Characterizing Antimicrobial Resistance in Pharyngeal Neisseria gonorrhoeae Infections and the Role of Commensal Neisseria Species

项目总结/摘要 淋病奈瑟菌（NG）感染是一个主要的公共卫生问题，由于全球出现 和耐多药NG的传播。咽NG（pNG）感染，主要是 无症状，是淋病持续传播的主要来源，并可能发挥重要作用 在NG中出现抗菌素耐药性（AMR）作为居民口咽粘膜 奈瑟氏菌属（CNspp）可作为AMR的储库，其可通过以下途径容易地被NG获得： 基因转移尽管pNG感染的重要性，但对流行病学的了解有限 耐抗生素pNG和缺乏诊断来表征pNG中的AMR。此指导 研究科学家职业发展（K01）提案将填补我们目前知识的关键空白 了解pNG感染，同时允许候选人通过研究提高技能， 培训和指导。此K01应用程序的具体培训重点包括：1）获得研究技能 2）通过流行病学研究获得定量统计分析方面的专业知识， 临床、微生物学、基因组和行为数据的三角测量; 3）获得基因组方面的培训 分析和生物信息学;以及4）为成功的学术研究开发额外的专业技能 研究生涯。为了解决pNG感染知识的差距，候选人提出了K01 研究涉及与增强型淋球菌抗菌药物合作的流行病学研究 乌干达坎帕拉的监测项目（EGASP）， pNG感染以前没有定义。本研究将：1）招募EGASP参与者， pNG高风险的尿道炎，2）收集咽部样品、临床、人口统计学和行为数据 3）与尿道NG（uNG）相比，定义pNG中的AMR，4）鉴定pNG感染的预测因子， 低收入国家的耐药性pNG（目标1），5）比较 pNG和uNG中的AMR，以及，6）描述AMR决定簇和AMR嵌合体的类型和频率 等位基因（Aim 2）。该项目还将测试单细胞微流控平台是否适用于 NG中AMR出现的表征和pNG中AMR检测的改进（目的3）。 本K01研究项目的目标和培训目标将通过以下指导来实现： 经验丰富的导师团队，在基础和转化研究方面有着出色的业绩记录， 专业知识的互补领域。K01奖将为候选人提供必要的培训 并指导成为STI转化研究的独立调查员。

PROJECT SUMMARY/ABSTRACT Neisseria gonorrhoeae (NG) infections are a major public health concern due to the global emergence and spread of multi-drug resistant NG. Pharyngeal NG (pNG) infections, which are primarily asymptomatic, are a major source of sustained gonorrhea transmission and may play an important role in the emergence of antimicrobial resistance (AMR) in NG as resident oropharyngeal commensal Neisseria species (CNspp) can serve as a reservoir for AMR, which can be easily acquired by NG through gene transfer. Despite the importance of pNG infections, there is limited knowledge on the epidemiology of antimicrobial-resistant pNG and a lack of diagnostics to characterize AMR in pNG. This Mentored Research Scientist Career Development (K01) proposal will fill critical gaps in knowledge in our current understanding of pNG infections while allowing the candidate to enhance his skillset through research, training, and mentoring. The specific training foci of this K01 application include: 1) to gain research skills in epidemiological studies; 2) to obtain expertise in quantitative statistical analysis through the triangulation of clinical, microbiological, genomic, and behavioral data; 3) to acquire training in genome analysis and bioinformatics; and 4) to develop additional professional skills for a successful academic research career. To address the gap in knowledge in pNG infections, the candidate's proposed K01 research involves an epidemiological study in collaboration with the Enhanced Gonococcal Antimicrobial Surveillance Program (EGASP) in Kampala, Uganda, where the epidemiology of antimicrobial-resistant pNG infections has not been previously defined. This study will: 1) recruit EGASP participants with urethritis at high risk for pNG, 2) collect pharyngeal samples, clinical, demographic, and behavioral data to 3) define AMR in pNG in comparison to urethral NG (uNG), 4) identify predictors of pNG infections and antimicrobial-resistant pNG in a low-income country (Aim 1), 5) compare the genomic epidemiology of AMR in pNG and uNG, and, 6) describe the type and frequency of AMR determinants and AMR mosaic alleles (Aim 2). This project will also test whether a single-cell microfluidic platform could be adapted for the characterization of the emergence of AMR in NG and improved detection of AMR in pNG (Aim 3). The objectives of this K01 research project and training goals will be achieved through guidance from a team of experienced mentors with outstanding track records in basic and translational research and with complementary areas of expertise. The K01 award will provide the candidate with the necessary training and mentoring to become an independent investigator in STI translational research.