Orgin of multidrug resistant uropathogenic E. coli

描述（由申请人提供）：这是重新提交的一份描述大肠杆菌多药耐药克隆起源的提案。大肠杆菌相关的尿路感染（UTI）。社区获得性多重耐药尿路感染是一种新出现的耐药传染病问题。我们最近的研究表明，社区中耐药UTI的流行率可以通过引入耐药大肠杆菌的克隆群而突然增加。大肠杆菌菌株。在加州的一项基于人群的研究中，我们发现E.属于单一克隆群CgA的螺旋是大学校园女性中50%耐药UTI的原因。在耐药UTIE中鉴定出相同的克隆群。从美国中西部两所大学校园分离的大肠杆菌。我们认为这些菌株是通过受污染的食品传播的。我们还发现，这些大肠杆菌的耐药性。大肠杆菌分离株是由称为整合子的遗传元件介导的，整合子携带编码抗生素抗性的基因盒。本课题旨在证明耐药尿路致病性大肠杆菌的耐药性。大肠杆菌菌株在食用动物接触亚治疗剂量的抗生素时获得其耐药性决定因素。我们假设这些表达盒是从动物肠杆菌科转移到大肠杆菌的。大肠杆菌菌株。这些E.大肠杆菌菌株随后会导致女性尿路感染。我们将首先分析我们收集的大量耐药尿路致病性大肠杆菌。从基于人群的研究中获得的大肠杆菌分离株的整合子流行率、类别和分布，以及盒类型和序列。然后，我们将比较这些盒序列的充分表征的多药耐药动物E。大肠杆菌分离株，以及多重耐药鼠伤寒沙门氏菌DT 104分离株。这些发现不仅可以确定主要致病性肠杆菌科物种耐药决定因素的分布和程度，而且如果我们的发现支持食源性UTI假说，我们将证明美国食源性耐药传染病问题的范围和疾病谱比以前认为的要大得多。这一知识应有助于改进对耐药传染病的控制。

DESCRIPTION (provided by applicant): This is a resubmission of a proposal to characterize the origin of multidrug-resistant clones of E. coli associated with urinary tract infections (UTI). Community-acquired multidrug-resistant UTI is an emerging drug-resistant infectious disease problem worldwide. Our recent studies suggest that drug resistant UTI prevalence in a community can suddenly increase by the introduction of a clonal group of drug-resistant E. coli strains. In a population-based study in California, we found that strains of E. coil belonging to a single clonal group called CgA were responsible for 50% of drug-resistant UTI among women in a college campus. The same clonal group was identified among drug-resistant UTI E. coli isolates from two college campuses in Midwestern United States. We proposed that these strains were spread by contaminated food products. We also showed that drug resistance in these E. coli isolates is mediated by genetic elements called integrons that carry gene cassettes that encode antibiotic resistance. In this project, we wish to demonstrate that drug-resistant uropathogenic E. coli strains acquire their resistance determinants in the food animal reservoir exposed to subtherapeutic doses of antibiotics. We hypothesize that these cassettes are transferred from animal Enterobacteriaceae species to E. coli strains in the animal reservoir. These E. coli strains then cause UTI in women. We will first analyze our large collection of drug-resistant uropathogenic E. coli isolates obtained from population-based studies for integron prevalence, class, and distribution, as well as for cassette type and sequences. We will then compare these cassette sequences to those of well-characterized multidrug-resistant animal E. coli isolates, as well as multidrug-resistant Salmonella typhimurium DT104 isolates. These findings should identify not only the distribution and extent of drug resistance determinants in major pathogenic Enteropacteriaceae species, but if our findings support the foodborne UTI hypothesis, we would be demonstrating that foodborne drug-resistant infectious disease problems in the United States are much greater in scope and disease spectrum than previously believed. This knowledge should lead to the implementation of improved control of drug-resistant infectious diseases.