权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Characterization of the mechanisms underpinning quorum sensing progression in Pseudomonas aeruginosa

铜绿假单胞菌群体感应进展机制的表征

基本信息

批准号：
10726940
负责人：
Jon E Paczkowski
金额：
$ 5.61万
依托单位：
WADSWORTH CENTER
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：
2022-03-01 至 2027-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10726940
关键词：
Affect Affinity Anti-Bacterial Agents Architecture Bacteria Behavior Binding Biochemical Biological Assay Carrier Proteins Cell Communication Cell Cycle Cell Density Cell Signaling Process Cells ChIP-seq Clinical Communication Communities Complex DNA DNA Binding DNA Binding Domain Data Deoxyribonucleases Detection Development Down-Regulation Environment Enzymes Gene Expression Gene Expression Profile Genes Genetic Transcription Goals Growth High-Throughput Nucleotide Sequencing In Vitro Infection Ligands Light Maps Mediating Medicine Microbial Biofilms Molecular Molecular Conformation Mutagenesis Mutation Organism Output Pathogenesis Phase Play Process Production Proteins Pseudomonas aeruginosa Pseudomonas aeruginosa infection Regulation Regulatory Element Regulon Relaxation Reporter Repression Role Shapes Signal Transduction Signal Transduction Pathway Signaling Molecule Specificity Structure System Techniques Therapeutic Time Transcriptional Regulation Up-Regulation Virulence Virulence Factors X-Ray Crystallography combat cost experimental study extracellular genetic approach human pathogen in vivo insight metalloenzyme microbial community novel pathogenic bacteria prevent promoter protein folding protein protein interaction quorum sensing receptor receptor binding response rhamnolipid surfactant trait transcription factor transcriptome sequencing transmission process

项目摘要

PROJECT SUMMARY Quorum sensing (QS) is a mechanism of cell-cell communication that bacteria use to orchestrate collective behaviors, including virulence and biofilm formation. QS relies on the production, release, and group- wide detection of extracellular signal molecules called autoinducers (AI). QS allows bacteria to synchronously alter gene expression patterns that underpin collective behaviors, for example, biofilm formation. Some receptors bind and respond exclusively to one AI, while others bind and respond to multiple AIs. QS is responsible for releasing public goods that are beneficial to kin and, potentially, non-kin, and as a result, it plays an important role in shaping microbial community architecture. QS is now understood to be the norm in the bacterial world. Nonetheless, how different bacterial QS receptors initiate signal transduction is not understood. Defining the mechanisms that regulate QS-mediated production of public goods will be key for generally understanding how organisms coordinate community level changes in gene expression. This is particularly important in light of our findings that P. aeruginosa QS can be activated by signals produced by non-kin. Thus, determining the mechanisms that regulate QS progression after signal recognition will allow us to understand the respective benefits and drawbacks of strict versus relaxed ligand detection in QS-mediated communication. Bacteria live in heterogeneous communities and encounter mixtures of AIs produced by themselves, their kin, and their non-kin neighbors. Upon signal recognition, LasR and RhlR activate hundreds of genes, many of which are involved in pathogenesis and biofilm formation. While some signal transduction pathways follow a linear circuit, the QS system in P. aeruginosa is best described as a dense network of receptors and regulators with interconnecting regulatory systems and outputs. Canonically, the LasR-AI complex activates expression of rhlR and rhlI, thus launching the second QS system, enabling the two QS systems to function in tandem. Surprisingly, rhlR can be upregulated in clinical isolates containing lasR inactivating mutations. RhlR can also function without its partner synthase to regulate certain genes. This is achieved via a metallo-hydrolase known as PqsE. We discovered that PqsE and RhlR interact to form a complex. We will explore the role of PqsE in regulating RhlR function and describe their tandem role in transcriptional regulation and pathogenesis in AIM 1. The progression into QS corresponds to a downregulation of certain regulatory elements that function at low cell density to potentially mitigate early entry into QS. We have discovered that Fis, which is expressed during log phase, regulates the production of rhlA, a gene responsible for the synthesis of rhamnolipids, which are a bacterial surfactant important for infections. We will explore the mechanism Fis uses to achieve this regulation, in addition to what role it might play in regulating other QS genes and behaviors in AIM 2.

项目总结