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.
As the rates of multi-drug resistant Neisseria gonorrhoeae (NG) continue to increase globally, determining the role of pharyngeal NG (pNG) infections, which are largely asymptomatic and are implicated in the emergence of antimicrobial resistance (AMR) in NG, has become a critical area of research to prevent further emergence of AMR. We propose an epidemiological study to define predictors of pNG infection, characterize AMR in pNG, and to adapt a single-cell molecular assay to improve characterization of AMR in pNG. Through the use of a multi- pronged approach combining clinical, microbiological, genomic, demographical and behavioral data, and novel diagnostics, this project addresses critical gaps in our understanding of pNG infections, AMR, and increases capacity building for development of diagnostics for AMR.
