The sexually transmitted disease gonorrhea, caused by Neisseria gonorrhoeae, continues to be a significant source of morbidity in the United States and around the world. Not only does it disproportionately affect certain minority populations (Black, non-Hispanic), but infects at rates >200 per 100,00 in five of the southeastern states. There remains no vaccine and the antibiotics that have been successfully used to treat this disease over the years have become ineffective one after another The CDC recommended treatment for gonococcal infections is now limited to a single class of drug, cephalosporins. The long-term goal of this project is to provide novel means to prevent this infection through interfering with the ability of a pilus accessory protein designated PilC, to interact with human cells. Because the PilC acts early in the infectious process we posit that interfering with its action could avert all the downstream steps of infection, thereby preventing infection. To accomplish this interference we need to better understand what parts of this large protein are involved in the act of adherence to human cells. To that end we will develop specific antibodies, mutations, and peptides that interfere with PilC-mediated adherence. We will develop a three-dimensional structural understanding of PilC that will guide our efforts to interfere with its adherence functions. We will establish PilC critical role in initiating infections using the experimental human infection model and investigate the significance gonococci maintaining two independent copies of the pilC gene.
Gonorrhoea infects more than an estimated 500,000 Americans annually. Antibiotics used to treat this infection continue to become ineffective because of bacterial resistance. The long-term goal of this project is to develop novel means of preventing gonococcal infection.
|Kissinger, Patricia J; White, Scott; Manhart, Lisa E et al. (2016) Azithromycin Treatment Failure for Chlamydia trachomatis Among Heterosexual Men With Nongonococcal Urethritis. Sex Transm Dis 43:599-602|
|Kandler, Justin L; Acevedo, Rosuany VÃ©lez; Dickinson, Mary Kathryne et al. (2016) The genes that encode the gonococcal transferrin binding proteins, TbpB and TbpA, are differentially regulated by MisR under iron-replete and iron-depleted conditions. Mol Microbiol 102:137-51|
|Kandler, Justin L; Holley, Concerta L; Reimche, Jennifer L et al. (2016) The MisR Response Regulator Is Necessary for Intrinsic Cationic Antimicrobial Peptide and Aminoglycoside Resistance in Neisseria gonorrhoeae. Antimicrob Agents Chemother 60:4690-700|
|Woolf-King, Sarah E; Muyindike, Winnie; Hobbs, Marcia M et al. (2016) Vaginal Prostate Specific Antigen (PSA) Is a Useful Biomarker of Semen Exposure Among HIV-Infected Ugandan Women. AIDS Behav :|
|Scheidell, Joy D; Lejuez, Carl W; Golin, Carol E et al. (2016) Borderline Personality Disorder Symptom Severity and Sexually Transmitted Infection and HIV Risk in African American Incarcerated Men. Sex Transm Dis 43:317-23|
|Samo, Melissa; Choudhary, Neelima R; Riebe, Kristina J et al. (2016) Immunization with the Haemophilus ducreyi trimeric autotransporter adhesin DsrA with alum, CpG or imiquimod generates a persistent humoral immune response that recognizes the bacterial surface. Vaccine 34:1193-200|
|Khan, M R; Golin, C E; Friedman, S R et al. (2015) STI/HIV Sexual Risk Behavior and Prevalent STI Among Incarcerated African American Men in Committed Partnerships: The Significance of Poverty, Mood Disorders, and Substance Use. AIDS Behav 19:1478-90|
|Unemo, Magnus; Shafer, William M (2015) Future treatment of gonorrhea--novel emerging drugs are essential and in progress? Expert Opin Emerg Drugs 20:357-60|
|Cash, Devin R; Noinaj, Nicholas; Buchanan, Susan K et al. (2015) Beyond the Crystal Structure: Insight into the Function and Vaccine Potential of TbpA Expressed by Neisseria gonorrhoeae. Infect Immun 83:4438-49|
|Gallo, Maria F; Warner, Lee; Hobbs, Marcia M et al. (2015) Differences in misreporting of sexual behavior over time: implications for HIV trials. Sex Transm Dis 42:160-1|
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