Elucidating transmission of plasmids harboring blaKPC among carbapenem-resistant Enterobacteriaceae using long-range sequencing

使用长程测序阐明携带 blaKPC 的质粒在碳青霉烯类耐药肠杆菌科细菌中的传播

基本信息

项目摘要

PROJECT SUMMARY/ABSTRACT: Rationale: Resistance to broad-spectrum carbapenem antibiotics has spread rapidly among Enterobacteriaceae since the early 1990s, posing an escalating threat to medical care. While Klebsiella pneumoniae comprise the majority of CRE in the United States, recent evidence suggests that CRE are rapidly diversifying. This reflects the ability of carbapenem resistance genes to spread to between different strains of Enterobacteriaceae via mobile genetic elements, particularly plasmids. Despite their important infection control implications, the mechanisms by which these plasmids spread have not been fully elucidated. Candidate: As an infectious diseases clinician with a masters’ degree in biostatistics, Dr. Angela Gomez-Simmonds’ previous publications characterize the clinical and molecular epidemiology of CRE. Formal training in advanced bioinformatics and genomic epidemiology will be critical for the completion of the proposed research and the advancement of her career. With primary mentor Dr. Anne-Catrin Uhlemann, she has assembled a multidisciplinary advisory team of experts to guide her training and research progress. Dr. Gomez-Simmonds’ long-term goal is to become an NIH-funded independent researcher using next-generation sequencing to understand links between the bacterial evolution, resistance mechanisms, and clinical epidemiology of multidrug-resistant Gram-negative nosocomial pathogens. Environment: The Uhlemann laboratory at Columbia University Medical Center (CUMC) has the microbiology and sequencing tools necessary to carry out the proposed research, as well as a large retrospective collection of CRE clinical isolates from diverse sites to perform genomic studies. CUMC has a strong track record of supporting the career development of young physician-scientists. Approach: We hypothesize that horizontal transfer of plasmids encoding blaKPC, the dominant carbapenem resistance gene in the United States, is an important contributor to the spread of CRE within hospitals. To overcome limitations in previous genomics studies using traditional sequencing platforms such as Illumina, we will perform long-range plasmid sequencing. Plasmid-mediated transmission of blaKPC will be characterized through three aims. In Aim 1 we will systematically assess the contribution of horizontal transfer to the spread of CRE in a large retrospective collection of CRE isolates collected between 2009-2016. In Aim 2 we will perform a case-control-control study to assess unique clinical risk factors associated with horizontal transfer versus clonal spread; a third control group will consist of CRE-negative patients. In Aim 3 we will determine whether hospital environmental surfaces such as sink drains are reservoirs for blaKPC- harboring plasmids. Phylogenetic analyses will be used to assess links between plasmid sequences from clinical and environmental CRE and published genomes. In addition to elucidating the role of plasmids in the diversification and spread of CRE, this research may contribute to the integration of long-range sequencing in effective infection surveillance and control protocols to account for plasmid-mediation CRE transmission.
项目总结/摘要: 理由:对广谱碳青霉烯类抗生素的耐药性已迅速蔓延, 肠杆菌科自20世纪90年代初以来,对医疗保健的威胁不断升级。而克雷伯氏菌 肺炎构成了美国大部分的CRE,最近的证据表明,CRE是迅速 多样化这反映了碳青霉烯耐药基因在不同菌株之间传播的能力。 肠杆菌科通过移动的遗传元件,特别是质粒。尽管他们的重要感染控制 这些质粒传播的机制尚未完全阐明。候选人: 安吉拉·戈麦斯·西蒙兹博士是一位传染病临床医生,拥有生物统计学硕士学位, 出版物描述了CRE的临床和分子流行病学特征。高级正规培训 生物信息学和基因组流行病学将是完成拟议的研究和 她的职业生涯的进步。与主要导师Anne-Catrin Uhlemann博士一起,她组建了一个 多学科的专家咨询小组,以指导她的培训和研究进展。戈麦斯-西蒙兹博士 长期目标是成为NIH资助的独立研究人员,使用下一代测序技术, 了解细菌进化,耐药机制和临床流行病学之间的联系, 多重耐药革兰氏阴性医院病原体。环境:Uhlemann实验室 哥伦比亚大学医学中心(Columbia University Medical Center,简称CDC)拥有携带所需的微生物学和测序工具, 提出了拟议的研究,以及从不同地点收集的大量CRE临床分离株 进行基因组研究。在支持年轻人的职业发展方面, 物理科学家方法:我们假设编码blaKPC的质粒的水平转移, 在美国,显性碳青霉烯耐药基因是CRE传播的重要因素 在医院内。为了克服以前使用传统测序平台进行基因组学研究的局限性, 例如Illumina,我们将进行长距离质粒测序。质粒介导的blaKPC传播将 通过三个目标来描述。在目标1中,我们将系统地评估横向 在2009 - 2016年期间收集的大量CRE分离株的回顾性收集中转移到CRE的传播。 在目标2中,我们将进行一项病例-对照-对照研究,以评估与下列因素相关的独特临床风险因素: 水平转移与克隆扩散;第三个对照组将由CRE阴性患者组成。目标3 我们将确定医院环境表面(如水槽排水沟)是否是blaKPC的储存库- 携带质粒。系统发育分析将用于评估来自 临床和环境CRE和已发表的基因组。除了阐明质粒在细胞中的作用外, CRE的多样化和传播,这项研究可能有助于整合远程测序, 有效的感染监测和控制方案,以解决质粒介导的CRE传播问题。

项目成果

期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Intestinal Dysbiosis and Risk of Posttransplant Clostridioides difficile Infection in a Longitudinal Cohort of Liver Transplant Recipients.
肝移植受者纵向队列中的肠道菌群失调和移植后艰难梭菌感染的风险。
  • DOI:
    10.1128/msphere.00361-22
  • 发表时间:
    2022-10-26
  • 期刊:
  • 影响因子:
    4.8
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Angela Gomez-Simmonds其他文献

Angela Gomez-Simmonds的其他文献

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{{ truncateString('Angela Gomez-Simmonds', 18)}}的其他基金

Elucidating transmission of plasmids harboring blaKPC among carbapenem-resistant Enterobacteriaceae using long-range sequencing
使用长程测序阐明携带 blaKPC 的质粒在碳青霉烯类耐药肠杆菌科细菌中的传播
  • 批准号:
    10057217
  • 财政年份:
    2018
  • 资助金额:
    $ 19.47万
  • 项目类别:

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