Decoding interspecies signaling networks and the biogeography of polymicrobial infections

解码种间信号网络和多种微生物感染的生物地理学

基本信息

  • 批准号:
    10809397
  • 负责人:
  • 金额:
    $ 21.58万
  • 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:
    2021-08-18 至 2026-06-30
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY Polymicrobial communities are ubiquitous in the human body and their behaviors are critical drivers of both health and disease. Bacteria are social organisms; thus, the behavior of the group is driven not only by the composition of the community, but also by interactions between the constituents and their surrounding environment. A key principle shared among all communities, is that space matters. Groups organize to maximize acquisition of goods, minimize exposure to toxic compounds, and optimize communication. Our recent data reveal bacteria can communicate with members of distant species and respond by changing how they spatially structure their communities. My laboratory seeks to understand how bacteria communicate between species by observing them in their native environment, tracking their movements, and listening to and decoding their languages. We utilize Pseudomonas aeruginosa, the most notoriously problematic opportunistic pathogen in multiple types of polymicrobial infections, including chronic wounds and lung infections in cystic fibrosis (CF) patients. We recently reported that P. aeruginosa establishes infections with other important pathogens in the lungs of patients with CF for decades, remaining unresponsive to intense antibiotic therapies and causing lung decline and early death. In this proposal, we begin by visualizing the spatial landscape of polymicrobial communities in situ, in transplanted lungs from CF patients and animal models of polymicrobial infection. By combining next-generation tissue clearing and fluorescent in situ hybridization, we are able to visualize the spatial positioning of species on a range of spatial scales, in relation to each other and host structures. This will yield an unprecedented view of microbes during infection and provide a platform for visualizing communities in other organs rich in polymicrobial communities, such as the gastrointestinal tract. Next, we will systematically decode the interspecies signaling language. We designed high-throughput screens to identify genes necessary for signaling and the repertoire of signaling molecules. Using live-imaging techniques pioneered by my lab, we visualize and track the movement of bacterial cells, gene expression, and dynamics of motility appendages, upon modulation of the identified pathways. Initial studies reveal P. aeruginosa responds by activating multiple signaling systems, which tune the direction of movement and activate virulence systems. Collectively, these studies will construct a comprehensive picture of interspecies communication and enlighten how interactions exacerbate disease.
项目总结

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Pseudomonas aeruginosa surface motility and invasion into competing communities enhances interspecies antagonism.
铜绿假单胞菌的表面运动和入侵竞争群落增强了种间拮抗作用。
  • DOI:
    10.1101/2024.04.03.588010
  • 发表时间:
    2024
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Sánchez-Peña,Andrea;Winans,JamesB;Nadell,CareyD;Limoli,DominiqueH
  • 通讯作者:
    Limoli,DominiqueH
The type IV pilus chemoreceptor PilJ controls chemotaxis of one bacterial species towards another.
IV 型菌毛化学感受器 PilJ 控制一种细菌物种对另一种细菌物种的趋化性。
  • DOI:
    10.1371/journal.pbio.3002488
  • 发表时间:
    2024
  • 期刊:
  • 影响因子:
    9.8
  • 作者:
    Yarrington,KaitlinD;Shendruk,TylerN;Limoli,DominiqueH
  • 通讯作者:
    Limoli,DominiqueH
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Dominique Limoli其他文献

Dominique Limoli的其他文献

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{{ truncateString('Dominique Limoli', 18)}}的其他基金

Decoding interspecies signaling networks and the biogeography of polymicrobial infections
解码种间信号网络和多种微生物感染的生物地理学
  • 批准号:
    10275234
  • 财政年份:
    2021
  • 资助金额:
    $ 21.58万
  • 项目类别:
Decoding interspecies signaling networks and the biogeography of polymicrobial infections
解码种间信号网络和多种微生物感染的生物地理学
  • 批准号:
    10649560
  • 财政年份:
    2021
  • 资助金额:
    $ 21.58万
  • 项目类别:
Decoding interspecies signaling networks and the biogeography of polymicrobial infections
解码种间信号网络和多种微生物感染的生物地理学
  • 批准号:
    10471287
  • 财政年份:
    2021
  • 资助金额:
    $ 21.58万
  • 项目类别:

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