Dietary copper reconfigures pathogen growth

膳食铜重新配置病原体生长

基本信息

批准号：
9796793
负责人：
Andreas J Baumler
金额：
$ 19.63万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-06 至 2021-05-31
项目状态：
已结题

项目摘要

Project Summary The vertebrate large intestine is host to a large microbial community that confers benefit by functioning in host nutrition, immune education and colonization resistance against enteric pathogens. The composition of the gut microbiota varies with the diet, but little is known about how shifts in the microbiota composition affect functionality, such as the ability to confer colonization resistance against enteric pathogens. Here we will investigate how dietary copper supplementation, a common practice to improve growth performance in livestock, alters colonization resistance against the enteric pathogen Salmonella enterica serovar (S.) Typhimurium. Our central hypothesis is that dietary copper supplementation depletes propionate- producing Bacteroidaceae from the gut microbiota, thereby conferring a fitness advantage for S. Typhimurium strains carrying the sopE gene. We will test key aspects of our hypothesis and accomplish the objectives of this application using the logical and innovative approach outlined in the following specific aim: Determine whether a dietary copper-induced Bacteroidaceae depletion lowers colonization resistance against S. Typhimurium lysogenized with a sopE-encoding prophage. It is our expectation that the outcome of our experiments will show that diet-induced shifts in the gut microbiota composition in livestock can select for enteric pathogens carrying new virulence factors, which is relevant for human health because livestock carriage is a common route for introducing the pathogen into our food supply. This outcome will be significant because it will usher in the novel concept that diet-induced shifts in the microbiota composition can select for new virulence factors in enteric pathogens, a paradigm of broad interest to researchers in bacterial pathogenesis, microbiota and nutrition.

项目概要脊椎动物大肠是一个大型微生物群落的宿主，它通过以下方式带来益处：在宿主营养、免疫教育和肠道定植抵抗中发挥作用病原体。肠道微生物群的组成随饮食而变化，但人们对此知之甚少微生物群组成的变化如何影响功能，例如赋予的能力对肠道病原体的定植抵抗力。在这里我们将研究膳食铜如何补充是提高牲畜生长性能的常见做法，它改变了对肠道病原体沙门氏菌血清型 (S.) 的定植抗性鼠伤寒杆菌。我们的中心假设是膳食补充铜会消耗丙酸- 从肠道微生物群中产生拟杆菌科，从而赋予了拟杆菌的适应性优势。携带 sopE 基因的鼠伤寒菌株。我们将测试我们假设的关键方面使用中概述的逻辑和创新方法来实现此应用程序的目标具体目标如下：确定饮食中的铜是否会引起拟杆菌科细菌的消耗降低对具有 sopE 编码的溶原性鼠伤寒沙门氏菌的定植抗性原噬菌体。我们期望我们的实验结果将表明饮食引起的家畜肠道微生物群组成的变化可以选择携带新的肠道病原体毒力因子，与人类健康相关，因为牲畜运输是一种常见的将病原体引入我们的食品供应的途径。这一结果将意义重大，因为它将引入一个新概念，即饮食引起的微生物群组成的变化可以选择对于肠道病原体的新毒力因子，这是研究人员广泛感兴趣的范式细菌发病机制、微生物群和营养。