Orgin of multidrug resistant uropathogenic E. coli

描述(由申请人提供)：这是一项重新提交的提案，该提案旨在确定与尿路感染(UTI)相关的多重耐药克隆的来源。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，通过引入一组耐药大肠杆菌菌株，社区中耐药UTI的流行率可能会突然增加。在加利福尼亚州的一项以人群为基础的研究中，我们发现属于一个称为CGA的克隆组的E.cos菌株导致了大学校园女性耐药尿路感染的50%。在来自美国中西部两所大学校园的耐药UTI大肠杆菌分离株中，发现了相同的克隆群。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，这些基因元件携带编码抗生素耐药性的基因盒。在这个项目中，我们希望证明耐药致尿路病原性大肠杆菌菌株在接触亚治疗剂量抗生素的食用动物储存库中获得它们的耐药性决定因素。我们假设这些盒是从动物肠杆菌科物种转移到动物储藏室中的大肠杆菌菌株。然后，这些大肠杆菌菌株会导致女性尿路感染。我们将首先分析我们从人群研究中获得的大量耐药致尿路病原性大肠杆菌分离株，这些研究包括整合子的流行、分类和分布，以及盒类型和序列。然后，我们将把这些盒式磁带序列与具有良好特性的多重耐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耐药决定因素在主要致病肠杆菌科物种中的分布和程度，而且如果我们的发现支持食源性UTI假说，我们将证明美国的食源性耐药传染病问题在范围和疾病谱上比之前认为的要大得多。这方面的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.