Chemical Biological Discovery of Lipid Virulence Factors in the Major Bacterial Pathogens
主要细菌病原体中脂质毒力因子的化学生物学发现
基本信息
- 批准号:10518252
- 负责人:
- 金额:$ 64.25万
- 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:2022-06-22 至 2027-05-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAutophagocytosisBacteriaBacterial ChromosomesBiologicalBiological ProcessBiologyCatalogsCell modelCellsCellular AssayChemical StructureChemicalsChromosome MappingCommunicable DiseasesCord FactorsDataDatabasesDetectionDevelopmentDiagnosisDiseaseEnteralEnvironmentEvolutionFeedbackFoamy MacrophageFunctional disorderGene DeletionGenerationsGenesGenomicsGenus MycobacteriumGram-Negative BacteriaHourHumanImmune responseImmunologic ReceptorsInfectionInfectious Diseases ResearchLaboratoriesLinkLipidsLiteratureLocationLysosomesMapsMass Spectrum AnalysisMeasuresMediatingMembraneMethodsModernizationMolecularMusMycobacterium tuberculosisNamesNatureNucleosidesNutrientOrganismPatientsPhenotypePhospholipidsProcessProductionProteinsProteomicsRoleSalmonellaSalmonella entericaSalmonella typhiScienceSignal TransductionStudy SectionSystemT cell responseTestingTranscriptVirulenceVirulence FactorsVirulentWhole Organismbasecomparativecomparative genomicsexperienceexperimental studyforward geneticsgene discoverygene functiongenetic approachin vivoinhibitorinsightlipidomelipidomicsmacrophagemetabolomicsmycobacterialnovel strategiesoverexpressionpathogenpathogenic bacteriaprenylreceptorresponsereverse geneticsselective expressionsuccesstooltranscriptomicstranslational study
项目摘要
Project Summary
Chemical Biological Discovery of Lipid Virulence Factors in the Major Bacterial Pathogens
For decades, the search for the causes of bacterial virulence has focused on genes rather than metabolites.
Genetic approaches have been broadly successful, and modern infectious disease research relies
fundamentally on genomic maps of the major pathogens. Owing to the lack of whole-organism chemical
biology tools, bacterial lipids have not been systematically tested for their roles in virulence, even though lipids
are the primary interface with the human host, where they control nutrient flow and trigger host immune
response. We invented a mass spectrometry platform for lipid profiling to detect nearly all ionizable lipids in a
bacterial cell within 2 hours. Experiments on Mycobacterium tuberculosis and Salmonella enterica serovar
Typhi now provide clear evidence for the general insight that many, perhaps the majority, of lipids in the world's
bacterial pathogens, are currently unknown as named compounds. Based on successes in identifying virulence
factors in two major pathogens of worldwide significance, we will carry out a chemical biology approach known
as forward lipidomics. Specifically, we will use whole organism mass spectrometry profiling to discover the
lipids that are selectively expressed in virulent bacteria and are unknown in existing lipid catalogs. Then, we
will chemically synthesize the virulence associated lipids and link them to their biosynthetic genes for deletion
in bacteria using reverse genetic approaches. Using genetically modified bacteria that are deficient in defined
lipids, we will determine the roles of virulence lipids during infection. Using nature identical synthetic lipids, we
will determine the cellular mechanisms of generation of foamy macrophages and identify immune receptors
that mediate host response. We will create lipid maps of the major Gram negative pathogen groups based on
patient strains to build the overlooked field of chemical biology of bacterial virulence. These basic and
translational studies will support the development new forward lipidomics approaches to the diagnosis and
treatment of major infectious diseases.
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
DAVID Branch MOODY其他文献
DAVID Branch MOODY的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('DAVID Branch MOODY', 18)}}的其他基金
Chemical Biological Discovery of Lipid Virulence Factors in the Major Bacterial Pathogens
主要细菌病原体中脂质毒力因子的化学生物学发现
- 批准号:
10651853 - 财政年份:2022
- 资助金额:
$ 64.25万 - 项目类别:
Study of M. tuberculosis under human host selection to identify virulence and barrier lipids (Project 1)
研究人类宿主选择下的结核分枝杆菌以确定毒力和屏障脂质(项目 1)
- 批准号:
10612035 - 财政年份:2021
- 资助金额:
$ 64.25万 - 项目类别:
Metabolic adaptions of Mycobacterium tuberculosis at diverse host-pathogen interfaces
结核分枝杆菌在不同宿主-病原体界面的代谢适应
- 批准号:
10630740 - 财政年份:2021
- 资助金额:
$ 64.25万 - 项目类别:
Metabolic determinants of Mtb virulence, vulnerability and variation
结核分枝杆菌毒力、脆弱性和变异的代谢决定因素
- 批准号:
10438911 - 财政年份:2021
- 资助金额:
$ 64.25万 - 项目类别: