎大肠杆菌分离株的特征 â 比较参与下尿路或上尿路定植的细菌性状

• 批准号: 509468133
• 负责人: Professor Dr. Ulrich Dobrindt
• 金额: --
• 依托单位: Bereich Mikrobielle Genomplastizität - Molekulare Infektionsbiologie
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/509468133?language=en
• 关键词: Characterization; pyelonephritis; cystitis; E.; coli

Uropathogenic Escherichia coli (UPEC) are the most common pathogens of lower and upper urinary tract infections (UTIs). Kidneys and urinary bladders differ significantly, among other things, anatomically and in terms of an immune response. We assume that UPEC adapt to the respective environment which profoundly differs between kidney and bladder, e.g., in terms of tonicity and nutrient availability. There is also epidemiological evidence that pyelonephritis and cystitis isolates differ. We hypothesize that UPEC employ different adaptation strategies during upper and lower UTI. We will perform comparative genomics on pyelonephritis and cystitis isolates to identify bacterial factors that determine pathogenicity in the kidneys and bladder, respectively. Using selected virulence factors and small regulatory RNAs as examples, we will investigate bacterial adaptation in the kidney at the gene regulatory and functional levels. We will analyze global bacterial and host gene expression in the infected kidney using dual RNA-seq in a murine infection model. Furthermore, we will use reporter gene modules, tissue clearing, and lightsheet microscopy as well as two-photon microscopy to follow the expression of these factors in the infected organ or during the course of infection. Further functional characterization will include in vitro studies of the interaction between UPEC isolates or defined mutants and isolated collecting ducts under different growth and infection conditions.

尿路致病性大肠杆菌（UPEC）是上尿路感染（UTIs）最常见的病原体。肾脏和膀胱在解剖学和免疫反应方面有很大的不同。我们假设UPEC适应肾脏和膀胱之间深刻不同的相应环境，例如，在张力和营养的可用性方面。还有流行病学证据表明肾盂肾炎和膀胱炎分离株不同。我们假设UPEC采用不同的适应策略，在上部和下部UTI。我们将对肾盂肾炎和膀胱炎分离株进行比较基因组学研究，以确定分别决定肾脏和膀胱致病性的细菌因子。使用选定的毒力因子和小调控RNA为例，我们将研究细菌适应在肾脏的基因调控和功能水平。我们将在小鼠感染模型中使用双重RNA-seq分析感染肾脏中的整体细菌和宿主基因表达。此外，我们将使用报告基因模块，组织清除，光片显微镜以及双光子显微镜来跟踪这些因子在感染器官或感染过程中的表达。进一步的功能表征将包括在不同的生长和感染条件下UPEC分离株或确定的突变体和分离的集合管之间的相互作用的体外研究。