Cooperative roles of FHA and ACT in Bordetella virulence
FHA 和 ACT 在博德特氏菌毒力中的合作作用
基本信息
- 批准号:10541178
- 负责人:
- 金额:$ 53.61万
- 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:2021-01-20 至 2025-12-31
- 项目状态:未结题
- 来源:
- 关键词:Acellular VaccinesAdenylate Cyclase ToxinAdherenceAdolescent and Young AdultAffectAnimal ModelBacteriaBacterial AdhesinsBindingBiochemicalBiologicalBiological AssayBordetellaBordetella Virulence FactorsBordetella bronchisepticaBordetella pertussisC-terminalCell Culture TechniquesCell surfaceCellsChildhoodDeveloped CountriesDevelopmentDiseaseEpithelial CellsEventFamilyGeneticGoalsHemagglutininHumanImmunityImmunizeInfantInfectionInflammationInflammatory ResponseLipoprotein (a)Lower respiratory tract structureMacrophage-1 AntigenMaintenanceMammalian CellMammalsMediatingModelingMolecularMusPeptide HydrolasesPertussisPertussis VaccinePhagocytesPlayProtein SecretionProteinsRattusRespiratory Tract InfectionsRiskRoleSeriesSignal TransductionSurfaceSystemTestingTherapeuticToxinVaccinationVaccinesVirulenceVirulence FactorsWorkexperimental studyinsightmembernovel vaccinespathogenperiplasmpreventprotein functionreceptorresponsetransmission process
项目摘要
Summary/Abstract
Pertussis (aka whooping cough) is re-emerging in developed countries despite high vaccine coverage.
Resurgence is due primarily to waning immunity to the causal bacterium Bordetella pertussis (Bp) in adolescents
and young adults immunized with acellular (aP) pertussis vaccines. Moreover, while aP vaccination protects
against disease, at least initially, it does not protect against colonization or prevent transmission, which puts
infants, who are most vulnerable to serious and sometimes fatal disease, at greater risk. New vaccines that
protect against both colonization and disease are needed. Their development requires a better understanding of
the molecular mechanisms underlying Bp virulence.
A strictly human-adapted pathogen, Bp is extremely closely related to Bordetella bronchiseptica (Bb),
which infects nearly all mammals. Bp and Bb produce a nearly identical set of virulence factors, some of which,
including filamentous hemagglutinin (FHA) and adenylate cyclase toxin (ACT), are functionally
interchangeable. FHA is a critical adhesin, a component of acellular vaccines, and the prototypical member of
the Two Partner Secretion (TPS) family. Using Bb and its natural hosts (rats and mice), we showed that in
addition to mediating adherence to host cells, FHA plays important roles in controlling the initial inflammatory
response to infection and in mediating defense of the bacteria against clearance by phagocytic cells, which
contributes to persistence in the lower respiratory tract (LRT). Our work on the mechanism of secretion and
processing of the “precursor” FhaB protein to FHA has led to major advances in the mechanism of two partner
secretion, and we showed that FhaB itself, rather than FHA, is critical for bacterial persistence in the LRT. ACT
also contributes to bacterial persistence in the LRT by mediating defense against phagocytic cell clearance.
We and others have shown that ACT binds to FhaB/FHA on the bacterial surface. We propose a model in
which ACT, while bound to FhaB on the bacterial surface, binds to CR3 on phagocytic cells, triggering
degradation of the C-terminal, periplasmically-located, FhaB prodomain, resulting in efficient delivery of ACT to
phagocytic cells and not to epithelial cells. We propose to: 1) Investigate the roles of DegP, CtpA, EnvC and
LbcA in regulated degradation of the FhaB prodomain, 2) Investigate the relationship between ACT binding to
CR3, regulated degradation of the FhaB prodomain, and delivery of ACT specifically to phagocytic cells, and 3)
Investigate the consequences of dysregulated FhaB prodomain degradation on the establishment and
maintenance of respiratory infection.
摘要/文摘
项目成果
期刊论文数量(0)
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Peggy A Cotter其他文献
The Comparison of Single Serum Antibody Values Against B. pertussis, C. pneumoniae, and M. pneumoniae Antigens in Active Duty American Soldiers in Korea Who Had Prolonged Cough Illnesses (Cases) with Similar Antibody Values in Sera from Well Active Duty Soldiers in Hawaii (Controls)
- DOI:
10.1203/00006450-199904020-01051 - 发表时间:
1999-04-01 - 期刊:
- 影响因子:3.100
- 作者:
Judy M Vincent;William F Nauschwetz;Andrew Lipton;Craig M Ono;Cory N Costello;Lori Kelsey;Gunther Hsue;Lisa A Jackson;Raffi Tachdjian;Peggy A Cotter;Jeffrey A Gornbein;James D Cherry - 通讯作者:
James D Cherry
Peggy A Cotter的其他文献
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{{ truncateString('Peggy A Cotter', 18)}}的其他基金
Cooperative roles of FHA and ACT in Bordetella virulence
FHA 和 ACT 在博德特氏菌毒力中的合作作用
- 批准号:
10206412 - 财政年份:2021
- 资助金额:
$ 53.61万 - 项目类别:
Cooperative roles of FHA and ACT in Bordetella virulence
FHA 和 ACT 在博德特氏菌毒力中的合作作用
- 批准号:
10331076 - 财政年份:2021
- 资助金额:
$ 53.61万 - 项目类别:
Contact-dependent signaling and DNA transposition in Burkholderia
伯克霍尔德氏菌中的接触依赖性信号传导和 DNA 转座
- 批准号:
10610358 - 财政年份:2020
- 资助金额:
$ 53.61万 - 项目类别:
Contact-dependent signaling and DNA transposition in Burkholderia
伯克霍尔德氏菌中的接触依赖性信号传导和 DNA 转座
- 批准号:
10381490 - 财政年份:2020
- 资助金额:
$ 53.61万 - 项目类别:
PlrSR-dependent Signal Transduction in Bordetella Virulence
博德特氏菌毒力中 PlrSR 依赖性信号转导
- 批准号:
10097965 - 财政年份:2017
- 资助金额:
$ 53.61万 - 项目类别:
Contact-Dependent Signaling in Burkholderia
伯克霍尔德杆菌中的接触依赖性信号传导
- 批准号:
9321389 - 财政年份:2016
- 资助金额:
$ 53.61万 - 项目类别:
Contact-Dependent Signaling in Burkholderia
伯克霍尔德杆菌中的接触依赖性信号传导
- 批准号:
9197358 - 财政年份:2016
- 资助金额:
$ 53.61万 - 项目类别:
BcpAIOB-Mediated CDI and Biofilm Formation in Burkholderia pseudomallei
BcpAIOB 介导的鼻疽伯克霍尔德氏菌中的 CDI 和生物膜形成
- 批准号:
8750147 - 财政年份:2014
- 资助金额:
$ 53.61万 - 项目类别:
Microbial Pathogenesis: Mechanisms of Infectious Disease
微生物发病机制:传染病的机制
- 批准号:
8200143 - 财政年份:2011
- 资助金额:
$ 53.61万 - 项目类别:
Function and Secretion of Bordetella Filamentous Hemagglutinin
博德特氏菌丝状血凝素的功能和分泌
- 批准号:
8245274 - 财政年份:2011
- 资助金额:
$ 53.61万 - 项目类别:
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