ROLE OF THE BLADDER EPITHELIUM IN RESPONSE TO ENTEROCOCCUS FAECALIS UTI

膀胱上皮在应对粪肠球菌尿路感染中的作用

• 批准号: 8167831
• 负责人: Lynn E Hancock
• 金额: $ 7.3万
• 依托单位: KANSAS STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167831
• 关键词: Address; Animals; Bladder; Computer Retrieval of Information on Scientific Projects Database; Encapsulated; Enterococcus faecalis; Epithelium; Funding; Gelatinases; Genetic; Grant; Histopathology; Hospitals; Immune; In Vitro; Infection; Institution; Kidney; Mediating; Modeling; Mus; Organism; Outcome Measure; Peptide Hydrolases; Play; Process; Production; Relative (related person); Research; Research Personnel; Resources; Role; Serine Protease; Severities; Site; Source; System; Tissues; United States; United States National Institutes of Health; Urinary tract; Urinary tract infection; Urine; ascending urinary tract infection; capsule; extracellular; microbial; mutant; neutrophil; nosocomial UTI; pathogen; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. It is estimated that Enteroccus faecalis causes 300,000-500,000 cases of nosocomial urinary tract infection (UTI) each year in the United States, placing it as the second leading cause of UTI's in hospitals. In order to establish infection in the host, pathogens must adapt strategies to overcome the host innate immune defense system. We have previously shown that pathogenic-derived lineages of E. faecalis possess an antiphagocytic capsule that protects the organism in vitro against neutrophil-mediated opsonophagocytosis. Roughly 50% of E. faecalis isolates possess the genetic locus that encodes the capsule biosynthetic machinery. In addition, the presence of the capsule enhances the survival of E. faecalis strains at extraintestinal sites. What role the capsule plays in establishing infection in the urinary tract is one focus of the present study. To address this question, we will use a recently established murine ascending UTI model and compare a wild-type encapsulated strain with two isogenic capsule mutants that either result in structural alterations to the capsule (cpsF) or eliminate capsule production altogether (cpsC). The outcome measures will be assessed by quantifying the bacterial burden in the urine, bladder, and kidneys of infected animals. Bladder and kidney tissues will also be processed to examine the histopathology resulting from these infections. In addition to capsule, other microbial factors that could potentially alter clearance by the innate defense system include two extracellular proteases (gelatinase and serine protease). Protease mutants will also be compared in the UTI model to determine their relative contribution to the severity of infection.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 据估计，粪肠球菌每年在美国引起300，000 - 500，000例医院尿路感染（UTI），将其作为医院中UTI的第二大原因。 为了在宿主中建立感染，病原体必须调整策略以克服宿主的先天免疫防御系统。 我们以前已经表明，致病性衍生的E。粪肠球菌具有抗吞噬囊，其在体外保护生物体免受嗜中性粒细胞介导的调理吞噬作用。 约50%的E。粪肠球菌分离株具有编码荚膜生物合成机制的遗传基因座。 此外，胶囊的存在增强了E.肠外部位的粪菌菌株。 胶囊在建立尿路感染中所起的作用是本研究的焦点之一。 为了解决这个问题，我们将使用最近建立的小鼠上行性UTI模型，并将野生型包囊菌株与两种导致胶囊结构改变（cpSF）或完全消除胶囊生产（cpSC）的等基因胶囊突变体进行比较。 将通过量化感染动物尿液、膀胱和肾脏中的细菌负荷来评估结局指标。 还将处理膀胱和肾脏组织，以检查这些感染引起的组织病理学。 除荚膜外，其他可能改变先天防御系统清除率的微生物因素包括两种细胞外蛋白酶（明胶酶和丝氨酸蛋白酶）。 还将在UTI模型中比较蛋白酶突变体，以确定其对感染严重程度的相对贡献。