Type IV Protein Secretion in Helicobacter pylori
幽门螺杆菌中 IV 型蛋白的分泌
基本信息
- 批准号:10390377
- 负责人:
- 金额:$ 71.49万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-02-18 至 2026-03-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAnimal ModelAntibiotic ResistanceAntibioticsArchitectureBacteriaBiological AssayCancer EtiologyCarcinogensCell Culture TechniquesCellsCessation of lifeChromosome MappingChronicClarithromycinClinicalComplexCryoelectron MicroscopyDNADiseaseDuodenal UlcerElementsEventExhibitsFundingGastric AdenocarcinomaGastric lymphomaGastric mucosaGastric ulcerGene ExpressionGenesGenetic TechniquesGoalsGram-Negative BacteriaHelicobacter InfectionsHelicobacter pyloriHelicobacter pylori induced gastric cancerHomologous GeneHumanIncidenceIndividualInfectionKnowledgeLeadLifeLinkMalignant - descriptorMapsMembraneMethodsMicrobeModelingMolecularMucositisN-terminalNucleotidesOncoproteinsOrganismOutcomePathogenicity IslandPathologicPeptic UlcerPersonsPhenotypeProtein SecretionProteinsResearchResistanceResolutionRhizobium radiobacterRisk FactorsRoleSignal TransductionStomachStomach DiseasesStructural ModelsStructureStructure-Activity RelationshipSymptomsSystemTestingTimeType IV Secretion System PathwayVariantVirulence FactorsWorkWorld Health Organizationalpha helixbasecarcinogenesisfitnessgenetic manipulationimprovedin vivomalignant stomach neoplasmmutantparticleperiplasmpersistent bacteriaprototyperecruitresponse
项目摘要
PROJECT SUMMARY (ABSTRACT)
Helicobacter pylori is a Gram-negative bacterium that colonizes the human stomach. H. pylori colonization of the
stomach results in chronic gastric mucosal inflammation and is a strong risk factor for gastric cancer and
duodenal or gastric ulceration. Gastric cancer is the third leading cause of cancer-related death worldwide, and
H. pylori has been classified as a type I carcinogen by the World Health Organization. The H. pylori CagA protein
is secreted through a type IV secretion system (T4SS), enters gastric cells, and causes alterations in cellular
signaling associated with malignant transformation. CagA and components of the Cag T4SS are encoded by
genes within a chromosomal region known as the cag pathogenicity island (PAI), which is present in some H.
pylori strains but not others. The incidence of symptomatic gastroduodenal disease (gastric cancer or peptic
ulceration) is higher among individuals infected with cag PAI-positive strains than among those infected with cag
PAI-negative strains. The molecular architecture and protein composition of the H. pylori Cag T4SS differ
substantially from corresponding features of T4SSs found in other bacterial species. The overarching long-term
goal of this research is to develop a better understanding of the molecular mechanisms by which H. pylori causes
gastric disease. During the previous funding period, we isolated a transmembrane core complex of the Cag
T4SS containing five proteins encoded by the cag PAI, described three main structural features of the complex
(outer membrane cap, periplasmic ring and stalk), and built partial models of three proteins within the complex.
The aims of the current proposal are i) to build a complete structural model of the five Cag T4SS core complex
components; ii) to define structure-function relationships for CagY (a core complex component predicted to span
from the inner membrane to the outer membrane), elucidating its role in CagA recruitment and T4SS activity;
and (iii) to define actions of the Cag T4SS in vivo. Methods will include single particle cryo-electron microscopy
analysis of the T4SS core complex, specialized techniques for genetic manipulation of H. pylori, cell culture-
based assays of Cag T4SS activity, and an animal model of H. pylori-induced gastric cancer. These studies will
provide important advances in our understanding of the molecular mechanisms by which H. pylori infection can
lead to gastric cancer and other gastric diseases. On a broader scope, these studies will increase our
understanding of bacterial secretion systems and the delivery of bacterial virulence factors into host cells, as
well as molecular mechanisms underlying microbe-induced carcinogenesis.
项目总结(摘要)
项目成果
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{{ truncateString('TIMOTHY L COVER', 18)}}的其他基金
Type IV Protein Secretion in Helicobacter pylori
幽门螺杆菌中 IV 型蛋白的分泌
- 批准号:
10595676 - 财政年份:2016
- 资助金额:
$ 71.49万 - 项目类别:
Type IV Protein Secretion in Helicobacter pylori
幽门螺杆菌中 IV 型蛋白的分泌
- 批准号:
10218960 - 财政年份:2016
- 资助金额:
$ 71.49万 - 项目类别:
Helicobacter pylori cag Pathogenicity Island and Gastric Carcinogenesis
幽门螺杆菌致病岛与胃癌发生
- 批准号:
8413059 - 财政年份:2013
- 资助金额:
$ 71.49万 - 项目类别:
Regulation of H. Pylori Virulance by Dietary Factors that Impact Gastric Cancer
影响胃癌的饮食因素对幽门螺杆菌毒力的调节
- 批准号:
9274163 - 财政年份:2009
- 资助金额:
$ 71.49万 - 项目类别:
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