Mechanisms of Corynebacterium-Dolosigranulum Interactions that Shape Human Nasal Microbiota

棒状杆菌与多洛西颗粒相互作用塑造人类鼻腔微生物群的机制

基本信息

  • 批准号:
    10378695
  • 负责人:
  • 金额:
    $ 40万
  • 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:
    2021-04-01 至 2026-03-31
  • 项目状态:
    未结题

项目摘要

The objective unifying our two areas of NIGMS-funded research is to identify molecular mechanisms underlying microbe-microbe and microbe-host interactions involving D. pigrum and nasal Corynebacterium species that shape the human nasal microbiota. Evidence indicates that Corynebacterium species and Dolosigranulum pigrum play key roles in structuring a nasal microbiota beneficial to human health. For example, people with high levels of Corynebacterium and/or D. pigrum in their nasal microbiota are less likely to be colonized by pathobionts and, therefore, are at lower risk of invasive infections in other parts of their bodies. Similarly, nasal microbiota dominated by Corynebacterium/D. pigrum are often associated with health rather than with diseases such as otitis media and pneumonia. Our overarching hypothesis is that interactions between D. pigrum and Corynebacterium species drive a beneficial health-promoting human nasal microbiota. A central goal of this research is to shift from correlations in compositional data to causation by identifying molecular mechanisms that underlie both in vivo associations and in vitro phenotypes. Our NIGMS-supported preliminary data show that there are four common species of nasal Corynebacterium. Three of these are positively correlated with D. pigrum and enhance D. pigrum growth in vitro. Furthermore, cocultivation of D. pigrum with Corynebacterium pseudodiphtheriticum together robustly inhibits S. pneumoniae in vitro, compared to either alone. D. pigrum also inhibits S. aureus growth in vitro. These in vitro results support a role for in vivo interactions with potential health benefits. To understand microbe-microbe and microbe-epithelium interactions in the human nasal passages, we will use human nasal epithelial organoids at an air-liquid interface (aka nasanoids) as an innovative biomimetic model system in collaboration with our Organoid Core. Microbial communities are characterized by a network of metabolic interactions among microbes and with the environment. Genomic analysis uncovered D. pigrum auxotrophies indicating it depends on the host or microbial neighbors for key nutrients. Our research will address gaps in understanding the food web that supports human nasal microbiota; the effects on the epithelium of hosting microbes; and the physiology and function of potentially beneficial nasal bacteria. A key advantage of using human nasal microbiota to identify metabolic interactions is that it is a self-contained bacterial-epithelial system with regard to nutrients. We will use complementary approaches including pan-genomics, metabolic modeling, dual bacteria-epithelium transcriptomics, metabolomics and genetic engineering. We will also tackle key technical challenges in the nasal microbiome field to facilitate identification of metabolites, proteins and genes involved in interactions. To advance research on D. pigrum and nasal Corynebacterium, we have established a large culture collection of nasal bacteria from > 400 volunteers of all ages. By identifying metabolic interactions between nasal Corynebacterium species, D. pigrum, and the nasal epithelium that sculpt a health- promoting human nasal microbiota, we hope to catalyze new approaches for preventing infection.
统一nigms资助的两个研究领域的目标是确定潜在的分子机制

项目成果

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Katherine Paige Lemon其他文献

Katherine Paige Lemon的其他文献

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{{ truncateString('Katherine Paige Lemon', 18)}}的其他基金

Nasal Microbial Consortia Combat Antibiotic-Resistant Bacteria
鼻腔微生物联盟对抗抗生素耐药性细菌
  • 批准号:
    10357970
  • 财政年份:
    2021
  • 资助金额:
    $ 40万
  • 项目类别:
Nasal Microbial Consortia Combat Antibiotic-Resistant Bacteria
鼻腔微生物联盟对抗抗生素耐药性细菌
  • 批准号:
    10583470
  • 财政年份:
    2021
  • 资助金额:
    $ 40万
  • 项目类别:
Mechanisms of Corynebacterium-Dolosigranulum Interactions that Shape Human Nasal Microbiota
棒状杆菌与多洛西颗粒相互作用塑造人类鼻腔微生物群的机制
  • 批准号:
    10205817
  • 财政年份:
    2021
  • 资助金额:
    $ 40万
  • 项目类别:
Mechanisms of Corynebacterium-Dolosigranulum Interactions that Shape Human Nasal Microbiota
棒状杆菌与多洛西颗粒相互作用塑造人类鼻腔微生物群的机制
  • 批准号:
    10606509
  • 财政年份:
    2021
  • 资助金额:
    $ 40万
  • 项目类别:
Impact of Commensal Corynebacterium Species on Pathogen Colonization and Microbiota Composition
共生棒状杆菌物种对病原体定植和微生物群组成的影响
  • 批准号:
    10081046
  • 财政年份:
    2016
  • 资助金额:
    $ 40万
  • 项目类别:
Impact of commensal Corynebacterium species on pathogen colonization and microbiota composition
共生棒杆菌属对病原体定植和微生物群组成的影响
  • 批准号:
    9006947
  • 财政年份:
    2016
  • 资助金额:
    $ 40万
  • 项目类别:
Biofilm Formation by Listeria monocytogenes
单核细胞增生李斯特菌形成生物膜
  • 批准号:
    7130587
  • 财政年份:
    2006
  • 资助金额:
    $ 40万
  • 项目类别:
Biofilm Formation by Listeria monocytogenes
单核细胞增生李斯特菌形成生物膜
  • 批准号:
    7236233
  • 财政年份:
    2006
  • 资助金额:
    $ 40万
  • 项目类别:
Biofilm Formation by Listeria monocytogenes
单核细胞增生李斯特菌形成生物膜
  • 批准号:
    7408120
  • 财政年份:
    2006
  • 资助金额:
    $ 40万
  • 项目类别:

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激素治疗、绝经年龄、既往产次和 APOE 基因型会影响老年人的认知。
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