Deciphering molecular mechanisms underlying vertical transmission of Listeria monocytogenes
破译单增李斯特菌垂直传播的分子机制
基本信息
- 批准号:10664028
- 负责人:
- 金额:$ 5.27万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-08-20 至 2024-12-20
- 项目状态:已结题
- 来源:
- 关键词:5&apos Untranslated RegionsAbscessAdultAffinityAmino AcidsBacteriaBehaviorBindingBloodCardiacCell WallCellsClinicalCommunicable DiseasesDataDiagnosisDiseaseElderlyEnvironmentExhibitsFetal DeathFetal TissuesFetusFlow CytometryFluorescence MicroscopyFrequenciesGastroenteritisGeneral PopulationGeneticGenetic VariationGoalsHIV SeropositivityHealthHealth BenefitHeartImmune responseImmune signalingImmunityImmunocompromised HostImmunohistochemistryIn Situ HybridizationIndividualInfectionInflammatoryInlB proteinInvadedKnowledgeLife StyleListeria monocytogenesListeriosisMammalian CellMembrane ProteinsModelingMolecularMorbidity - disease rateMothersMusNatureNeonatalNucleotidesOrganOrganismOutcomeOutcome StudyPathogenesisPathologyPatientsPersonsPhenotypePlacentaPredispositionPregnancy ComplicationsPregnancy lossPregnant WomenProductionPublic HealthReceptor SignalingRibosomesSeveritiesSignal TransductionSurfaceTranscriptTranslationsTropismVariantVertical TransmissionVirulence Factorsabortioncell typecytokinedesignexperienceexperimental studyfetalfetal infectionfetal lossfoodbornefoodborne pathogengut colonizationimmune activationimprovedinfection riskinsightintestinal epitheliumknowledgebasemodel organismmortalitynovelpathogenplacental infectionposttranscriptionalpregnantpreventprotein expressionprotein functionreceptor bindingtooltransmission process
项目摘要
Abstract
Pregnant women are more likely to be infected with the intracellular pathogen Listeria monocytogenes (Lm) than the general population, and the bacterium can be vertically transmitted leading to fetal infection and pregnancy loss. Despite its public/health/relevance, the determinants of maternofetal transmission remain undefined. Examination of clinical Lm isolates indicates that subpopulations of strains possess an enhanced ability for vertical transmission. One of these strains, 07PF0776, was first noted for its ability to target the heart, and this cardiotropism requires InlB, a bacterial surface protein known to be important for the invasion of mammalian cells. Experimental evidence indicates that InlB is similarly required for vertical transmission and that high InlB expression alone is sufficient to significantly enhance vertical transmission in an unrelated strain. The goal for this project is to elucidate the mechanisms by which InlB enhances the vertical transmission of hypervirulent Lm strains and of Lm generally. The project aims are designed to connect strain-specific genetic variations to altered bacterial behavior, host pathology, and immune responses. The current working hypothesis is that enhanced translation of inlB occurs in Lm hypervirulent subpopulations as the result of a trinucleotide substitution in the 5’ untranslated region (UTR) of the inlB transcript that promotes ribosome binding. It is also hypothesized that amino acid variations within InlB enhance InlB binding to the bacterial cell wall and thus increase InlB surface abundance. Aim 1 will determine how InlB levels are altered in 07PF0776 by looking at InlB synthesis, degradation, and cell wall affinity. This aim will also explore how the 5’ UTR contributes to increased protein expression. Aim 2 will determine how increased InlB expression promotes bacterial colonization of the placenta and fetus. Experiments will use pregnant mice as a model and compare strains with varying levels of InlB activity. Fluorescence microscopy combined with immuno-histochemistry will determine if InlB-high-expressing strains have enhanced invasion of specific placental cell types, or alternatively gain access through new portals of entry. RNAScope in situ hybridization and flow cytometry will establish how bacterial localization impacts the nature of the placental immune response. The ultimate goal of the above aims will be to establish the mechanisms by which strains of Lm cause severe fetal and neonatal disease. These studies may eventually allow for improved treatment of severe Lm infection and more effective strategies to protect pregnant women from Lm-induced pregnancy complications.
摘要
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Crossing the Barrier: A Comparative Study of Listeria monocytogenes and Treponema pallidum in Placental Invasion.
- DOI:10.3390/cells13010088
- 发表时间:2023-12-31
- 期刊:
- 影响因子:6
- 作者:
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Samuel Eallonardo其他文献
Samuel Eallonardo的其他文献
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{{ truncateString('Samuel Eallonardo', 18)}}的其他基金
Deciphering molecular mechanisms underlying vertical transmission of Listeria monocytogenes
破译单增李斯特菌垂直传播的分子机制
- 批准号:
10314192 - 财政年份:2021
- 资助金额:
$ 5.27万 - 项目类别:
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