Bacterial Genomic Diversity

细菌基因组多样性

基本信息

批准号：
8051660
负责人：
Michael Jacobs
金额：
$ 54.01万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-03-01 至 2014-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8051660
关键词：
Antibiotic Resistance Australia Award Bacteria Bacterial Genes Bacterial Genome Bacterial Infections Base Pairing Base Sequence Basic Science Behavior Biochemical Pathway Biological Warfare Biology Bioterrorism Burkholderia pseudomallei Cells Characteristics Child Clinic Clinical Collection Communicable Diseases Complex Computing Methodologies Coupling DNA Sequence Data Developing Countries Disease Disease Management Disease Outbreaks Drug resistance Dysentery Emergency Situation Emerging Communicable Diseases Environment Epidemic Epidemiology Escherichia coli Escherichia coli O157 Event Food Poisoning Forensic Medicine Francisella tularensis Generations Genes Genetic Genetic Variation Genome Genomic Islands Genomics Genotype Goals Gram-Negative Bacteria Health Host Defense Human Immune In Vitro Individual Infection Intervention Investigation Knowledge Laboratories Life Light Melioidosis Methods Molecular Molecular Evolution Molecular Genetics Mutation Natural Immunity Nucleotides Pacific Northwest Pathogenesis Phenotype Play Population Pseudomonas aeruginosa Public Health Research Research Design Research Personnel Resistance Resolution Role Sampling Shapes Shigella dysenteriae Single Nucleotide Polymorphism Source Southeastern Asia Speed Spinach - dietary Staging Technology Testing Therapeutic United States Variant Work Yersinia pestis antimicrobial antimicrobial drug base biodefense experience genome sequencing improved indexing interest mortality novel novel strategies pathogen pressure product development programs response tool trend

Antibiotic Resistance Australia Award Bacteria Bacterial Genes Bacterial Genome Bacterial Infections Base Pairing Base Sequence Basic Science Behavior Biochemical Pathway Biological Warfare Biology Bioterrorism Burkholderia pseudomallei Cells Characteristics Child Clinic Clinical Collection Communicable Diseases Complex Computing Methodologies Coupling DNA Sequence Data Developing Countries Disease Disease Management Disease Outbreaks Drug resistance Dysentery Emergency Situation Emerging Communicable Diseases Environment Epidemic Epidemiology Escherichia coli Escherichia coli O157 Event Food Poisoning Forensic Medicine Francisella tularensis Generations Genes Genetic Genetic Variation Genome Genomic Islands Genomics Genotype Goals Gram-Negative Bacteria Health Host Defense Human Immune In Vitro Individual Infection Intervention Investigation Knowledge Laboratories Life Light Melioidosis Methods Molecular Molecular Evolution Molecular Genetics Mutation Natural Immunity Nucleotides Pacific Northwest Pathogenesis Phenotype Play Population Pseudomonas aeruginosa Public Health Research Research Design Research Personnel Resistance Resolution Role Sampling Shapes Shigella dysenteriae Single Nucleotide Polymorphism Source Southeastern Asia Speed Spinach - dietary Staging Technology Testing Therapeutic United States Variant Work Yersinia pestis antimicrobial antimicrobial drug base biodefense experience genome sequencing improved indexing interest mortality novel novel strategies pathogen pressure product development programs response tool trend

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项目摘要

The proposed work will explore the genetic basis for real-world variability in the behavior of human pathogens during infections of individual humans and whole populations. The focus will be on two gramnegative pathogens, Burkholderia pseudomallei and Shigella dysenteriae, both of which cause infectious diseases associated with substantial mortality in humans. B. pseudomallei is an opportunistic pathogen that causes melioidosis, a disease largely found in Southeast Asia and Northern Australia; it has been classified as a select agent because of its perceived potential as a biowarfare agent. S. dysenteriae causes dysentery epidemics, predominantly in developing countries, which cause substantial mortality, particular in children. The basic hypothesis behind the proposed work is that genetic changes occurring during individual B. pseudomallei infections or during S. dysenteriae epidemics will reveal the selective pressures operating on these species as a result of host defenses, treatment, and¿in the case of S. dysenteriae¿the dynamic changes in the characteristics of the host population within which the epidemic is spreading. A better understanding of the molecular basis for these genetic effects may suggest new approaches to the clinical and public-health management of the diseases. The project has a major technical component since, although new-generation-sequencing technology is opening up the opportunity for studies of the type proposed, key aspects of the technology remain underdeveloped. We place particular emphasis on improvements in the rapidity with which new base-pair-accurate, finished genome sequences can be produced for the index strains of particular infections or epidemics. These reference sequences play a key in role in the experimental and computational methods used to detect the genetic changes that occur during infections and epidemics.

拟议的工作将探索人类行为中现实世界变异性的遗传基础病原体在人类和整个人群的感染过程中。重点将放在两个革新法上病原体，Burkholderia pseudomallei和Shigella dysenteriae，两者都引起感染力与人类大量死亡有关的疾病。 B.假alle骨是一种机会性病原体引起Melioidosis，这是一种在东南亚和澳大利亚北部大部分发现的疾病；它已被分类作为精选代理，由于其视为生物脂肪剂的潜力。 S.痢疾会导致痢疾发作，主要在发展中国家，这会导致重大死亡率，尤其是儿童。提出的工作背后的基本假设是，单个B期间发生的遗传变化。假单胞菌感染或在S. s. s. s. dysenteriae发作期间将揭示在运行的选择性压力这些物种是宿主防御，治疗和尚体链球菌的结果流行病在其中的宿主人群特征的变化。更好对这些遗传作用的分子基础的理解可能表明临床的新方法和疾病的公共卫生管理。此后，该项目具有主要的技术组成部分尽管新成立的序列技术正在为研究类型的研究提供了机会提议的，该技术的关键方面仍然不发达。我们特别强调新的碱基准确性，成品基因组序列的速度改善可以是为特定感染或发作的指数菌株产生。这些参考序列播放键在用于检测遗传变化的实验和计算方法中的作用感染和流行病。