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（由适用提供）：空肠弯曲杆菌是美国出生腹泻的最常见原因。尽管它通常与自限性的腹泻病有关，但一小部分感染患者会出现更严重的神经差异并发症，称为Guillain-Barré综合征。尽管该领域取得了许多重要的进步，但对其致病性机制知之甚少。 C. jejuni有能力有效地殖民各种宿主的肠子，这使该病原体能够进入食物链，从而向食品工业面临重大挑战。因此，对空肠梭菌的研究提供了独特的机会，以获取有关病原体可以在其宿主的肠道轨道中建立自己的机制并成功与居民微生物群竞争的机制的知识。确保其呼吸链的营养和末端电子受体对病原体定居的能力至关重要。尽管模型生物中微生物代谢的知识是实质的，但对感染过程中的代谢知之甚少。微生物病原体获取营养的多功能性是其在居民微生物群体中脱离钢铁竞争的能力的中心。已建立了空肠梭菌中央代谢的许多基本参数，其利用营养的能力以及其多样化的呼吸下巴的几个方面。但是，这些研究在很大程度上是在培养基中进行的，因此在感染过程中对空肠梭菌代谢的理解仍然有限。我们的目的是对肠道梭菌代谢要求进行全面调查，以殖民肠道。此外，我们打算探讨居民微生物群在调制中的作用 C.空肠代谢要求。在过去的十年中，我们的实验室在J. Jejuni的研究中建立了考虑专家，并为理解其发病机理做出了重大贡献。我们计划利用这项专家来解决我们认为是乔朱尼生物学中最基本的问题之一，即其代谢要求有效宿主殖民及其与居民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