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Decoding interspecies signaling networks and the biogeography of polymicrobial infections

解码种间信号网络和多种微生物感染的生物地理学

基本信息

批准号：
10809397
负责人：
Dominique Limoli
金额：
$ 21.58万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-18 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10809397
关键词：
3-Dimensional Address Anabolism Animal Model Antibiotic Therapy Antibiotics Attention Bacteria Bacterial Model Bacterial Physiology Behavior Biological Assay Cells Cessation of life Chemotaxis Chronic Communication Communities Data Disease Distant Ecology Environment Exposure to Flagella Fluorescent in Situ Hybridization Future Gastrointestinal tract structure Gene Expression Genes Genetic Genetic Screening Goals Hair Health Human Human body Image Imaging Techniques Immune Immune system In Situ In Vitro Individual Infection Investigation Laboratories Language Life Lung Lung Transplantation Lung infections Maps Measures Mediating Microbe Microbial Biofilms Molecular Biology Movement Nature Neighborhoods Nutrient Organ Organism Pathway interactions Patients Pattern Physiology Pilum Poison Population Positioning Attribute Proteins Pseudomonas aeruginosa Race Reporting Respiratory Tract Infections Role Sampling Sensory Signal Pathway Signal Transduction Signaling Molecule Site Staphylococcus aureus Structure Surface System Techniques Technology Therapeutic Three-Dimensional Imaging Tissues Viral Virulence Visualization Walking Wound Infection antibiotic tolerance antimicrobial appendage arm bacterial community cell motility chronic wound cystic fibrosis infection cystic fibrosis patients design extracellular genetic approach high throughput screening human disease human tissue implantable device in vivo in vivo Model insight interspecies communication live cell imaging member microbial microbial community next generation opportunistic pathogen pathogen polymicrobial biofilm respiratory social therapy design wound

项目摘要

PROJECT SUMMARY Polymicrobial communities are ubiquitous in the human body and their behaviors are critical drivers of both health and disease. Bacteria are social organisms; thus, the behavior of the group is driven not only by the composition of the community, but also by interactions between the constituents and their surrounding environment. A key principle shared among all communities, is that space matters. Groups organize to maximize acquisition of goods, minimize exposure to toxic compounds, and optimize communication. Our recent data reveal bacteria can communicate with members of distant species and respond by changing how they spatially structure their communities. My laboratory seeks to understand how bacteria communicate between species by observing them in their native environment, tracking their movements, and listening to and decoding their languages. We utilize Pseudomonas aeruginosa, the most notoriously problematic opportunistic pathogen in multiple types of polymicrobial infections, including chronic wounds and lung infections in cystic fibrosis (CF) patients. We recently reported that P. aeruginosa establishes infections with other important pathogens in the lungs of patients with CF for decades, remaining unresponsive to intense antibiotic therapies and causing lung decline and early death. In this proposal, we begin by visualizing the spatial landscape of polymicrobial communities in situ, in transplanted lungs from CF patients and animal models of polymicrobial infection. By combining next-generation tissue clearing and fluorescent in situ hybridization, we are able to visualize the spatial positioning of species on a range of spatial scales, in relation to each other and host structures. This will yield an unprecedented view of microbes during infection and provide a platform for visualizing communities in other organs rich in polymicrobial communities, such as the gastrointestinal tract. Next, we will systematically decode the interspecies signaling language. We designed high-throughput screens to identify genes necessary for signaling and the repertoire of signaling molecules. Using live-imaging techniques pioneered by my lab, we visualize and track the movement of bacterial cells, gene expression, and dynamics of motility appendages, upon modulation of the identified pathways. Initial studies reveal P. aeruginosa responds by activating multiple signaling systems, which tune the direction of movement and activate virulence systems. Collectively, these studies will construct a comprehensive picture of interspecies communication and enlighten how interactions exacerbate disease.

项目总结