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：
7173850
负责人：
HOWARD A SHUMAN
金额：
$ 58.84万
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/7173850
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.

肺炎军团菌是引起军团疾病和其他急性呼吸道疾病的革兰氏阴性物种，在广泛的吞噬宿主细胞内复制。在军团疾病中，肺炎乳杆菌在肺泡巨噬细胞中复制。在环境中，它可以在特殊的原生动物宿主中复制。原生动物中肺炎乳杆菌的复制被认为是在浮游物和生物膜条件下发生的。在社区获得和医学院感染中，生物膜被认为是爆发过程中生物体的主要来源。关于肺炎乳杆菌在如此广泛的环境环境中生存和繁殖能力的分子基础知之甚少。一些研究人员提出，肺炎乳杆菌在不同形式之间经历了发展说明了改变生活方式的多功能性。完整的肺炎乳杆菌基因组序列和包含所有已知肺炎乳杆菌基因，开放式阅读框和基因间区域的微阵列的可用性将允许评估几种可能解释这些不同生理状态的假设。特别是我们建议：（1）检验以下假设：基因表达的不同模式伴随着细胞内存活和肺炎乳杆菌生长的离散事件；感染后的不同时间将分离来自人类巨噬细胞的RNA，使用整个基因组军团菌微阵列确定军团菌基因表达的全局模式。（2）检验以下假设基因表达的不同模式解释了轴杆生长和原生动物生长的肺乳杆菌之间观察到的表型差异。 RNA将从原生沙中生长的军团菌中分离出来，将全球基因表达的模式与在轴突培养基中生长的军团菌以及已暴露于环境应力的军团菌中的军团菌的模式进行比较；（3）检验以下假设：在原生动物宿主存在下基因表达的特定模式促进了含有军团菌的生物膜的形成； RNA将从含有生物膜的军团菌中分离出来，并将基因表达的模式与浮游阶段的细菌进行比较。（4）开发模型网络，这些网络描述了已经检查的不同条件的基因表达模式，这些模式已被检查，这些条件已被检查，以定义每个军团菌生活方式或环境条件的特定记者。