Orgin of multidrug resistant uropathogenic E. coli

描述（由申请人提供）：这是一份关于与尿路感染（UTI）相关的大肠杆菌多药耐药克隆起源特征的提案的重新提交。社区获得性多药耐药尿路感染是世界范围内新出现的耐药传染病问题。我们最近的研究表明，社区中耐药尿路感染的患病率可能会因引入耐药大肠杆菌菌株克隆群而突然增加。在加利福尼亚的一项基于人群的研究中，我们发现属于CgA单克隆群的E. coil菌株在大学校园中造成了50%的耐药UTI。在美国中西部两所大学校园的耐药UTI大肠杆菌分离株中鉴定出相同的克隆群。我们认为这些菌株是通过受污染的食品传播的。我们还表明，这些大肠杆菌分离株的耐药性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耐药性的基因盒。在这个项目中，我们希望证明耐药尿路致病性大肠杆菌菌株在暴露于亚治疗剂量抗生素的食用动物库中获得其耐药决定因素。我们假设这些盒式细菌是从动物肠杆菌科物种转移到动物储存库中的大肠杆菌菌株。这些大肠杆菌菌株会导致女性感染尿路感染。我们将首先分析从基于人群的研究中获得的大量耐药尿路致病性大肠杆菌分离株，以了解整合子的流行程度、类别和分布，以及盒式类型和序列。然后，我们将这些盒式序列与具有良好特征的耐多药动物大肠杆菌分离株以及耐多药鼠伤寒沙门氏菌DT104分离株进行比较。这些发现不仅应该确定主要致病性肠杆菌科物种中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假设，我们将证明美国食源性耐药传染病问题的范围和疾病范围比以前认为的要大得多。这方面的知识应有助于加强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.