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:
- 金额:$ 5.61万
- 依托单位:
- 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:
- 关键词:AffectAffinityAnti-Bacterial AgentsArchitectureBacteriaBehaviorBindingBiochemicalBiological AssayCarrier ProteinsCell CommunicationCell CycleCell DensityCell Signaling ProcessCellsChIP-seqClinicalCommunicationCommunitiesComplexDNADNA BindingDNA Binding DomainDataDeoxyribonucleasesDetectionDevelopmentDown-RegulationEnvironmentEnzymesGene ExpressionGene Expression ProfileGenesGenetic TranscriptionGoalsGrowthHigh-Throughput Nucleotide SequencingIn VitroInfectionLigandsLightMapsMediatingMedicineMicrobial BiofilmsMolecularMolecular ConformationMutagenesisMutationOrganismOutputPathogenesisPhasePlayProcessProductionProteinsPseudomonas aeruginosaPseudomonas aeruginosa infectionRegulationRegulatory ElementRegulonRelaxationReporterRepressionRoleShapesSignal TransductionSignal Transduction PathwaySignaling MoleculeSpecificityStructureSystemTechniquesTherapeuticTimeTranscriptional RegulationUp-RegulationVirulenceVirulence FactorsX-Ray Crystallographycombatcostexperimental studyextracellulargenetic approachhuman pathogenin vivoinsightmetalloenzymemicrobial communitynovelpathogenic bacteriapreventpromoterprotein foldingprotein protein interactionquorum sensingreceptorreceptor bindingresponserhamnolipidsurfactanttraittranscription factortranscriptome sequencingtransmission 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
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Jon E Paczkowski其他文献
Jon E Paczkowski的其他文献
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{{ truncateString('Jon E Paczkowski', 18)}}的其他基金
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
- 批准号:
10642512 - 财政年份:2022
- 资助金额:
$ 5.61万 - 项目类别:
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
- 批准号:
10574607 - 财政年份:2022
- 资助金额:
$ 5.61万 - 项目类别:
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
- 批准号:
10337557 - 财政年份:2022
- 资助金额:
$ 5.61万 - 项目类别:
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
- 批准号:
10797300 - 财政年份:2022
- 资助金额:
$ 5.61万 - 项目类别:
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