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

咽部淋病奈瑟菌感染的抗菌药物耐药性特征及共生奈瑟菌物种的作用

• 批准号: 10656295
• 负责人: Johan Humberto Melendez
• 金额: $ 13.07万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-22 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10656295
• 关键词: Address; Antibiotics; Antimicrobial Resistance; Antimicrobial susceptibility; Area; Azithromycin; Basic Science; Behavioral; Bioinformatics; Biological; Biological Assay; Ceftriaxone; Cells; Ciprofloxacin; Clinical; Clinical Data; Collaborations; Data; Detection; Developing Countries; Development; Diagnostic; Drug-resistant Neisseria Gonorrhoeae; Epidemiology; Exhibits; Frequencies; Future; Gene Transfer; Genetic; Genitourinary system; Genomics; Goals; Gonorrhea; HIV; Heterosexuals; Horizontal Gene Transfer; In Vitro; Infection; Knowledge; Mediating; Mentored Research Scientist Development Award; Mentors; Methods; Microfluidics; Molecular; Molecular Epidemiology; Monitor; Morbidity - disease rate; Multi-Drug Resistance; Neisseria; Neisseria cinerea; Neisseria gonorrhoeae; Oral; Oropharyngeal; Participant; Penicillins; Performance; Pharyngeal structure; Play; Prevention strategy; Public Health; Public Health Practice; Recommendation; Records; Reporting; Research; Research Personnel; Research Project Grants; Research Training; Resistance; Resistance development; Resistance profile; Resistance to infection; Resource-limited setting; Risk; Role; Sampling; Scientist; Sexually Transmitted Diseases; Source; Specificity; Statistical Data Interpretation; Surveillance Program; Testing; Tetracyclines; Training; Translational Research; Treatment Failure; Uganda; United States; Urethra; Urethritis; Visit; World Health Organization; antimicrobial; behavior prediction; career; career development; clinical predictors; clinically relevant; cross reactivity; detection assay; emerging antimicrobial resistance; epidemiologic data; epidemiology study; experience; experimental study; genome analysis; genome sequencing; genomic data; genomic epidemiology; high risk; improved; low income country; male; men; men who have sex with men; mosaic variant; novel; novel diagnostics; patient oriented research; pilot test; prevent; programs; recruit; skills; transmission process; trend; whole genome

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.

项目总结/文摘