Genomic epidemiology of Neisseria gonorrhoeae with elevated MICs to cefixime

头孢克肟 MIC 升高的淋病奈瑟菌的基因组流行病学

• 批准号: 8862369
• 负责人: Yonatan H Grad
• 金额: $ 17.64万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-15 至 2016-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8862369
• 关键词: Address; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Antimicrobial susceptibility; Arthritis; Azithromycin; Biology; Case Mixes; Cefixime; Ceftriaxone; Centers for Disease Control and Prevention (U.S.); Cephalosporin Resistance; Cephalosporins; Characteristics; Clinical; Collaborations; Communicable Diseases; Data Set; Diagnosis; Diagnostic; Disease Notification; Dose; Drosophila chb protein; Epidemiology; Fluoroquinolones; Foundations; Future; Genes; Genomics; Geographic Locations; Geography; Goals; Gonorrhea; HIV; Host Defense; Human; Individual; Infection; Infectious Disease Epidemiology; Infertility; Injectable; Institutes; Investigation; Lead; Location; Massachusetts; Mentorship; Molecular; Molecular Epidemiology; Nature; Neisseria gonorrhoeae; Oral; Orchitis; Patients; Pelvic Inflammatory Disease; Penicillins; Phylogeny; Physicians; Plasmids; Population; Population Biology; Population Heterogeneity; Predisposition; Preparation; Prevalence; Public Health; Public Health Schools; Reporting; Research; Research Personnel; Research Project Grants; Resistance; Risk Factors; Sampling; Sampling Studies; Scientist; Sequence Analysis; Sex Orientation; Single Nucleotide Polymorphism; Site; Surveillance Program; Swab; Synteny; Tetracyclines; Training; Treatment Protocols; Trust; United States; Urethritis; Woman; Work; career; career development; co-infection; demographics; disorder prevention; genome sequencing; insight; men; microbial; novel diagnostics; novel therapeutics; pathogen; professor; programs; public health intervention; success; therapy development; transmission process

DESCRIPTION (provided by applicant): This proposal presents a five-year research career development program in the study of Neisseria gonorrhoeae biology and epidemiology. The candidate is training in Infectious Diseases. The outlined proposal will provide training in the us of whole-genome sequence analysis and population genomics in preparation for a career as an independent physician-scientist integrating microbial sequence analysis and epidemiology of infectious diseases. The work will be conducted under the mentorship of Marc Lipsitch, Professor of Epidemiology and Director of the Center for Communicable Disease Dynamics at the Harvard School of Public Health, and will be pursued in collaboration with the Center for Disease Control and Prevention and the Wellcome Trust Sanger Institute. N. gonorrhoeae, the causative agent of gonorrhea, has developed antibiotic resistance to each of the first line antibiotics used to treat it. With the spread of resistance to ceftriaxone, a brod-spectrum cephalosporin, no treatment regimen remains that is cheap, single dose, well tolerated, and effective. In this proposal, the applicant aims to address fundamental questions about the emergence and spread of antibiotic resistant gonococcus, here focusing on isolates with elevated MICs to cefixime, an oral broad-spectrum cephalosporin. In collaboration with the Center for Disease Control and Prevention Gonococcal Isolate Surveillance Program and the Wellcome Trust Sanger Institute, the proposed work uses genomic epidemiological approaches combining large-scale whole-genome sequencing and epidemiology to explore whether isolates with elevated MICs to cefixime from across the United States are clonal (specific aim 1), how this diversity compares to the expected greater diversity in cefixime susceptible isolates matched by geography and demographic characteristics (specific aim 2), and to what extent differing geographic regions and networks harbor segregated gonococcal lineages (specific aim 3). Further, using a set of samples from the Massachusetts Department of Public Health, the proposed work will investigate the extent of mixed gonococcal infections, the risk factors for mixed infection, and the diversity of lineages in cases of mixed infection (specific aim 4). Detailed understanding of the emergence, spread, and underlying genotypic diversity of antibiotic resistance in gonococcus will help guide public health interventions and development of novel diagnostic and therapeutic strategies. RELEVANCE: Over 300,000 cases of gonorrhea are diagnosed annually in the United States, making it the second most reported of infectious diseases. While since the start of the antibiotic era treatment has been straightforward, Neisseria gonorrhoeae, the causative agent of gonorrhea, has become sequentially resistant to all the first line antibiotics that have been used to treat it, including now resistance to broad-spectrum cephalosporins. The main goal of this research project is to understand more about how antibiotic resistance emerges and spreads through the population and the biology of N. gonorrhoeae, thereby providing insights to help guide public health interventions, diagnostic approaches, and treatment regimens.

描述（由申请人提供）：本申请为淋病奈瑟菌生物学和流行病学研究的五年研究生涯发展计划。这位候选人正在接受传染病方面的培训。概述的建议将在美国提供全基因组序列分析和人口基因组学方面的培训，为成为一名独立的医生兼科学家做好准备，将微生物序列分析和传染病流行病学结合起来。这项工作将在哈佛大学公共卫生学院流行病学教授兼传染病动力学中心主任Marc Lipsitch的指导下进行，并将与疾病控制和预防中心以及威康信托基金会桑格研究所合作。

项目成果

Deep sequencing of RSV from an adult challenge study and from naturally infected infants reveals heterogeneous diversification dynamics.

• DOI: 10.1016/j.virol.2017.07.017
• 发表时间: 2017-10
• 期刊: Virology
• 影响因子: 3.7
• 作者: Lau JW;Kim YI;Murphy R;Newman R;Yang X;Zody M;DeVincenzo J;Grad YH
• 通讯作者: Grad YH