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.
|Rice, Cara E; Gallo, Maria F; Hobbs, Marcia M et al. (2014) Prostate-specific antigen is unlikely to be a suitable biomarker of semen exposure from recent unprotected receptive anal intercourse in men who have sex with men. Sex Transm Dis 41:377-9|
|Packiam, Mathanraj; Yedery, Roshan D; Begum, Afrin A et al. (2014) Phosphoethanolamine decoration of Neisseria gonorrhoeae lipid A plays a dual immunostimulatory and protective role during experimental genital tract infection. Infect Immun 82:2170-9|
|Jerse, Ann E; Bash, Margaret C; Russell, Michael W (2014) Vaccines against gonorrhea: current status and future challenges. Vaccine 32:1579-87|
|Vélez Acevedo, Rosuany N; Ronpirin, Chalinee; Kandler, Justin L et al. (2014) Identification of regulatory elements that control expression of the tbpBA operon in Neisseria gonorrhoeae. J Bacteriol 196:2762-74|
|Golparian, Daniel; Shafer, William M; Ohnishi, Makoto et al. (2014) Importance of multidrug efflux pumps in the antimicrobial resistance property of clinical multidrug-resistant isolates of Neisseria gonorrhoeae. Antimicrob Agents Chemother 58:3556-9|
|Fusco, William G; Choudhary, Neelima R; Routh, Patty A et al. (2014) The Haemophilus ducreyi trimeric autotransporter adhesin DsrA protects against an experimental infection in the swine model of chancroid. Vaccine 32:3752-8|
|Zhou, Xiyou; Gao, Xi; Broglie, Peter M et al. (2014) Hexa-acylated lipid A is required for host inflammatory response to Neisseria gonorrhoeae in experimental gonorrhea. Infect Immun 82:184-92|
|Kandler, Justin L; Joseph, Sandeep J; Balthazar, Jacqueline T et al. (2014) Phase-variable expression of lptA modulates the resistance of Neisseria gonorrhoeae to cationic antimicrobial peptides. Antimicrob Agents Chemother 58:4230-3|
|Unemo, Magnus; Shafer, William M (2014) Antimicrobial resistance in Neisseria gonorrhoeae in the 21st century: past, evolution, and future. Clin Microbiol Rev 27:587-613|
|Noinaj, Nicholas; Cornelissen, Cynthia Nau; Buchanan, Susan K (2013) Structural insight into the lactoferrin receptors from pathogenic Neisseria. J Struct Biol 184:83-92|
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