Campylobacter jejuni colonization and the resident microbiota

空肠弯曲菌定植和常驻微生物群

• 批准号: 8994717
• 负责人: Jorge E Galan
• 金额: $ 20.81万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-15 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8994717
• 关键词: Address; Animal Model; Area; Base Sequence; Biology; Campylobacter jejuni; Chin; Chronic; Communicable Diseases; Complication; Coupling; Culture Media; Development; Diarrhea; Disease; Enteral; Escherichia coli O157:H7; Food; Food Chain; Food Industry; Foundations; Future; Genes; Genetic; Genetic Screening; Genome; Gnotobiotic; Goals; Guillain-Barré Syndrome; Health; Human; Individual; Infection; Inflammatory; Intestines; Knowledge; Laboratories; Lead; Libraries; Metabolic; Metabolic Pathway; Metabolism; Mus; Mutagenesis; Nutrient; Oxidants; Pathogenesis; Pathogenicity; Patients; Respiratory Chain; Role; Salmonella; Salmonella typhimurium; Secure; Shigella; Surveys; Syndrome; Therapeutic; United States; Virulence Factors; base; combat; enteric pathogen; foodborne; genetic approach; germ free condition; in vivo; metabolic abnormality assessment; microbial; microbiota; mouse model; mutant; next generation sequencing; novel strategies; novel therapeutic intervention; pathogen; respiratory

 DESCRIPTION (provided by applicant): Campylobacter jejuni is the most common cause of food-born diarrhea in the United States. Although it is most often associated with self-limiting diarrheal disease, a small proportion of infected patients develop a more serious neuro-degenerative complication known as Guillain-Barré Syndrome. Despite many important advances in the field, still remarkably little is known about its mechanisms of pathogenicity. C. jejuni has the ability to efficiently colonize the intestine of a broad range of hosts, which allow this pathogen to gain access to the food chain thus presenting major challenges to the food industry. Therefore, the study of C. jejuni colonization offers unique opportunities to gain knowledge about mechanisms by which a pathogen can establish itself in the intestinal track of its hosts and successfully compete with the resident microbiota. Securing nutrients and terminal electron acceptors for their respiratory chain are central to the ability of pathogens to colonize given niche. Although knowledge of microbial metabolism in model organisms is substantial, much less is known about metabolism during infection. The versatility of microbial pathogens to acquire nutrients is emerging as central for their ability to colonize in the face of steep competition from the resident microbiota. Many basic parameters of C. jejuni central metabolism, its ability to utilize nutrients, and several aspects of its diversified respiratory chins have been established. However, these studies have been largely carried out in culture medium and therefore the understanding of C. jejuni metabolism during infection is still limited. We aimed to carry out a comprehensive survey of the C. jejuni metabolic requirements to colonize the gut. In addition, we intend to explore the role of the resident microbiota in the modulation of C. jejuni metabolic requirements. Over the last decade, our laboratory has built considerable expertise in the study of C. jejuni and has made significant contributions to the understanding of its pathogenesis. We plan to leverage this expertise to address what we believe are among the most fundamental questions in C. jejuni biology, namely its metabolic requirements for effective host colonization and its interplay with the resident microbiota.

 描述（由申请方提供）：空肠弯曲菌是美国食源性腹泻的最常见原因。虽然它最常与自限性神经退行性疾病相关，但一小部分感染患者会发展出更严重的神经退行性并发症，称为格林-巴利综合征。尽管在该领域取得了许多重要进展，但对其致病机制仍知之甚少。C.空肠有能力有效地定殖于多种宿主的肠道，这使得该病原体能够进入食物链，从而对食品工业提出了重大挑战。因此，对C.空肠定殖提供了独特的机会，以获得关于病原体可以在其宿主的肠道中建立自身并成功地与驻留的微生物群竞争的机制的知识。确保营养物质和末端电子受体的呼吸链是核心的能力，病原体的殖民给定的生态位。虽然在模式生物微生物代谢的知识是大量的，少得多的是已知的代谢过程中感染。微生物病原体获取营养的多功能性正在成为它们在面对来自常驻微生物群的激烈竞争时定殖能力的核心。C.空肠的中枢代谢、它利用营养物质的能力以及它多样化的呼吸系统的几个方面已经建立。然而，这些研究主要是在培养基中进行的，因此对C。感染期间空肠的代谢仍然有限。本研究旨在对我国的C.空肠的代谢需求来定殖肠道。此外，我们还打算探索常驻微生物群在调节 C.空肠代谢要求。在过去的十年里，我们的实验室在C.并对其发病机制的了解做出了重大贡献。我们计划利用这些专业知识来解决我们认为是C语言中最基本的问题。空肠生物学，即其有效宿主定植的代谢要求及其与常驻微生物群的相互作用。

项目成果

Metabolic and fitness determinants for in vitro growth and intestinal colonization of the bacterial pathogen Campylobacter jejuni.

• DOI: 10.1371/journal.pbio.2001390
• 发表时间: 2017-05
• 期刊: PLoS biology
• 影响因子: 9.8
• 作者: Gao B;Vorwerk H;Huber C;Lara-Tejero M;Mohr J;Goodman AL;Eisenreich W;Galán JE;Hofreuter D
• 通讯作者: Hofreuter D