TRANSMISSION DYNAMICS OF MULTI-DRUG RESISTANT UROPATHOGENIC E. coli IN BANGLADESH

 描述（由申请方提供）：多药耐药（MDR）、社区获得性尿路感染（UTI）可导致严重的医学并发症，包括败血症。特别值得关注的是对第三代头孢菌素（3GC）和碳青霉烯类的耐药性不断上升。在世界上大多数地区，社区获得性尿路感染的很大一部分是由有限的多药耐药大肠杆菌引起的。属于相关谱系的大肠杆菌菌株，或携带致病性和环境革兰氏阴性菌共有的耐药基因的大肠杆菌菌株。研究表明，MDR尿路致病性E.大肠杆菌（UPEC）与大肠杆菌（E.大肠杆菌引起家禽感染，表明抗生素耐药UPEC的潜在食源性传播。然而，需要进行更多的研究才能准确量化食用和食用动物作为大肠杆菌宿主的贡献。大肠杆菌病原体导致耐药UTI。我们的项目将研究MDR UPEC在孟加拉国达卡的传播动力学，作为UPEC克隆谱系及其耐药决定因素如何在社区传播而不是在医疗环境中传播的范例。我们计划在孟加拉国开展该项目，因为该国沿着次大陆的其他国家似乎是全球观察到的许多多重耐药肠杆菌科微生物和谱系的重要储存地。我们将分三个阶段进行这项研究：首先，我们将确定 MDR E.大肠埃希菌在UTI患者中的表达（yr 1至yr3.5），并确定与MDR UTI相关的风险因素。其次，我们将研究MDR UPEC的零售食品、水和家禽来源（1.5 - 3.5年）。最后，我们将比较UTI和食物来源分离株的抗生素耐药性和基因型特征，以追踪与社区获得性UTI相关的UPEC传播模式（yr 2-yr4.5）。共享其遗传谱系的分离株的全基因组测序（基于PFGE和MLST数据）将用于确定传播方向。该项目总共需要60个月。这个项目将使我们能够定量地确定影响，如果有的话，食物和食用动物作为水库的E。大肠杆菌病原体对一种重要而常见的社区获得性感染-UTI的作用。如果这些水库最终成为这些感染的主要来源，我们将能够制定更有针对性的公共卫生干预措施来预防它们。

 DESCRIPTION (provided by applicant): Multidrug-resistant (MDR), community-acquired urinary tract infections (UTI) contribute to severe medical complications, including sepsis. Of particular concern is the rising resistance against third generation cephalosporins (3GC) and carbapenems. A large proportion of community-acquired UTI in most regions of the world are caused by a limited set of multi-drug resistant E. coli strains belonging to related lineages, or E coli strains that harbor drug resistance genes shared by pathogenic and environmental Gram negative bacteria. Studies have shown that MDR uropathogenic E. coli (UPEC) share the same genetic lineages with E. coli causing infection in poultry, indicating potential foodborne transmissions of antibiotic resistant UPEC. However, additional research is required to accurately quantify the contribution of food and food animals as reservoirs for E. coli pathogens that cause drug-resistant UTI. Our project will examine the transmission dynamics of MDR UPEC in Dhaka, Bangladesh as a paradigm of how UPEC clonal lineages and their drug-resistance determinants disseminate in community as opposed to healthcare settings. We plan to do this project in Bangladesh as this country along with other countries in the sub-continent appear to be an important reservoir of many multidrug-resistant Enterobacteriaceae organisms and lineages that are observed globally. We will do this study in 3 phases: first we will determine the trend in prevalence of MDR E. coli in patients with UTI (yr1 to yr3.5) and identify risk factor associated with MDR UTI. Second, we will study the retail food, water and poultry sources for MDR UPEC (yr1.5-yr3.5). Finally, we will compare the antibiotic resistance profiles and genotypic characteristics of isolates from UTI and food sources to track mode of transmission of UPEC associated with community acquired UTI (yr2-yr4.5). Whole genome sequencing of isolates sharing their genetic lineages (based on PFGE and MLST data) will be used to determine the direction of transmission. Altogether, the project will take 60 months. This project will enable us to quantitatively determine the impact, if any, of food and food-producing animals as reservoirs for E. coli pathogens on an important and common community-acquired infection-UTI. If such reservoirs turn out to be a major source of these infections, we will be able to devise more focused public health interventions to prevent them.