Orgin of multidrug resistant uropathogenic E. coli

多重耐药性尿路致病性大肠杆菌的起源

• 批准号: 7151208
• 负责人: LEE W RILEY
• 金额: $ 28.82万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7151208
• 关键词: Animal Feed; Animal Sources; Animals; Antibiotic Resistance; Antibiotics; California; Class; Clinical; Collection; Communicable Diseases; Communities; Disease; Dose; Drug resistance; Enterobacteriaceae; Epidemiology; Escherichia coli; Escherichia coli Infections; Escherichia coli drug resistance; Food; Genes; Genetic; Goals; Growth; Human; Incidence; Infection Control; Integrons; Knowledge; Lead; Mediating; Midwestern United States; Multi-Drug Resistance; Organism; Population; Prevalence; Resistance; Salmonella enterica; Salmonella typhimurium; Serotyping; Source; United States; Urinary tract infection; Uropathogenic E. coli; Woman; antimicrobial drug; base; college; foodborne; genetic element; improved; pressure; promoter

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.

描述（由申请人提供）：这是一项建议，以表征与尿路感染（UTI）相关的大肠杆菌多种耐药克隆的起源。社区获得的耐药UTI是全球抗药性的传染病问题。我们最近的研究表明，通过引入耐药大肠杆菌菌株的克隆组，社区中的抗药性UTI患病率突然增加。在加利福尼亚州的一项基于人群的研究中，我们发现属于一个名为CGA的单一克隆人群的E.卷积是大学校园中女性中耐药的50％。在美国中西部的两个大学校园中，在耐药的UTI大肠杆菌分离株中发现了同一克隆组。我们提出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中的耐药性是由称为携带基因盒的遗传元素介导的，这些元件携带了编码抗生素耐药性的基因盒。在这个项目中，我们希望证明，耐药性大肠杆菌菌株在暴露于抗生素亚治性剂量的食用动物储层中获得了其耐药性决定因素。我们假设这些盒子从动物肠杆菌科中转移到动物储层中的大肠杆菌菌株。然后，这些大肠杆菌菌株会导致女性UTI。我们将首先分析我们大量的抗药性肝癌大肠杆菌分离株，这些大肠杆菌是从基于人群的整合性次数，阶级和分布的人群研究中获得的，以及盒式类型和序列。然后，我们将将这些盒式磁带序列与特征良好的多药抗性动物大肠杆菌分离株以及耐多药耐鼠伤寒沙门氏菌DT104分离株进行比较。这些发现不仅应确定主要致病性肠道科的耐药性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，美国在范围和疾病范围中比以前更大的美国更大。这些知识应导致对耐药性感染疾病的控制的改善。