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The Genomics and Antagonism of Pathobiont Colonization

致病生物定植的基因组学和拮抗作用

基本信息

批准号：
10160780
负责人：
ANTHONY W MARESSO
金额：
$ 73.67万
依托单位：
BAYLOR COLLEGE OF MEDICINE
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：
2019-04-15 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10160780
关键词：
Address Adherence Adhesives Alleles Antibiotic Resistance Apical Back Bacteria Bacterial Adhesins Bacterial Proteins Biological Models Biopsy Blood Clinical Communicable Diseases Communities Complement Digestion Drug resistance Ecosystem Elements Enteral Enterobacteriaceae Enterococcus Enterococcus faecalis Enterococcus faecium Epidemiology Epithelial Escherichia coli Event Family Gastrointestinal tract structure Gene Expression Profile Gene Proteins Genes Genomics Health Human Immune response Infection Intestinal Mucosa Intestines Klebsiella pneumoniae Knowledge Laboratories Large Intestine Lead Libraries Maps Medical center Medicine Microbe Modeling Molecular Movement Mucous Membrane Multi-Drug Resistance Nosocomial Infections Nutrient Organ Organism Pathogenesis Pathogenicity Phase Population Predisposition Property Research Personnel Rest Role Sampling Sepsis Shapes Small Intestines Source Superbug Surface Therapeutic Tissue Engineering Vaccines Virulence Factors Virulent college colonization resistance commensal bacteria drug development drug resistant bacteria experimental study fitness genetic approach genetic element genetic variant gut microbiota host microbiome immune function member microbiota mucosal vaccine new therapeutic target novel pandemic disease pathobiont pathogen pathogenic bacteria prevent reference genome response reverse genetics tool transcriptome transmission process user-friendly

项目摘要

Project Summary The human intestine is an ecosystem of microbes. This ecosystem helps shape immune function, provides scarce nutrients, aids in digestion, and when balanced, maintains health. Amongst the many bacteria that colonize this organ, some harbor virulence factors and carry drug-resistance, the so-called pathobionts, which may be asymptomatic members of the intestinal microbiota. Under certain conditions, mostly related to a loss of immune function, these organisms can cause systemic bloodstream infections that can lead to sepsis or sepsis-like states. As such, they are leading causes of community and nosocomial infections. The most prominent of these are members of the superfamily of Enterobacteriaceae and Enterococcaceae. The most concerning pathobiont members of the Enterobacteriaceae are the Gram-negatives Eschericia coli and Klebsiella pneumoniae, while those of the Enterococcaceae include the Gram- positive Enterococcus faecalis and Enterocccus faecium. There are no vaccines for these species. The focus of this project is to generate the world's first fully annotated and searchable reference library of pathogenic and drug-resistant pathobionts that colonize the human intestine. This library will then be the source of intra-species competition in organotypic models of the human intestine to select for the most fit binders and colonizers of the apical mucosa. These strains then be assessed for their ability to breach the mucosa (translocation), induce global gene expression across a hundred different human lines, and be out-competed or antagonized by members of a small and large intestine commensal community. At the completion of the project, there will be numerous bacterial, host, and commensal targets for new drug development.

项目总结