Using the Mycobacterium tuberculosis Genome to Predict Tuberculosis Pathology, Drug Resistance Acquisition and Identify Community Transmission Sites

使用结核分枝杆菌基因组预测结核病病理、耐药性获得和识别社区传播位点

基本信息

  • 批准号:
    10598532
  • 负责人:
  • 金额:
    $ 65.2万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-04-15 至 2025-03-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY Peru has the second highest incidence of tuberculosis (TB) disease in the Americas [1]. Despite causing the largest number of deaths worldwide due to any single agent infectious disease, no study has yet examined the influence of the pathogen genome on TB pathology as defined by the extent of radiological involvement on the chest radiograph. Therefore, our first Aim is to combine population level genome sequencing data with radiological data and linked clinical and demographic metadata to determine using novel multivariate genome wide association (GWAS) techniques the bacterial genomic biomarkers of TB pathology More than 80% of TB disease arises following a transmission event that occurs outside the home [2]. Understanding where, when and how frequently transmission events occur in the community is therefore critical in order to intervene and prevent spread of the disease. Identifying transmission sites, intervening and thereby preventing transmission is critical to diminishing the spread of primary drug resistance [3]. Therefore, our second Aim is to use population level whole genome sequencing together with real time GPS monitoring and the latest in spatial ecology mapping analysis to uncover new sites of TB transmission relative to matched controls Acquired drug resistance also contributes significantly to the global burden of drug resistance [4]. How TB strain genotype influences the acquisition of drug resistance remains disputed and insufficiently understood [5–11]. Identifying which genetic background is most associated with the acquisition of drug resistance to specific drugs would enable patients with drug susceptible TB to receive a personalized treatment regimen that minimizes the development of drug resistance on that genetic background. Therefore, our third aim is to use a unique set of >9000 bacterial strains collected in Peru at the population level over 20 years to phylogenetically infer which genetic background is associated with drug resistance acquisition; then confirm these findings in the laboratory and on a similar Moldovan dataset collection of >3000 strains. Preliminary studies have identified a TB bacterial genetic background that is highly associated with drug resistance [12]. We have also identified new community sites where significant TB transmission occurs [13] as well as identifying putative bacterial genetic polymorphisms independently associated with pathology in drug resistant TB. Our proposed study could help to diminish TB transmission in the region, identify new biomarkers of pathology, uncover new sites of TB transmission, and identify the bacterial genetic associations with drug resistance acquisition.
项目摘要 秘鲁是美洲结核病发病率第二高的国家[1]。尽管造成了 由于任何单一病原体传染病,全球死亡人数最多,但尚未有研究调查 病原体基因组对结核病病理学的影响,其定义为对结核病的放射性累及程度。 胸片。因此,我们的第一个目标是将联合收割机群体水平的基因组测序数据与 放射学数据和相关的临床和人口统计学元数据,以使用新的多变量基因组来确定 广泛关联(GWAS)技术,结核病病理学的细菌基因组生物标志物 超过80%的结核病是在家庭以外发生的传播事件后发生的[2]。 因此,了解社区中传播事件发生的地点、时间和频率至关重要 以干预和防止疾病的传播。确定传播部位,进行干预, 防止传播对减少原发性耐药性的传播至关重要[3]。因此,我们的第二 目的是利用群体水平的全基因组测序,结合真实的实时GPS监测和最新的 在空间生态学绘图分析中,发现与匹配对照相比的结核病传播新位点 获得性耐药性也是全球耐药性负担的重要组成部分[4]。结核菌株如何 基因型影响耐药性的获得仍然存在争议,而且认识不足[5-11]。 确定哪种遗传背景与获得对特定药物的耐药性最相关 将使药物敏感性结核病患者能够接受个性化的治疗方案, 在遗传背景上产生耐药性。因此,我们的第三个目标是使用一套独特的 在秘鲁收集了超过9000株细菌菌株,在20年的人口水平上, 遗传背景与耐药性获得相关;然后在实验室中确认这些发现 并且在>3000个菌株的类似的摩尔多瓦数据集集合上。 初步研究已经确定了与药物高度相关的结核病细菌遗传背景 阻力[12]。我们还确定了新的结核病严重传播的社区地点[13], 以及鉴定与药物中的病理学独立相关的推定细菌遗传多态性, 耐药结核病。我们提出的研究可能有助于减少该地区的结核病传播,确定新的生物标志物, 发现结核病传播的新位点,并确定细菌遗传与药物 电阻采集

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ 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 }}

ROBERT H GILMAN其他文献

UNDERSTANDING ALL-CAUSE MORTALITY AND COPD IN PERU: WHY SPIROMETRY SCREENING MATTERS FOR DIVERSE POPULATIONS
  • DOI:
    10.1016/j.chest.2022.08.1579
  • 发表时间:
    2022-10-01
  • 期刊:
  • 影响因子:
  • 作者:
    ERICA L CROSLEY;SHAKIR HOSSEN;ROBERT H GILMAN;J. JAIME MIRANDA;ANTONIO BERNABÉ-ORTIZ;ROBERT A WISE;WILLIAM CHECKLEY
  • 通讯作者:
    WILLIAM CHECKLEY

ROBERT H GILMAN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('ROBERT H GILMAN', 18)}}的其他基金

Infectious Diseases Training program in Bolivia: South-South Training with Peru
玻利维亚传染病培训项目:与秘鲁的南南培训
  • 批准号:
    10838920
  • 财政年份:
    2024
  • 资助金额:
    $ 65.2万
  • 项目类别:
Diagnostic Innovations for Pediatric Tuberculosis in Bolivia
玻利维亚儿童结核病的诊断创新
  • 批准号:
    10731855
  • 财政年份:
    2023
  • 资助金额:
    $ 65.2万
  • 项目类别:
Using the Mycobacterium tuberculosis Genome to Predict Tuberculosis Pathology, Drug Resistance Acquisition and Identify Community Transmission Sites
使用结核分枝杆菌基因组预测结核病病理、耐药性获得和识别社区传播位点
  • 批准号:
    10392356
  • 财政年份:
    2020
  • 资助金额:
    $ 65.2万
  • 项目类别:
Novel nanoparticular diagnostics for cerebral toxoplasmosis and Chagas in HIV patients living in Latin America
针对生活在拉丁美洲的艾滋病毒患者的脑弓形体病和恰加斯病的新型纳米诊断
  • 批准号:
    10405524
  • 财政年份:
    2018
  • 资助金额:
    $ 65.2万
  • 项目类别:
Novel nanoparticular diagnostics for cerebral toxoplasmosis and Chagas in HIV patients living in Latin America
针对生活在拉丁美洲的艾滋病毒患者的脑弓形体病和恰加斯病的新型纳米诊断
  • 批准号:
    10207356
  • 财政年份:
    2018
  • 资助金额:
    $ 65.2万
  • 项目类别:
Oxfendazole as a Broad Spectrum Deworming Medicine in Humans: Phase II Efficacy Study in Geohelminths
奥芬达唑作为人类广谱驱虫药:对土蠕虫的 II 期疗效研究
  • 批准号:
    9143283
  • 财政年份:
    2016
  • 资助金额:
    $ 65.2万
  • 项目类别:
Infectious Diseases Training program in Bolivia: South-South Training with Peru
玻利维亚传染病培训项目:与秘鲁的南南培训
  • 批准号:
    10580728
  • 财政年份:
    2015
  • 资助金额:
    $ 65.2万
  • 项目类别:
Infectious Diseases Training program in Bolivia: South-South Training with Peru
玻利维亚传染病培训项目:与秘鲁的南南培训
  • 批准号:
    10328561
  • 财政年份:
    2015
  • 资助金额:
    $ 65.2万
  • 项目类别:
Natural infection of norovirus and sapovirus in a birth cohort in a Peruvian periurban community
秘鲁城郊社区出生队列中诺如病毒和沙波病毒的自然感染
  • 批准号:
    8961698
  • 财政年份:
    2015
  • 资助金额:
    $ 65.2万
  • 项目类别:
Infectious Diseases Training program in Bolivia: South-South Training with Peru
玻利维亚传染病培训项目:与秘鲁的南南培训
  • 批准号:
    9065693
  • 财政年份:
    2015
  • 资助金额:
    $ 65.2万
  • 项目类别:

相似海外基金

Collaborative Research: Superinvaders: testing a general hypothesis of forest invasions by woody species across the Americas
合作研究:超级入侵者:测试美洲木本物种入侵森林的一般假设
  • 批准号:
    2331278
  • 财政年份:
    2024
  • 资助金额:
    $ 65.2万
  • 项目类别:
    Standard Grant
Collaborative Research: Intertropical Convergence Zone Variations from Stable Oxygen Isotope Tree-ring Records in the Tropical Americas
合作研究:热带美洲稳定氧同位素树轮记录的热带辐合带变化
  • 批准号:
    2303525
  • 财政年份:
    2024
  • 资助金额:
    $ 65.2万
  • 项目类别:
    Standard Grant
Collaborative Research: Superinvaders: testing a general hypothesis of forest invasions by woody species across the Americas
合作研究:超级入侵者:测试美洲木本物种入侵森林的一般假设
  • 批准号:
    2331277
  • 财政年份:
    2024
  • 资助金额:
    $ 65.2万
  • 项目类别:
    Standard Grant
Collaborative Research: Intertropical Convergence Zone Variations from Stable Oxygen Isotope Tree-ring Records in the Tropical Americas
合作研究:热带美洲稳定氧同位素树轮记录的热带辐合带变化
  • 批准号:
    2303524
  • 财政年份:
    2024
  • 资助金额:
    $ 65.2万
  • 项目类别:
    Standard Grant
Collaborative Research: Intertropical Convergence Zone Variations from Stable Oxygen Isotope Tree-ring Records in the Tropical Americas
合作研究:热带美洲稳定氧同位素树轮记录的热带辐合带变化
  • 批准号:
    2303526
  • 财政年份:
    2024
  • 资助金额:
    $ 65.2万
  • 项目类别:
    Standard Grant
Collaborative Research: Superinvaders: testing a general hypothesis of forest invasions by woody species across the Americas
合作研究:超级入侵者:测试美洲木本物种入侵森林的一般假设
  • 批准号:
    2331276
  • 财政年份:
    2024
  • 资助金额:
    $ 65.2万
  • 项目类别:
    Standard Grant
The Palestinian Americas: revolutionary struggle across the global south, 1950-1979
巴勒斯坦美洲:1950-1979 年全球南方的革命斗争
  • 批准号:
    AH/Y001214/1
  • 财政年份:
    2023
  • 资助金额:
    $ 65.2万
  • 项目类别:
    Fellowship
Immuno-epidemiological Approach in Tackling Emerging & Re-emerging Infections in the Tropical Americas
应对新兴疾病的免疫流行病学方法
  • 批准号:
    22KK0279
  • 财政年份:
    2023
  • 资助金额:
    $ 65.2万
  • 项目类别:
    Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))
DISES: Coevolutionary dynamics of humans and maize in the Americas
疾病:美洲人类和玉米的共同进化动态
  • 批准号:
    2307175
  • 财政年份:
    2023
  • 资助金额:
    $ 65.2万
  • 项目类别:
    Standard Grant
Conference: Reimagining Rights in the Americas
会议:重新构想美洲的权利
  • 批准号:
    2230329
  • 财政年份:
    2022
  • 资助金额:
    $ 65.2万
  • 项目类别:
    Standard Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了