Evolutionary multispecies transcriptomics to reveal genes conferring pathogenicity within Leptospira spp
进化多物种转录组学揭示钩端螺旋体致病性基因
基本信息
- 批准号:10448321
- 负责人:
- 金额:$ 20.94万
- 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:2021-07-09 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:Acute Renal Failure with Renal Papillary NecrosisAdherenceAdhesionsAffectAnimalsAwarenessBacteriaBayesian NetworkBiologicalBiological AssayBiological ProcessBiologyCellsCenters for Disease Control and Prevention (U.S.)CharacteristicsComplexCountryDestinationsDeveloped CountriesDevelopmentDiagnosticDisastersDiseaseDisease OutbreaksEarly DiagnosisEmerging Communicable DiseasesEnvironmentEpidemiologyEssential GenesEventEvolutionFresh WaterFutureGene ExpressionGene Expression ProfileGenesGeneticGenetic TranscriptionGrantHealthHematogenousHemorrhageHumanHurricaneImpairmentIn VitroIndividualInfectionInvestigationKnowledgeLeptospiraLeptospirosisLibrariesLifeLife Cycle StagesLungMeasuresMethodsMilitary PersonnelMolecularMorbidity - disease rateMucous MembraneNatural HistoryOrder SpirochaetalesOrganOrganismPathogenesisPathogenicityPhenotypePhylogenetic AnalysisPopulationPreventionPrevention approachProcessProteinsPublic HealthPuerto RicoResource-limited settingResourcesRoleSlumSoilSourceSportsSwimmingSyndromeSystemTestingUnited States National Institutes of HealthVirulenceWaterZoonosesadhesion processbasebiological adaptation to stressbiological systemsburden of illnesscandidate identificationcomparativedesigndifferential expressiondisorder preventionfarmergene functiongene interactiongenome-wideimprovedin vitro Assayin vitro Modelin vivoinner cityinnovationinsightmortalitymutantneglectpathogenresponsetooltranscriptomicstransmission processvaccine development
项目摘要
PROJECT SUMMARY
Leptospirosis is an emerging infectious disease and the leading zoonotic cause of morbidity and mortality
worldwide, with its greatest burden on subsistence farmers and urban slum populations. Leptospirosis causes life-
threatening disease and has emerged as a major cause worldwide of pulmonary hemorrhage syndrome (LPHS)
and acute kidney injury. To date, there is no effective prevention and control for leptospirosis in resource-poor
settings. In the US and other industrialized countries, leptospirosis is a major cause of disease among inner-city
populations, military personnel, and individuals engaged in swimming and water sports. Leptospirosis is caused by
environmentally transmitted spirochetes belonging to more than 300 serovars among seventeen pathogenic
species within the genus Leptospira, a genus that also comprises 26 non-pathogenic species and 21 intermediate
species, the latter with undefined role as disease causative agent. The hallmark of infection with Leptospira species
is its rapid hematogenous dissemination after the organism penetrates through mucous membranes, disseminating
to multiple organs throughout the host. Despite the sizable burden of disease associated with leptospirosis, the
biological and genetic mechanisms of pathogenesis associated with Leptospira remain poorly understood. This
crucial gap of knowledge has impaired the development of better diagnostic and control tools. In this exploratory
proposal, we hypothesize that shifts in gene expression, together with divergent and convergent evolution of gene
function, have led to diversity in ability of Leptospira to survive and thrive outside of the host and facultative
pathogenicity. To identify genes responsible for pathogenicity, we will use a comparative systems biological
approach, in which we profile transcription across species using in vitro models of infection that are in vivo
surrogates for gene expression. Those in vitro models mimic the epidemiological life cycle of the bacteria and the
biological processes essential to establish disease. Through access to our extensive library of himar1-based
mutants, we will identify strains with gene disruption for some of those targets. Through known functional
phenotypes using well-characterized in vitro assays of adherence and translocation, as well as ability to survive
and thrive in environmental matrices such as water and soil, we will determine and characterize the role of those
genes in pathogenicity and transmission. Acquiring knowledge of the identity of genes responsible for pathogenicity
and transmission is a major priority for the molecular understanding of the mechanisms of leptospiral pathogenesis
that will directly facilitate the advance of public health measures through the development of improved diagnostic
and prevention methods.
项目总结
钩端螺旋体病是一种新出现的传染病,是导致发病率和死亡率的主要人畜共患病原因。
在世界范围内,自给自足的农民和城市贫民窟人口承受着最大的负担。钩端螺旋体病导致生命-
具有威胁性的疾病,已成为世界范围内肺出血综合征(LPHS)的主要原因
和急性肾损伤。到目前为止,在资源贫乏地区尚无有效预防和控制钩端螺旋体病的方法。
设置。在美国和其他工业化国家,钩端螺旋体病是市中心疾病的主要原因
从事游泳和水上运动的人群、军事人员和个人。钩端螺旋体病是由
环境传播的螺旋体属于17个致病菌中的300多个血清型
钩端螺旋体属内的种,该属还包括26个非致病种和21个中间体
物种,后者具有不明的致病因素作用。钩端螺旋体感染的特征
它是在生物体穿过粘膜后迅速的血源性传播,传播
到宿主体内的多个器官。尽管与钩端螺旋体病相关的疾病负担相当大,但
钩端螺旋体致病的生物学和遗传学机制尚不清楚。这
知识的严重差距阻碍了更好的诊断和控制工具的开发。在这个探索性的
建议,我们假设基因表达的转变,以及基因的发散和趋同进化
功能,导致钩端螺旋体在寄主和兼性之外生存和繁衍的能力不同
致病性。为了鉴定致病基因,我们将使用比较系统生物学
方法,其中我们使用体内感染的体外模型来描述跨物种的转录
基因表达的代用品。这些体外模型模拟了细菌的流行病学生命周期和
建立疾病所必需的生物过程。通过访问我们基于HIMAR1的广泛库
突变株,我们将为其中一些目标鉴定基因中断的菌株。通过已知的功能
使用体外黏附和易位以及存活能力的良好表征的表型分析
并在水和土壤等环境基质中茁壮成长,我们将确定和表征这些环境基质的作用
致病性和传播性基因。获取致病相关基因身份的知识
而传播是理解钩端螺旋体致病机制的主要分子基础
这将通过开发改进的诊断方法直接促进公共卫生措施的进展
和预防方法。
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)
MPL36, a major plasminogen (PLG) receptor in pathogenic Leptospira, has an essential role during infection.
- DOI:10.1371/journal.ppat.1011313
- 发表时间:2023-07
- 期刊:
- 影响因子:6.7
- 作者:
- 通讯作者:
{{
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 }}
Jeffrey Peter Townsend其他文献
Jeffrey Peter Townsend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('Jeffrey Peter Townsend', 18)}}的其他基金
Evolutionary multispecies transcriptomics to reveal genes conferring pathogenicity within Leptospira spp
进化多物种转录组学揭示钩端螺旋体致病性基因
- 批准号:
10283483 - 财政年份:2021
- 资助金额:
$ 20.94万 - 项目类别:
相似海外基金
An innovative, AI-driven prehabilitation platform that increases adherence, enhances post-treatment outcomes by at least 50%, and provides cost savings of 95%.
%20创新、%20AI驱动%20康复%20平台%20%20增加%20依从性、%20增强%20治疗后%20结果%20by%20at%20至少%2050%、%20和%20提供%20成本%20节省%20of%2095%
- 批准号:
10057526 - 财政年份:2023
- 资助金额:
$ 20.94万 - 项目类别:
Grant for R&D
Improving Repositioning Adherence in Home Care: Supporting Pressure Injury Care and Prevention
提高家庭护理中的重新定位依从性:支持压力损伤护理和预防
- 批准号:
490105 - 财政年份:2023
- 资助金额:
$ 20.94万 - 项目类别:
Operating Grants
I-Corps: Medication Adherence System
I-Corps:药物依从性系统
- 批准号:
2325465 - 财政年份:2023
- 资助金额:
$ 20.94万 - 项目类别:
Standard Grant
Unintrusive Pediatric Logging Orthotic Adherence Device: UPLOAD
非侵入式儿科记录矫形器粘附装置:上传
- 批准号:
10821172 - 财政年份:2023
- 资助金额:
$ 20.94万 - 项目类别:
Nuestro Sueno: Cultural Adaptation of a Couples Intervention to Improve PAP Adherence and Sleep Health Among Latino Couples with Implications for Alzheimer’s Disease Risk
Nuestro Sueno:夫妻干预措施的文化适应,以改善拉丁裔夫妇的 PAP 依从性和睡眠健康,对阿尔茨海默病风险产生影响
- 批准号:
10766947 - 财政年份:2023
- 资助金额:
$ 20.94万 - 项目类别:
CO-LEADER: Intervention to Improve Patient-Provider Communication and Medication Adherence among Patients with Systemic Lupus Erythematosus
共同领导者:改善系统性红斑狼疮患者的医患沟通和药物依从性的干预措施
- 批准号:
10772887 - 财政年份:2023
- 资助金额:
$ 20.94万 - 项目类别:
Pharmacy-led Transitions of Care Intervention to Address System-Level Barriers and Improve Medication Adherence in Socioeconomically Disadvantaged Populations
药房主导的护理干预转型,以解决系统层面的障碍并提高社会经济弱势群体的药物依从性
- 批准号:
10594350 - 财政年份:2023
- 资助金额:
$ 20.94万 - 项目类别:
Antiretroviral therapy adherence and exploratory proteomics in virally suppressed people with HIV and stroke
病毒抑制的艾滋病毒和中风患者的抗逆转录病毒治疗依从性和探索性蛋白质组学
- 批准号:
10748465 - 财政年份:2023
- 资助金额:
$ 20.94万 - 项目类别:
Improving medication adherence and disease control for patients with multimorbidity: the role of price transparency tools
提高多病患者的药物依从性和疾病控制:价格透明度工具的作用
- 批准号:
10591441 - 财政年份:2023
- 资助金额:
$ 20.94万 - 项目类别:
Development and implementation of peer-facilitated decision-making and referral support to increase uptake and adherence to HIV pre-exposure prophylaxis in African Caribbean and Black communities in Ontario
制定和实施同行协助决策和转介支持,以提高非洲加勒比地区和安大略省黑人社区对艾滋病毒暴露前预防的接受和依从性
- 批准号:
491109 - 财政年份:2023
- 资助金额:
$ 20.94万 - 项目类别:
Fellowship Programs