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Mechanisms of interaction between bacteriophage and their hosts throughout the infection cycle

整个感染周期中噬菌体与其宿主之间的相互作用机制

基本信息

批准号：
10644004
负责人：
Sarah M Doore
金额：
$ 35.39万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-06-13 至 2027-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10644004
关键词：
Address Affect Affinity Antibiotic Resistance Bacteria Bacterial Infections Bacteriophages Binding Binding Proteins Biochemical Biological Biological Assay Biological Models Biological Process Biology Capsid Cells Cessation of life Characteristics Citrobacter freundii Clinic Clinical Clustered Regularly Interspaced Short Palindromic Repeats Collaborations Combating Antibiotic Resistant Bacteria Communicable Diseases Complication Cryo-electron tomography Cryoelectron Microscopy Data Data Analyses Data Set Developing Countries Diarrhea Disease Dysentery Engineering Enteral Environment Escherichia coli Etiology Evolution Florida Food Functional disorder Gastrointestinal tract structure Gene Expression Gene Expression Regulation Genes Genetic Genetic Transcription Genome Geometry Goals Gram-Negative Bacteria Health Human Human body In Vitro Industrialization Infection Kinetics Knock-out Lipopolysaccharides Location Lytic Mass Spectrum Analysis Measures Medical Membrane Proteins Michigan Mission Modeling Multicenter Studies Mutagenesis National Institute of Allergy and Infectious Disease Organism Outcome Pathway interactions Phage Receptors Planets Preventive therapy Preventive treatment Production Property Protein Analysis Proteins RNA Sequences Research Resolution Risk Salmonella enterica Series Serotyping Shigella Shigella Infections Shigella flexneri Specificity Stress Structure Surface System Tail Techniques Tertiary Protein Structure Testing Time Transfer RNA Universities Viral Virus Water Work World Health Organization antibiotic resistant infections combat crosslink experimental study fitness gel electrophoresis genetic analysis gut bacteria imaging modality in vivo innovation interest knock-down mortality mutant next generation sequencing novel novel therapeutics opportunistic pathogen particle pathogen pathogenic bacteria receptor recruit ribosome profiling transcriptome sequencing

项目摘要

Bacterial viruses, known as bacteriophages or phages, are among the most abundant biological entities on the planet. These viruses vary broadly in terms of genome content, infection mechanisms, replication cycles, and structure. With an increasing interest in using bacteriophages to combat antibiotic resistant bacteria, it is necessary to understand mechanisms of how these viruses infect their hosts; replicate and regulate both their genes and their hosts’ genes; and how they persist in various environments, including the human body and/or storage conditions. However, our current model systems inherently only represent a fraction of bacteriophage diversity. The long-term goal of this work is to develop an additional bacteriophage system—the Moogleviruses— that appear to be ubiquitous in the environment and clinically useful qualities. They have, however, only recently been isolated because they do not commonly infect the model species of bacteria Escherichia coli and Salmonella enterica. Instead, these viruses are often isolated against the pathogenic bacteria Shigella flexneri or opportunistic pathogens such as Citrobacter freundii. Because these viruses are obligately lytic and specific to one of the most common etiological agents of diarrhea, S. flexneri, they could be used for controlling this species of bacteria in food or water, or for treating antibiotic-resistant infections. At this time, however, we lack sufficient understanding of their biological processes. Moogleviruses have distinct characteristics versus other bacteriophages, including a semi-specific host range, a large number of tRNAs encoded in their genomes, and uncommon capsid and genome sizes. The central hypothesis of this work is that these viruses use alternative strategies to infect and persist compared to more thoroughly characterized model systems. The objectives of this specific proposal are therefore to determine the mechanisms Shigella-infecting Moogleviruses use to identify their hosts, modulate the expression of viral and host genes on a translational level, and assemble into new particles that can persist in the environment. The expected outcomes of this proposal are: 1) the identification of critical interacting regions between the phage receptor-binding proteins and both primary and secondary receptors on the S. flexneri host, along with determining the kinetics of attachment and entry; 2) complete Ribo- seq and RNA-seq datasets from a variety of environments and infection conditions, leading to a mechanistic understanding of how phage infection alters translational efficiency of phage and host genes; and 3) a broadly resolved assembly pathway of the Mooglevirus capsid, with an indication of proteins or protein domains responsible for affecting capsid stability. This work will have impacts for both basic biology, expanding our repertoire of known bacteriophage strategies and mechanisms for infection and persistence; and medical application, informing how these phages themselves could be applied to combat S. flexneri infections in the clinic, or how their properties could be used to engineer novel phages for medical or industrial applications.

细菌病毒，被称为噬菌体或噬菌体，是地球上最丰富的生物实体之一