Gene Expression Patterns and Lifestyles in Legionella

军团菌的基因表达模式和生活方式

基本信息

批准号：
7343210
负责人：
HOWARD A SHUMAN
金额：
$ 59.45万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-02-15 至 2010-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7343210
关键词：
Accounting Acute Alveolar Macrophages Antibiotics Bacteria Cells Communities Condition Data Development Disease Outbreaks Environment Evaluation Event Future Gene Expression Genes Genome Growth Hour Human Imagery Infection Intercistronic Region Knowledge L Cells Leg Legionella Legionella pneumophila Legionnaires&apos Disease Life Style Lung diseases Lysosomes Maps Microbial Biofilms Modeling Molecular Morphology Mus Mutation Nosocomial Infections Numbers Nutrient Open Reading Frames Organism Osmolar Concentration Pathway interactions Pattern Phagosomes Phase Physiological Plumbing Production Protozoa RNA Range Reporter Reporter Genes Research Personnel Resistance Reticulum Signal Transduction Source Staging Stress System Testing Thinking Time Vacuole axenic culture base biological adaptation to stress extracellular genome sequencing late endosome macrophage network models prevent programs research study sodium ion tool uptake

项目摘要

Legionella pneumophila, the gram-negative species that causes legionnaires' disease and other acute respiratory diseases, replicates within a wide range of phagocytic host cells. During legionnaires' disease, L. pneumophila replicates in alveolar macrophages. In the environment, it can replicate in an extraordinary range of protozoan hosts. Replication of L. pneumophila in protozoa is thought to occur in both planktonic and biofilm conditions. Biofilms are thought to be a primary source of the organism during outbreaks in both community-acquired and nosocomial infections. Little is known about the molecular basis for the ability of L. pneumophila to survive and multiply within such a wide range of environmental settings. Several investigators have proposed that L. pneumophila undergoes a developmental switch between distinct forms to account for the observed versatility in changing lifestyles. The availability of the complete L. pneumophila genome sequence and a microarray containing all known L. pneumophila genes, open reading frames and intergenic regions will permit the evaluation of several hypotheses that may account for these different physiologic states. In particular we propose to: (1) Test the hypothesis that distinct patterns of gene expression accompany discrete events during intracellular survival and growth of L. pneumophila; RNA from human macrophages will be isolated at various times after infection and the global pattern of Legionella gene expression will be determined using a whole genome Legionella microarray; (2)Test the hypothesis that distinct patterns of gene expression account for the observed phenotypic differences between axenically-grown and protozoan-grown L. pneumophila; RNA will be isolated from Legionella grown in protoza and the pattern of global gene expression will be compared to that of Legionella grown in axenic media as well as to Legionella that have been exposed to environmental stresses; (3) Test the hypothesis that specific patterns of gene expression in the presence of protozoan hosts promote the formation of Legionella-containing biofilms; RNA will be isolated from Legionella containing biofilms and the patterns of gene expression will be compared to the bacteria in the planktonic phase; (4) Develop model networks that describe relevant patterns of gene expression from the different conditions that have been examined to define specific reporters for each Legionella lifestyle or environmental condition.

嗜肺军团菌是一种导致军团病和其他急性呼吸道疾病的革兰氏阴性菌，可在多种吞噬宿主细胞内复制。在退伍军人病期间，嗜肺军团菌在肺泡巨噬细胞中复制。在环境中，它可以在大量原生动物宿主中复制。嗜肺军团菌在原生动物中的复制被认为发生在浮游和生物膜条件下。生物膜被认为是社区获得性感染和医院感染爆发期间微生物的主要来源。对于嗜肺军团菌在如此广泛的环境条件下生存和繁殖能力的分子基础知之甚少。一些研究人员提出，嗜肺军团菌经历了不同形式之间的发育转换解释了生活方式改变中观察到的多功能性。完整的嗜肺军团菌基因组序列和包含所有已知的嗜肺军团菌基因、开放阅读框和基因间区域的微阵列的可用性将允许评估可能解释这些不同生理状态的几种假设。我们特别建议：（1）检验以下假设：在嗜肺军团菌的细胞内存活和生长过程中，不同的基因表达模式伴随着离散事件；将在感染后的不同时间分离人类巨噬细胞的 RNA，并使用全基因组军团菌微阵列确定军团菌基因表达的整体模式； (2)检验假设不同的基因表达模式解释了在无菌生长和原生动物生长的嗜肺军团菌之间观察到的表型差异；将从原虫中生长的军团菌中分离出 RNA，并将全局基因表达模式与在无菌培养基中生长的军团菌以及暴露于环境胁迫的军团菌进行比较； (3) 检验原生动物宿主存在下基因表达的特定模式促进含军团菌生物膜形成的假设；将从含有生物膜的军团菌中分离出 RNA，并将基因表达模式与浮游阶段的细菌进行比较； (4) 开发模型网络，描述不同条件下基因表达的相关模式，这些模式已被检查以确定每种军团菌生活方式或环境条件的特定报告基因。