Project 2: Leveraging Metagenomics of the Microbiome to predict colonization/infection by antimicrobial-resistant pathogens

项目 2:利用微生物组的宏基因组学来预测耐药病原体的定植/感染

基本信息

项目摘要

ABSTRACT Leveraging Metagenomics of the Microbiome to Predict Colonization/Infection by Antimicrobial- Resistant Pathogens (Project #2) Antimicrobial resistance is a growing, global threat to public health. Vancomycin-resistant enterococci (VRE), extended spectrum β-lactamase producing/carbapenem-resistant Enterobacteriaceae (ESBL-E/CRE) and Clostridiodes difficile are key antimicrobial resistant (AMR) pathogens that share the intestine as the initial site of colonization. Therefore, colonization resistance provided by the commensal microbiota of the intestines is a critical aspect of the pathophysiology of these organisms. The completion of the initial stages of the Human Microbiome Project has provided new understanding of how the microbiome impacts infections and has generated novel tools for further advances in this critical area of human health. Additionally, unbiased approaches to bacterial identification have resulted in increasing appreciation that VRE, ESBL-E/CRE, and C. difficile often co-colonize patients suggesting that these organisms are interacting with each other in addition to the commensal microflora. The long term goals of this project, in synergy with other portions of this P01 proposal, are to dissect the mechanisms underlying how interactions among the commensal microflora, the host, and VRE, ESBL-E/CRE, and C. difficile impact intestinal colonization and subsequent infection by these AMR pathogens. Although it is well known that microbiome disruption by antimicrobials is a key initial step in colonization by these pathogens, we seek to address the key knowledge gap of why only a subset of patients receiving antimicrobials become colonized and eventually infected by these organisms. To this end, we propose performing longitudinal studies of intensive care unit and hematopoietic stem cell transplant patients at two distinct hospitals in the Texas Medical Center. Patients will be classified depending on both initial and longitudinal colonization status, and these classifications will be correlated with metagenomics based microbiome analyses of serial stool samples. In concert with computational biologists, the metagenomics data will be mined for particularly species or combinations of species that are either protective against or positively associated with colonization and infection, including co-colonization. Additionally, we will test whether samples from the clinical cohort can protect mice from AMR pathogen challenge to validate associations observed clinically. Finally, we will also use animal models to test how pre-existing colonization with a particular organism under study impacts subsequent colonization by a distinct AMR pathogen. By synergizing with microbiota experts, computational biologists, and physician-scientists from the highly integrated Gulf Coast Consortium on Antimicrobial Resistance, this proposal seeks to sharpen understanding of how critical AMR pathogens colonize and infect humans in order to provide a critical platform for novel preventive or therapeutic approaches to mitigate the AMR scourge.
摘要

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)

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SAMUEL A SHELBURNE其他文献

SAMUEL A SHELBURNE的其他文献

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{{ truncateString('SAMUEL A SHELBURNE', 18)}}的其他基金

Role of β-lactamase encoding gene amplification in the development of non-carbapenemase producing, carbapenem-resistant Enterobacteriaceae
β-内酰胺酶编码基因扩增在产生非碳青霉烯酶、耐碳青霉烯肠杆菌科细菌中的作用
  • 批准号:
    10373951
  • 财政年份:
    2021
  • 资助金额:
    $ 55.34万
  • 项目类别:
Impact of regulatory cross-talk on the pathophysiology of emergent acapsular group A streptococcus
监管串扰对新出现的无荚膜 A 族链球菌病理生理学的影响
  • 批准号:
    10301505
  • 财政年份:
    2021
  • 资助金额:
    $ 55.34万
  • 项目类别:
Impact of regulatory cross-talk on the pathophysiology of emergent acapsular group A streptococcus
监管串扰对新出现的无荚膜 A 族链球菌病理生理学的影响
  • 批准号:
    10449272
  • 财政年份:
    2021
  • 资助金额:
    $ 55.34万
  • 项目类别:
Project 2: Leveraging Metagenomics of the Microbiome to predict colonization/infection by antimicrobial-resistant pathogens
项目 2:利用微生物组的宏基因组学来预测耐药病原体的定植/感染
  • 批准号:
    10226288
  • 财政年份:
    2020
  • 资助金额:
    $ 55.34万
  • 项目类别:
Project 2: Leveraging Metagenomics of the Microbiome to predict colonization/infection by antimicrobial-resistant pathogens
项目 2:利用微生物组的宏基因组学来预测耐药病原体的定植/感染
  • 批准号:
    10614694
  • 财政年份:
    2020
  • 资助金额:
    $ 55.34万
  • 项目类别:
Contribution of catabolite control protein A to group A streptococcal virulence
分解代谢物控制蛋白 A 对 A 组链球菌毒力的贡献
  • 批准号:
    8300803
  • 财政年份:
    2011
  • 资助金额:
    $ 55.34万
  • 项目类别:
Contribution of catabolite control protein A to group A streptococcal virulence
分解代谢物控制蛋白 A 对 A 组链球菌毒力的贡献
  • 批准号:
    8107818
  • 财政年份:
    2011
  • 资助金额:
    $ 55.34万
  • 项目类别:
Contribution of catabolite control protein A to group A streptococcal virulence
分解代谢物控制蛋白 A 对 A 组链球菌毒力的贡献
  • 批准号:
    8479310
  • 财政年份:
    2011
  • 资助金额:
    $ 55.34万
  • 项目类别:
Contribution of catabolite control protein A to group A streptococcal virulence
分解代谢物控制蛋白 A 对 A 组链球菌毒力的贡献
  • 批准号:
    8692634
  • 财政年份:
    2011
  • 资助金额:
    $ 55.34万
  • 项目类别:
Contribution of catabolite control protein A to group A streptococcal virulence
分解代谢物控制蛋白 A 对 A 组链球菌毒力的贡献
  • 批准号:
    8871663
  • 财政年份:
    2011
  • 资助金额:
    $ 55.34万
  • 项目类别:

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