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

项目摘要/摘要 由于全球出现淋病奈瑟菌(NG)感染，是一个主要的公共卫生问题 和多重耐药NG的传播。咽新城疫(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 作为口咽共生菌的NG出现抗菌素耐药性(AMR) 奈瑟氏菌(CNspp)可作为AMR的储存库，NG可通过以下途径很容易获得AMR 基因转移。尽管PNG感染很重要，但关于流行病学的知识有限 存在耐药的PNG，缺乏诊断来确定PNG中AMR的特征。这位导师 研究科学家职业发展(K01)提案将填补我们目前在知识方面的关键空白 对巴新病毒感染的了解，同时允许候选人通过研究提高自己的技能， 培训和指导。K01应用程序的具体培训重点包括：1)获取研究技能 流行病学研究；2)通过以下途径获得定量统计分析的专业知识 临床、微生物、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)为成功的学术人员培养额外的专业技能 研究生涯。为了解决在PNG感染方面的知识差距，候选人提出的K01 研究涉及与增强型淋球菌抗菌剂合作的流行病学研究 乌干达坎帕拉监测计划(EGASP)，那里的抗菌素耐药性流行病学 PNG感染以前没有被定义过。这项研究将：1)招募EGASP参与者 尿道炎是PNG的高危人群，2)收集咽部样本、临床、人口统计学和行为数据 为了3)确定PNG中的AMR与尿路NG(Ung)的比较，4)确定PNG感染的预测因素，以及 低收入国家的抗菌素耐药性PNG(目标1)，5)比较 PNG和Ung中的AMR，以及，6)描述AMR决定因素和AMR嵌合体的类型和频率 等位基因(目标2)。该项目还将测试单细胞微流控平台是否可以用于 NG中AMR出现的特征和改进PNG中AMR的检测(目标3)。 K01研究项目的目标和培训目标将通过 经验丰富的导师团队，在基础研究和翻译研究方面有出色的记录，并具有 相互补充的专业领域。K01奖将为候选人提供必要的培训 并指导成为STI翻译研究的独立研究员。

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.