Variation in M. tuberculosis in response to host selection

结核分枝杆菌对宿主选择的反应发生变化

基本信息

批准号：
7426989
负责人：
SARAH FORTUNE
金额：
$ 244.98万
依托单位：
HARVARD SCHOOL OF PUBLIC HEALTH
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-30 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7426989
关键词：
A 101 Acute Address Adenine Aerosols Affect Algorithms Alleles Animal Model Animals Antibiotics Antibodies Antigen-Presenting Cells Antigens Architecture Ascaridil Attenuated Automation Automobile Driving Bacteria Bacterial Antigens Bacterial Chromosomes Bacterial Infections Bacterial RNA Base Pairing Biology Blood capillaries CD8B1 gene Candidate Disease Gene Carrier Proteins Cell physiology Cells Cessation of life Characteristics Chemistry Chromosomes Chronic Clinical Clonality Collaborations Color Complement Complex Computer software Computers Condition Congenic Strain Coupled Cytosine Cytosol DNA DNA Damage DNA Methylation DNA Repair DNA Resequencing DNA Restriction Enzymes DNA Sequence Rearrangement Dam methyltransferase Data Depth Detection Development Dideoxy Chain Termination DNA Sequencing Disease Disease model Elements Engineering Environment Enzymes Epigenetic Process Epitopes Equipment Escherichia coli Essential Genes Eukaryota Eukaryotic Cell Event Experimental Models Family Fortune Foundations Freezing Frequencies Funding Mechanisms Future Gene Expression Gene Expression Regulation Gene Family Gene Frequency Gene Mutation Gene Structure Generations Genes Genetic Genetic Polymorphism Genetic Recombination Genetic Screening Genetic Variation Genets Genome Genomics Genus Mycobacterium Goals Growth Guanine HIV Haplotypes Heart Heterogeneity Holoenzymes Horizontal Gene Transfer Hour Human Hypoxia Immune Immune response Immune system Immunity Immunocompromised Host In Vitro Inbred C3H Mice Incubated Individual Infection Infection Control Inheritance Patterns Institutes Integration Host Factors Interferons Isotopes Label Laboratories LacZ Genes Length Libraries Life Literature Lung Macaca Maps Mass Spectrum Analysis Massachusetts Measurable Measures Mediating Mediator of activation protein Membrane Proteins Methodology Methods Methylation Methyltransferase Microarray Analysis Minor Modeling Modification Molecular Molecular Profiling Morphology Mus Mutate Mutation Mycobacterium bovis Mycobacterium smegmatis Mycobacterium tuberculosis Nature Nucleic Acids Numbers Oligonucleotide Microarrays Organ Organism Parents Pathogenesis Pattern Peptides Personal Communication Personal Satisfaction Pharmaceutical Preparations Phase Phenotype Pilot Projects Pilum Planet Mars Plasmids Play Polymerase Chain Reaction Polymorphism Analysis Population Price Process Prokaryotic Cells Protein Secretion Proteins Proteobacteria Proteome Proteomics Protocols documentation Publishing Purpose Pyelonephritis Rate Reading Regulation Regulon Relative (related person)Reporter Research Research Personnel Role Route Running Sampling Scientist Sequence Analysis Single Nucleotide Polymorphism Site Sorting - Cell Movement Speed Standards of Weights and Measures Stress Structure Structure of parenchyma of lung Surface Surface Antigens System T-Lymphocyte T-Lymphocyte Epitopes Technology Testing Time Tuberculosis Universities Uropathogenic E. coli Vaccines Variant Virulence Virulence Factors Virulent Week Work abstracting bacterial genetics base capillary cell type cost design design and construction epigenetic variation experience expression vector falls gene function genome sequencing homologous recombination in vivo innovation innovative technologies inorganic phosphate insertion/deletion mutation insight interest latent infection macrophage mecarzole medical schools microbial mouse model mutant mycobacterial new technology novel novel vaccines pathogen pressure promoter protein function research study response skills success tandem mass spectrometry therapeutic vaccine trend vaccine development vector

项目摘要

All pathogens that cause chronic infections must avoid clearance by the host immune response. Many have complex mechanisms to rapidly generate diversity in critical antigens. Mycobacterium tuberculosis chronically infects one third of the worlds' population and similarly must avoid clearance by the host immune system. However, there is currently little understanding of whether M. tuberculosis, like so many other pathogens, diversifies in vivo to escape host immune selection. In this proposal, we will test the hypothesis that M. tuberculosis varies, either genetically or epigenetically, during the course of infection and that this variation contributes to the ability of the bacteria to avoid clearance by the host immune response. We will use new genomics technologies—low cost genome sequencing and expression profiling—to systematically assess genetic and epigenetic variation in bacteria selected in a simple experimental model of disease chosen to create different immune pressures on the bacteria —mice of different MHC haplotypes. In these studies, we expect to provide fundamental insights into the mechanisms and targets of diversifying immune selection in M. tuberculosis.

所有引起慢性感染的病原体都必须避免被宿主免疫系统清除许多具有复杂的机制来快速产生关键抗原的多样性。结核分枝杆菌长期感染世界三分之一的人口同样必须避免被宿主免疫系统清除，但目前还很少。了解结核分枝杆菌是否像许多其他病原体一样在体内多样化在这个提议中，我们将检验 M. 结核病在感染过程中会在遗传或表观遗传上发生变化，并且这种变异有助于细菌避免被宿主免疫清除的能力我们将使用新的基因组学技术——低成本基因组测序和表达谱——系统评估细菌的遗传和表观遗传变异在简单的疾病实验模型中选择创建不同的免疫系统在这些研究中，我们预计细菌的压力——不同 MHC 单倍型的小鼠。为免疫多样化的机制和目标提供基本见解结核分枝杆菌的选择。