Addressing genetic tractability and species-specific infection biology in Chlamydia pneumoniae
Addressing genetic tractability and species-specific infection biology in Chlamydia pneumoniae
批准号:
10571366
负责人:
KENNETH A FIELDS
金额:
$22.95万
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
项目状态:
已结题
起止时间:
2022-11-07 至 2024-10-31
关键词:
AccelerationAcuteAddressAllelesBiologyBronchitisCell SeparationCellsCellular biologyChlamydiaChlamydia trachomatisChlamydophila pneumoniaeCommunitiesComparative StudyComplementDataDevelopmentDiseaseEctopic ExpressionEndocytosisEngineeringEpithelial CellsEpitopesExhibitsFilopodiaFoundationsFutureGene DeletionGene DuplicationGene ExpressionGenesGeneticGenetic TechniquesGenitalGenitaliaHigh PrevalenceHumanInfectionInflammatoryInvadedLightMaintenanceMediatingMolecularMucous MembraneMutagenesisPathogenesisPathogenicityPhagocytesPhenotypePlasmidsPrevalenceProbabilityProcessProteinsRecruitment ActivityResearchRespiratory DiseaseRespiratory Tract InfectionsReverse engineeringRoleSinusitisSystemTechniquesTechnologyWorkcell typechronic infectioncommunity acquired pneumoniaconstitutive expressiondesignefficacy testingexpression vectorgene productgenetic manipulationhuman pathogeninducible gene expressionintracellular parasitismmembermutantnew technologynovel strategiesobligate intracellular parasitepathogenprotein functionreceptor mediated endocytosisrecruitrespiratory pathogenseropositivesorting nexinstissue tropismtraffickingvector
中文摘要
摘要
衣原体代表了一种理解成功的专性细胞内的范例
寄生。沙眼衣原体和肺炎衣原体都是人类的常见病原体,而沙眼衣原体和肺炎衣原体是人类常见的病原体。
肺炎呼吸道感染可能是最常见的。急性肺炎衣原体感染
表现为社区获得性肺炎、支气管炎和鼻窦炎,而其他
炎症性后遗症与慢性感染有关。遗传可控性研究进展
促进了沙眼衣原体致病机理的研究取得了长足的进展。
不幸的是,肺炎衣原体的类似研究进展滞后,导致缺乏细节。
关于感染的分子机制和排除利用信息的方法
比较研究。为了克服这一障碍,我们将设计使等位基因成为可能的质粒系统。
肺炎衣原体的替换和异位基因表达。这些新技术将成为
应用于原则证明研究,以解决由一对
肺炎克雷伯菌利用发散型III型分泌效应物操纵宿主细胞
生物学。在这些研究结束时,我们将建立新的方法,这将使我们受益
整个衣原体研究界,并促进对衣原体如何
物种进化是为了满足共同的发育需求。
英文摘要
ABSTRACT
Chlamydia species represent a paradigm for understanding successful obligate intracellular
parasitism. While C. trachomatis and C. pneumoniae are both prevalent human pathogens, C.
pneumoniae respiratory infections are likely most common. Acute C. pneumoniae infections
manifest as community acquired pneumonia, bronchitis, and sinusitis while additional
inflammatory sequelae are associated with chronic infection. Advances in genetic tractability
have facilitated considerable progress in characterizing C. trachomatis pathogenesis.
Unfortunately, similar progress has lagged for C. pneumoniae, leading to a paucity in details
regarding molecular mechanisms of infection and precluding informative approaches leveraging
comparative studies. To overcome this barrier, we will engineer plasmid systems enabling allelic
replacement and ectopic gene expression for C. pneumoniae. These new technologies will be
applied in proof-of-principle studies to address functional aspects manifested by a pair of
divergent type III secreted effectors employed by C. pneumoniae to manipulate host cell
biology. At the end of these studies, we will have established new approaches that will benefit
the entire Chlamydia research community and advance the understanding of how chlamydial
species have evolved to accomplish common developmental requirements.
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海外基金